Sample records for occupancy prevents macrophage

  1. Prevention of occupational dermatitis.

    PubMed

    Sartorelli, P; Kezic, S; Larese Filon, F; John, S M

    2011-01-01

    Occupational dermatitis is among the most frequent occupational diseases. Dermal exposure risk affects many professional categories such as healthcare workers, hairdressers, bakers, cleaning and kitchen employees. The economical burden of occupational dermatitis (OD) is huge (greater than 5 billion Euro per year in Europe), comprising direct costs (treatment, compensation), as well as indirect costs due to sick leave and lack of productivity. A scientifically based preventive program consisting of skin protection during work, cleaning and skin care after work has generally been recommended to prevent occupational contact dermatitis. However the rate of reported occupational skin diseases seems unchanged in the recent years. In cases of impaired skin condition the secondary prevention (i.e. therapeutic treatment by dermatologists and health-educational intervention seminars) is fundamental. For cases of occupational dermatoses in which these outpatient prevention measures are not successful, interdisciplinary inpatient rehabilitation measures have been developed (tertiary individual prevention). In the past years, various pilot-concepts to improve occupational dermatitis prevention have been successfully put into practice focussing on interdisciplinary (dermatological and educational) skin protection training programmes for high-risk professions. Currently a multi-step intervention approach is implemented which is aiming at offering quick preventive help at all levels of severity of occupational contact dermatitis. Recent data reveals that there are reliable evidence-based options for multidisciplinary prevention and patient management of occupational dermatitis using a combined approach by a network of clinics, practices and statutory social insurance bodies. At this stage, it seemed reasonable to form a European joint initiative for skin prevention. Recently a European network of preventive dermatology (European Initiative for the Prevention of Occupational Skin

  2. Occupational cancer in Britain. Preventing occupational cancer.

    PubMed

    Chen, Yiqun; Osman, John

    2012-06-19

    Although only a relatively small proportion of cancer is attributable to occupational exposure to carcinogenic agents, the estimated number of deaths due to occupational cancer is high when compared to other deaths due to work-related ill health and injury. However, risk from occupational exposure to carcinogens can be minimised through proportionate but effective risk management. The Health and Safety Executive (HSE) is the regulator of workplace health and safety in Great Britain. As part of its aim to reduce ill health arising from failures to control properly exposure to hazards at work, HSE commissioned the research presented elsewhere in this supplement to enable it to identify priorities for preventing occupational cancer. The research has shown that occupational cancer remains a key health issue and that low-level exposure of a large number of workers to carcinogens is important. The finding that a small number of carcinogens have been responsible for the majority of the burden of occupational cancer provides key evidence in the development of priorities for significant reduction of occupational cancer. Although the research presented in this supplement reflects the consequences of past exposures to carcinogens, occupational cancer remains a problem. The potential for exposure to the agents considered in this research is still present in the workplace and the findings are relevant to prevention of future disease. In this article, the principle approaches for risk reduction are described. It provides supporting information on some of the initiatives already being undertaken, or those being put in place, to reduce occupational cancer in Great Britain. The need also for systematic collection of exposure information and the importance of raising awareness and changing behaviours are discussed.

  3. Occupational Stress: Preventing Suffering, Enhancing Wellbeing.

    PubMed

    Quick, James Campbell; Henderson, Demetria F

    2016-04-29

    Occupational stress is a known health risk for a range of psychological, behavioral, and medical disorders and diseases. Organizations and individuals can mitigate these disorders through preventive stress management and enhanced wellbeing. This article addresses, first, the known health risk evidence related to occupational stress; second, the use of preventive stress management in organizations as the framework for intervention; and third, the emerging domain of enhancing wellbeing, which strengthens the individual. Premature death and disability along with chronic suffering from occupational stress are not inevitable, despite being known outcome risks.

  4. [Preventing occupational eye trauma (Geneva, Switzerland)].

    PubMed

    Ngondi, C Emole; Chastonay, P; Dosso, A

    2010-01-01

    Occupational eye trauma causes injuries with often serious socioprofessional, medical-legal, and economic consequences, not only for workers themselves, but also for employers. In spite of today's legislation and the efforts to encourage prevention, the frequency of occupational ocular accidents remains relatively high despite how easy it is to protect the eyes. In this study, the reasons that these accidents persist despite the progress made in preventive measures was investigated. From January to July 2005, we analyzed the parameters related to 175 occupational eye injuries. All patients agreed to take part in this study, which was carried out in the emergency unit of the Ophthalmology Clinic at Geneva University Hospital. Additional data was collected in companies. Construction workers were the most exposed (41.1%). The activity with the greatest risk was grinding (19.4%). The most affected structure of the eye was the cornea (84%), 72.6% patients were not equipped with ocular protection at the time of the accident, and 17.4% wore poorly adapted eye protection. This can be explained by negligence, lack of awareness, etc. Overall, workers, employers, and the legislation in force are all responsible. Our results are comparable with those found in the literature, with certain particularities because heavy industry was underrepresented in our sample. Analysis of the law on the prevention of occupational accidents and diseases shows that the worker is not sufficiently aware of his responsibilities. To our knowledge, the legal aspects treated herein have not been studied. As done in certain studies, we emphasize the importance of preventive ophthalmologic examinations as well as improvement of both working conditions and worker awareness in the workplace. Primary prevention must be reinforced. Information campaigns within the workplace aimed at workers and revision of the laws on occupational safety are some of the recommendations that are proposed to control

  5. Etidronate prevents dystrophic cardiac calcification by inhibiting macrophage aggregation.

    PubMed

    Bauer, Carolin; le Saux, Olivier; Pomozi, Viola; Aherrahrou, Redouane; Kriesen, Rene; Stölting, Stephanie; Liebers, Annett; Kessler, Thorsten; Schunkert, Heribert; Erdmann, Jeanette; Aherrahrou, Zouhair

    2018-04-11

    Cardiovascular calcification is associated with high risk of vascular disease. This involves macrophage infiltration of injured vascular tissue and osteoclast-related processes. Splenic monocytes from mice, that are predisposed (C3H) or resistant (B6) to calcification, were isolated and differentiated in vitro with M-CSF to generate macrophages, which aggregate to form multinucleated (MN) cells in the presence of RANKL. MN cell formation was significantly decreased in monocytes from resistant compared with calcifying mice. Conditioned media from C3H macrophages strongly induced calcification in vitro. However, medium from B6 macrophages inhibited calcification. An increase in ICAM-1 was detected in conditioned media from C3H macrophages compared with B6, suggesting a key role for this molecule in calcification processes. Due to natural genetic loss of Abcc6, the causal gene for cardiac calcification, C3H mice have reduced plasma levels of inorganic pyrophosphate (PPi), a potential calcification inhibitor. Supplementation of C3H mice with PPi or Etidronate prevented but did not completely reverse cardiac calcification. Our data provide strong evidence of the pathogenesis of macrophages and MNs during tissue calcification and suggest PPi or its analogue Etidronate as a potential inhibitor of MN formation and calcification. Furthermore, the adhesion molecule ICAM-1 was shown to play a key role in calcification.

  6. Occupational Stress: Preventing Suffering, Enhancing Wellbeing †

    PubMed Central

    Quick, James Campbell; Henderson, Demetria F.

    2016-01-01

    Occupational stress is a known health risk for a range of psychological, behavioral, and medical disorders and diseases. Organizations and individuals can mitigate these disorders through preventive stress management and enhanced wellbeing. This article addresses, first, the known health risk evidence related to occupational stress; second, the use of preventive stress management in organizations as the framework for intervention; and third, the emerging domain of enhancing wellbeing, which strengthens the individual. Premature death and disability along with chronic suffering from occupational stress are not inevitable, despite being known outcome risks. PMID:27136575

  7. [Prevention of occupational dermatitis in an international perspective].

    PubMed

    Montomoli, L; Paolucci, V; Sartorelli, P

    2012-01-01

    Occupational dermatitis (OD) have always been a significant part of the occupational disease with huge social and economic costs. Traditionally, the standard program of OD prevention takes place in the three phases of protection, cleansing and use of emollient creams and other products able to improve the cutaneous trophism (skincare) at the end of the shiftwork. However, in countries like Germany where protection measures and skincare were widespread, there was not a simultaneous decrease in the OD. In recent years pilot programs for the prevention of OD have been implemented with positive results. In particular the integrated approach that includes three steps of primary, secondary and tertiary prevention (Osnabrueck model) is of great interest. Primary prevention is represented by introduction of technical regulations, pre-employment counselling and specific initiatives to promote health (healthy skin campaign). In the case of initial/minor OD, secondary prevention is accomplished through the dermatological treatment of the patient and 1-2 days outpatient education initiatives/skin protection training. In severe cases of individual OD, tertiary prevention involves the hospitalization of the patient in a dermatology department. In 2009 the European network EPOS (European Initiative for the Prevention of Occupational Skin Diseases) of preventive dermatology has been organized basing on the integrated approach of primary, secondary and tertiary prevention.

  8. Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate

    PubMed Central

    Villa-Bellosta, Ricardo; Hamczyk, Magda R.; Andrés, Vicente

    2017-01-01

    Purpose Phosphorus is an essential nutrient involved in many pathobiological processes. Less than 1% of phosphorus is found in extracellular fluids as inorganic phosphate ion (Pi) in solution. High serum Pi level promotes ectopic calcification in many tissues, including blood vessels. Here, we studied the effect of elevated Pi concentration on macrophage polarization and calcification. Macrophages, present in virtually all tissues, play key roles in health and disease and display remarkable plasticity, being able to change their physiology in response to environmental cues. Methods and results High-throughput transcriptomic analysis and functional studies demonstrated that Pi induces unpolarized macrophages to adopt a phenotype closely resembling that of alternatively-activated M2 macrophages, as revealed by arginine hydrolysis and energetic and antioxidant profiles. Pi-induced macrophages showed an anti-calcifying action mediated by increased availability of extracellular ATP and pyrophosphate. Conclusion We conclude that the ability of Pi-activated macrophages to prevent calcium-phosphate deposition is a compensatory mechanism protecting tissues from hyperphosphatemia-induced pathologic calcification. PMID:28362852

  9. Work Disability Prevention: A Primer for Occupational Therapists.

    PubMed

    McDougall, Alicia; Nowrouzi-Kia, Behdin

    An estimated 313 million workplace accidents resulting in injury occur worldwide every year. Therefore, the burden of workplace injury and disability is present at the individual and the societal level and involves several stakeholders. There has been a shift in paradigm from workplace disability and injury treatment to workplace disability prevention. Occupational therapy practitioners are well positioned to address this multifaceted societal issue. Opening communication lines among stakeholders allows for a more holistic, collaborative, and comprehensive approach to disability, injury, and pain management. The positive results researchers have found at the individual level when using a holistic approach translate to benefits for all of the stakeholders involved. Occupational therapy practitioners may espouse a work disability prevention approach to reduce work disability rates and provide timely return-to-work outcomes for clients. The transition to the preventative model requires collaboration among stakeholders but would be beneficial to all stakeholders involved in the workplace. Copyright © 2017 by the American Occupational Therapy Association, Inc.

  10. Occupational Injury Prevention Research in NIOSH

    PubMed Central

    Stout, Nancy

    2010-01-01

    This paper provided a brief summary of the current strategic goals, activities, and impacts of the NIOSH (National Institute for Occupational Safety and Health) occupational injury research program. Three primary drivers (injury database, stakeholder input, and staff capacity) were used to define NIOSH research focuses to maximize relevance and impact of the NIOSH injury-prevention-research program. Injury data, strategic goals, program activities, and research impacts were presented with a focus on prevention of four leading causes of workplace injury and death in the US: motor vehicle incidents, falls, workplace violence, and machine and industrial vehicle incidents. This paper showcased selected priority goals, activities, and impacts of the NIOSH injury prevention program. The NIOSH contribution to the overall decrease in fatalities and injuries is reinforced by decreases in specific goal areas. There were also many intermediate outcomes that are on a direct path to preventing injuries, such as new safety regulations and standards, safer technology and products, and improved worker safety training. The outcomes serve as an excellent foundation to stimulate further research and worldwide partnership to address global workplace injury problems. PMID:22953170

  11. Joint occupational and environmental pollution prevention strategies: a model for primary prevention.

    PubMed

    Armenti, Karla; Moure-Eraso, Rafael; Slatin, Craig; Geiser, Ken

    2003-01-01

    Occupational and environmental health issues are not always considered simultaneously when attempting to reduce or eliminate hazardous materials from our environment. Methods used to decrease exposure to hazardous chemicals in the workplace often lead to increased exposure in the environment and to the community outside the workplace. Conversely, efforts to control emissions of hazardous chemicals into the environment often lead to increased exposure to the workers inside the plant. There are government regulations in place that ensure a safe work environment or a safe outside environment; however, there is little integration of both approaches when considering the public's health as a whole. This article examines some of the reasons behind this dichotomy, focusing on the regulatory and policy frameworks with respect to workplace and environment that have resulted in the inability of the Occupational Safety and Health Administration (OSHA) and the Environmental Protection Agency (EPA) to coordinate their efforts to protect public health. The components of the Pollution Prevention Act and its potential to serve as a model for integrating occupational and environmental health are discussed. Limitations regarding enforcement of pollution prevention, as well as its disconnection from the work environment are equally highlighted. The article finishes by examining the barriers to integrating the occupational and environmental health paradigms and the promotion of primary prevention in public health.

  12. Gaps in Workplace Education For Prevention of Occupational Skin Disease.

    PubMed

    Gupta, Tanya; Arrandale, Victoria H; Kudla, Irena; Holness, D Linn

    2018-02-13

    Occupational contact dermatitis (OCD) is a common occupational disease. Evidence suggests that education and training are effective prevention strategies. In spite of these known prevention strategies, workers continue to develop OCD. Little is reported regarding the actual training experience of workers. To examine the training experience of workers with contact dermatitis to identify areas for improvement. Participants were workers being assessed for contact dermatitis in an occupational health clinic. The anonymous survey collected demographics, workplace characteristics, and education and prevention practices. Approximately 80% reported general occupational health and safety training; however, only 49% reported skin-specific training (SST). For workers reporting SST, most received information regarding exposure avoidance, hand washing, and glove use. This content was reported as helpful by at least 50%. Workers who did not receive SST indicated the most important content would be warning signs of skin problems, how to avoid exposure and skin care while using gloves. While the study was anonymous and used self-reported of training experience, the study suggests there are gaps in skin protection training. Addressing these gaps may lead to improved prevention and reduction in OCD. © The Author(s) 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  13. Prevention and Early Detection of Occupational Cancers - a View of Information Technology Solutions.

    PubMed

    Davoodi, Somayeh; Safdari, Reza; Ghazisaeidi, Marjan; Mohammadzadeh, Zeinab; Azadmanjir, Zahra

    2015-01-01

    Thousands of people die each year from cancer due to occupational causes. To reduce cancer in workers, preventive strategies should be used in the high-risk workplace. The effective prevention of occupational cancer requires knowledge of carcinogen agents. Like other areas of healthcare industry, occupational health has been affected by information technology solutions to improve prevention, early detection, treatment and finally the efficiency and cost effectiveness of the healthcare system. Information technology solutions are thus an important issue in the healthcare field. Information about occupational cancer in information systems is important for policy makers, managers, physicians, patients and researchers; because examples that include high quality data about occupational cancer patients and occupational cancer causes are able to determine the worker groups which require special attention. As a result exposed workers who are vulnerable can undergo screening and be considered for preventive interventions.

  14. [Chronic migraine and work: occupational risks and prevention].

    PubMed

    Vicente-Herrero, M T; Ramírez Iñiguez de la Torre, M V; Capdevila García, L M; López-González, Á A; Terradillos García, M J

    2013-09-01

    Chronic migraine is a clinically difficult to manage primary headache which affects the quality of life of the patients. This impact is important in the occupational world, where along with the clinical aspects of the disease, the therapies used for the control of the symptoms or preventive aspects, must be assessed. The side effects of the drugs and the limitations associated with their symptoms are aspects to highlight in occupational health, especially in individual workplaces, where there is a high risk of work-related injuries. The medical officer must assess the occupational risks of particular importance in the progression of this disease, as well as preventive actions, within the ambit of the current Spanish legislation, that may be favorable for both the company and the worker. The coordinated medical intervention and knowledge of these occupational aspects can provide clinically relevant tools, andoccupational and social optimization in the use of available resources. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  15. [Development of knowledge, attitude and practice questionnaire on prevention and control of occupational diseases].

    PubMed

    Gao, Yuan; Feng, Yuchao; Wang, Min; Su, Yiwei; Li, Yanhua; Wang, Zhi; Tang, Shihao

    2015-04-01

    To develop the knowledge, attitude and practice questionnaire on the prevention and control of occupational diseases for occupational groups, and to provide a convenient and effective tool for the survey of knowledge, attitude, and behavior on the prevention and control of occupational diseases in occupational groups and the evaluation of intervention effect. The initial questionnaire which was evaluated by the experts was used to carry out a pre-survey in Guangzhou, China. The survey results were statistically analyzed by t test, identification index method, correlation analysis, and Cronbach's a coefficient method. And then the questionnaire was further modified, and the content of the questionnaire was determined finally. After modification, there were 18 items on knowledge, 16 items on attitude, and 12 items on behavior in the "Knowledge, attitude and practice questionnaire on the prevention and control of occupational diseases for enterprise managers"; there were 19 items on knowledge, 10 items on attitude, and 11 items on behavior in the "Knowledge, attitude and practice questionnaire on the prevention and control of occupational diseases for workers". The knowledge, attitude and practice questionnaire on the prevention and control of occupational diseases for occupational groups is developed successfully, and it is a convenient and effective tool for the survey of knowledge, attitude, and behavior on the prevention and control of occupational diseases in occupational groups and the evaluation of intervention effect.

  16. Inhibition of macrophage function prevents intestinal inflammation and postoperative ileus in rodents

    PubMed Central

    Wehner, Sven; Behrendt, Florian F; Lyutenski, Boris N; Lysson, Mariola; Bauer, Anthony J; Hirner, Andreas; Kalff, Jörg C

    2007-01-01

    muscularis macrophage network prevents postoperative ileus. PMID:16809419

  17. Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis

    PubMed Central

    Takeda, Yukiji; Costa, Sandra; Delamarre, Estelle; Roncal, Carmen; de Oliveira, Rodrigo Leite; Squadrito, Mario Leonardo; Finisguerra, Veronica; Deschoemaeker, Sofie; Bruyére, Françoise; Wenes, Mathias; Hamm, Alexander; Serneels, Jens; Magat, Julie; Bhattacharyya, Tapan; Anisimov, Andrey; Jordan, Benedicte F.; Alitalo, Kari; Maxwell, Patrick; Gallez, Bernard; Zhuang, Zhen W.; Saito, Yoshihiko; Simons, Michael; De Palma, Michele; Mazzone, Massimiliano

    2015-01-01

    PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage1–5. However, it is unknown whether PHD2 can influence arteriogenesis. Here we studied the role of PHD2 in collateral artery growth by using hindlimb ischaemia as a model, a process that compensates for the lack of blood flow in case of major arterial occlusion6–8. We show that Phd2 (also known as Egln1) haplodeficient (Phd2+/−) mice displayed preformed collateral arteries that preserved limb perfusion and prevented tissue necrosis in ischaemia. Improved arteriogenesis in Phd2+/− mice was due to an expansion of tissue-resident, M2-like macrophages9,10 and their increased release of arteriogenic factors, leading to enhanced smooth muscle cell (SMC) recruitment and growth. Both chronic and acute deletion of one Phd2 allele in macrophages was sufficient to skew their polarization towards a proarteriogenic phenotype. Mechanistically, collateral vessel preconditioning relied on the activation of canonical NF-κB pathway in Phd2+/− macrophages. These results unravel how PHD2 regulates arteriogenesis and artery homeostasis by controlling a specific differentiation state in macrophages and suggest new treatment options for ischaemic disorders. PMID:21983962

  18. [Dry eye syndrome. Occupational risk factors, valuation and prevention].

    PubMed

    Vicente-Herrero, M T; Ramírez-Iñiguez de la Torre, M V; Terradillos-García, M J; López González, Á A

    2014-03-01

    Dry eye syndrome in the workplace is associated with new ways of working, with increasing use of screens and electronic devices and environmental conditions encountered in modern office designs and other environments. Also affect occupational exposure to ionizing radiation, chemicals or atmospheric dust with increased ocular dryness. The study of pathophysiological aspects and laboral causality of the dry eye, must be to develop joint task in Occupational Health, Public Health in coordination with and responsible for the national health system, which would involve primary and secondary preventive measures more effective and proper diagnosis, control and monitoring of the disease, A better knowledge of occupational hazards and actions agreed and coordinated between occupational physicians, preventers, primary care physicians and specialist physicians, such as ophthalmology, will get results much more effective when earlier and optimize available resources. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  19. Case-control study on the prevention of occupational eye injuries.

    PubMed

    Ho, Chi-Kung; Yen, Ya-Lin; Chang, Cheng-Hsien; Chiang, Hung-Che; Shen, Ying-Ying; Chang, Po-Ya

    2008-01-01

    The risk factors for occupational eye injuries have never been published in Taiwan. We conducted a case-control study to analyze the differences among workers on their knowledge, attitude to and practice (KAP) of occupational accident prevention. In the study, a statistical model was also set up for predicting the occupational problem. Subjects, including 31 cases of work-related eye injuries and 62 controls, completed a structured questionnaire on KAP, which revealed that 80.6% and 62.7% of workers in the case and control groups, respectively, did not wear eye protection during work. Furthermore, we found that temporary employment (OR, 10.7; 95% CI, 3.03-36.16) and fewer than 10 years of education (OR, 4.44; 95% CI, 1.73-11.44) were the major risk factors for occupational eye injuries. In addition, we developed a logistic regression model with four predictors (temporary employment, education years less than 10, poor management of industrial health and safety in the workplace, and poor attitude towards accident prevention) for the occurrence of occupational eye injuries. In conclusion, in Taiwan, compulsory regulation of wearing eye protection during work, good education, management of work safety and hygiene and employee (especially temporary worker) commitment to safety and health are strongly recommended prevention strategies.

  20. [Prevention and regeneration of barrier disturbances in occupational dermatology].

    PubMed

    Schürer, Nanna Y; Schwanitz, Hans J

    2004-11-01

    Over the past 10 years primary, secondary and tertiary prevention of occupational skin disorders has been shown to be successful, documented with appropriate statistical methods. Interventional strategies are the main features of secondary and tertiary prevention, now well-established in occupational dermatology. Primary prevention is best accomplished by health education measures, both in the form on individual counseling and seminars. This overview reviews the scientific background of hand eczema with respect to barrier damage and repair and then considers the options for individualized and focused prevention. Special anatomical features of the interdigital space and palms, as well as functional disorders, such as palmar hyperhidrosis, are discussed. The importance of barrier regeneration is considered in light of the role of an acid pH, the epidermal calcium gradient and aspects of percutaneous absorption. The effects of anti-oxidants are considered, and new bioengineering methods which rely on physiologic measuring techniques are reviewed.

  1. [KAP research and intervention effects of health education on prevention and control of occupational diseases in occupational groups in Jinzhou, China].

    PubMed

    Wang, D H; Liu, X L; Quan, J K

    2016-04-20

    To investigate the current status of knowledge, attitude, and practice (KAP)on the prevention and control of occupational diseases in occupational groups in Jinzhou, China, and to evaluate the intervention effects of health education. Using the cluster random sampling method, 1000 workers who underwent occupational health examination in Jinzhou Center for Disease Control and Prevention from September 2014 to April 2015 were enrolled in this study. They were equally and randomly divided into intervention group and control group. The intervention group received health education for 6 months through bulletin board, promotion materials, expert lecture, Q&A session, and other relevant educational events. The questionnaire survey was performed before and after intervention. The control group received the questionnaire survey but not the health education. The overall awareness rate of prevention and control knowledge was 75.34% in 990 workers in Jinzhou, China. After the intervention, the intervention group had a significantly higher awareness rate of prevention and control knowledge than the control group (89.87%~98.86% vs 71.25%~80.82%, P<0.05); the intervention group had a significantly higher attitude accuracy for" whether occupational health examination is necessary or not" and " is willing to received the training on occupational health knowledge" than the control group(χ(2)=57.857, P<0.05; χ(2)=70.683, P<0.05); and the intervention group had a significantly higher rate of correct behavior for" whether help the business management personnel to carry out the prevention and control of occupational diseases or not" and"whether actively understand the occupational hazards of job" (χ(2)=102.186, P<0.05; χ(2)=91.159, P<0.05). Health education can significantly increase the awareness rate of prevention and control knowledge on occupational diseases in occupational groups in Jinzhou, China. However, the more structured and longterm comprehensive intervention is

  2. Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters.

    PubMed

    Hammerbeck, Christopher D; Brocato, Rebecca L; Bell, Todd M; Schellhase, Christopher W; Mraz, Steven R; Queen, Laurie A; Hooper, Jay W

    2016-07-15

    Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS. Hantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract, alveolar macrophages are

  3. Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters

    PubMed Central

    Hammerbeck, Christopher D.; Brocato, Rebecca L.; Bell, Todd M.; Schellhase, Christopher W.; Mraz, Steven R.; Queen, Laurie A.

    2016-01-01

    ABSTRACT Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS. IMPORTANCE Hantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract

  4. Prevention of occupational injuries: Evidence for effective good practices in foundries.

    PubMed

    Porru, Stefano; Calza, Stefano; Arici, Cecilia

    2017-02-01

    Occupational injuries are a relevant research and practical issue. However, intervention studies evaluating the effectiveness of workplace injury prevention programs are seldom performed. The effectiveness of a multifaceted intervention aimed at reducing occupational injury rates (incidence/employment-based=IR, frequency/hours-based=FR, severity=SR) was evaluated between 2008 and 2013 in 29 Italian foundries (22 ferrous; 7 non-ferrous; 3,460 male blue collar workers/year) of varying sizes. Each foundry established an internal multidisciplinary prevention team for risk assessment, monitoring and prevention of occupational injuries, involving employers, occupational physicians, safety personnel, workers' representatives, supervisors. Targets of intervention were workers, equipment, organization, workplace, job tasks. An interrupted time series (ITS) design was applied. 4,604 occupational injuries and 83,156 lost workdays were registered between 2003 and 2013. Statistical analysis showed, after intervention, a reduction of all injury rates (-26% IR, -15% FR, -18% SR) in ferrous foundries and of SR (-4%) in non-ferrous foundries. A significant (p=0.021) 'step-effect' was shown for IR in ferrous foundries, independent of secular trends (p<0.001). Sector-specific benchmarks for all injury rates were developed separately for ferrous and non-ferrous foundries. Strengths of the study were: ITS design, according to standardized quality criteria (i.e., at least three data points before and three data points after intervention; clearly defined intervention point); pragmatic approach, with good external validity; promotion of effective good practices. Main limitations were the non-randomized nature and a medium length post-intervention period. In conclusion, a multifaceted, pragmatic and accountable intervention is effective in reducing the burden of occupational injuries in small-, medium- and large-sized foundries. Practical Applications: The study poses the basis for

  5. Preventing occupational injury among police officers: does motivation matter?

    PubMed

    Chan, D K C; Webb, D; Ryan, R M; Tang, T C W; Yang, S X; Ntoumanis, N; Hagger, M S

    2017-08-01

    Injury prevention is an important issue for police officers, but the effectiveness of prevention initiatives is dependent on officers' motivation toward, and adherence to, recommended health and safety guidelines. To understand effects of police officers' motivation to prevent occupational injury on beliefs about safety and adherence to injury prevention behaviours. Full-time police officers completed a survey comprising validated psychometric scales to assess autonomous, controlled and amotivated forms of motivation (Treatment Self-Regulation Questionnaire), behavioural adherence (Self-reported Treatment Adherence Scale) and beliefs (Safety Attitude Questionnaire) with respect to injury prevention behaviours. There were 207 participants; response rate was 87%. Hierarchical multiple regression analyses demonstrated that autonomous motivation was positively related to behavioural adherence, commitment to safety and prioritizing injury prevention. Controlled motivation was a positive predictor of safety communication barriers. Amotivation was positively associated with fatalism regarding injury prevention, safety violation and worry. These findings are consistent with the tenets of self-determination theory in that autonomous motivation was a positive predictor of adaptive safety beliefs and adherence to injury prevention behaviours. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  6. Gender specific analysis of occupational diseases of the low back caused by carrying, lifting or extreme trunk flexion—use of a prevention index to identify occupations with high prevention needs

    PubMed Central

    Thiede, Markus; Liebers, Falk; Seidler, Andreas; Gravemeyer, Stefan; Latza, Ute

    2014-01-01

    Background Gender specific analysis of the occupational disease of the lumbar spine caused by carrying, lifting, or extreme trunk flexion in Germany (OD No.2108) with the aim to identify areas of focus for prevention and research with a prevention index (PI). Methods Data from the German Statutory Accident Insurance stratified by gender are shown. Results From 2002 until 2009 there were 2,877 confirmed cases of an OD No. 2108 (40.1% male and 59.1% female). The PI indicated the highest prevention need for female nursing/midwifery associate professionals and male building frame and related trades workers. Patient transfer and working in extremely bent posture were the most frequent exposures. Conclusions The identified occupations with high need for prevention among men come from nearly all major occupational groups whereas women cluster in occupational groups from the health and care sectors. Am. J. Ind. Med. 57:233–244, 2014. © 2013 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals, Inc. PMID:24243091

  7. Promoting prevention with economic arguments – The case of Finnish occupational health services

    PubMed Central

    Kankaanpää, Eila; Suhonen, Aki; Valtonen, Hannu

    2008-01-01

    Background Both social and ethical arguments have been used to support preventive occupational health services (OHS). During the 1990s it became more common to support political argumentation for occupational health and safety by converting the consequences of ill health at work into monetary units. In addition, OHS has been promoted as a profitable investment for companies, and this aspect has been used by OHS providers in their marketing. Our intention was to study whether preventive occupational health services positively influence a company's economic performance. Methods We combined the financial statements provided by Statistics Finland and employers' reimbursement applications for occupational health services (OHS) costs to the Social Insurance Institution. The data covered the years 1997, 1999 and 2001 and over 6000 companies. We applied linear regression analysis to assess whether preventive OHS had had a positive influence on the companies' economic performance after two or four years. Results Resources invested in preventive OHS were not positively related to a company's economic performance. In fact, the total cost of preventive OHS per turnover was negatively correlated to economic performance. Conclusion Even if OHS has no effect on the economic performance of companies, it may have other effects more specific to OHS. Therefore, we recommend that the evaluation of prevention in OHS should move towards outcome measures, such as sickness absence, disability pension and productivity, when applicable, both in occupational health service research and in practice at workplaces. PMID:18430218

  8. Environmental and occupational interventions for primary prevention of cancer: a cross-sectorial policy framework.

    PubMed

    Espina, Carolina; Porta, Miquel; Schüz, Joachim; Aguado, Ildefonso Hernández; Percival, Robert V; Dora, Carlos; Slevin, Terry; Guzman, Julietta Rodriguez; Meredith, Tim; Landrigan, Philip J; Neira, Maria

    2013-04-01

    Nearly 13 million new cancer cases and 7.6 million cancer deaths occur worldwide each year; 63% of cancer deaths occur in low- and middle-income countries. A substantial proportion of all cancers are attributable to carcinogenic exposures in the environment and the workplace. We aimed to develop an evidence-based global vision and strategy for the primary prevention of environmental and occupational cancer. We identified relevant studies through PubMed by using combinations of the search terms "environmental," "occupational," "exposure," "cancer," "primary prevention," and "interventions." To supplement the literature review, we convened an international conference titled "Environmental and Occupational Determinants of Cancer: Interventions for Primary Prevention" under the auspices of the World Health Organization, in Asturias, Spain, on 17-18 March 2011. Many cancers of environmental and occupational origin could be prevented. Prevention is most effectively achieved through primary prevention policies that reduce or eliminate involuntary exposures to proven and probable carcinogens. Such strategies can be implemented in a straightforward and cost-effective way based on current knowledge, and they have the added benefit of synergistically reducing risks for other noncommunicable diseases by reducing exposures to shared risk factors. Opportunities exist to revitalize comprehensive global cancer control policies by incorporating primary interventions against environmental and occupational carcinogens.

  9. 75 FR 4406 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Occupational...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-27

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Occupational Safety and Health Training Projects Grants, Request for Applications (RFA) 06-484; and Occupational Safety and Health Educational...

  10. Prevention through pre-review in occupational health and safety.

    PubMed Central

    Richter, E D; Kretzmer, D

    1980-01-01

    Occupational health problems have needlessly been produced at many worksites as a consequence of their not having been anticipated during design and construction. Pre-review may be an effective and efficient mechanism for preventive intervention in occupational health and safety. Legal and administrative precedents are cited from the United States and other countries. Proposals are presented, with Israel as an example, which aim to implement the principle of pre-review. PMID:7352610

  11. Triamcinolone acetonide activates an anti-inflammatory and folate receptor-positive macrophage that prevents osteophytosis in vivo.

    PubMed

    Siebelt, Michiel; Korthagen, Nicoline; Wei, Wu; Groen, Harald; Bastiaansen-Jenniskens, Yvonne; Müller, Christina; Waarsing, Jan Hendrik; de Jong, Marion; Weinans, Harrie

    2015-12-05

    Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently reduce osteophytosis. Although widely applied in clinical care, the mechanism through which TA exerts this effect remains unknown. In this animal study, we investigated the in vivo effects of TA injections on macrophage activation, osteophyte development and joint degeneration. Furthermore, in vitro macrophage differentiation experiments were conducted to further explain working mechanisms of TA effects found in vivo. Osteoarthritis was induced in rat knees using papain injections and a running protocol. Untreated and TA-treated animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes. Synovial macrophage activation was measured in vivo using folate receptor β (FRβ)-targeted single-photon emission computed tomography/computed tomography. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology. To further explain the outcomes of our in vivo study, TA on macrophages was also studied in vitro. These cultured macrophages were either M1- or M2-activated, and they were analyzed using fluorescence-activated cell sorting for CD163 and FRβ expression as well as for messenger RNA (mRNA) expression of interleukin (IL)-10. Our in vivo study showed that intra-articular injections with TA strongly enhanced FRβ(+) macrophage activation. Despite stimulated macrophage activation, osteophyte formation was fully prevented. There was no beneficial effect of TA against cartilage degradation or subchondral bone sclerosis. In vitro macrophage cultures showed that TA strongly induced monocyte differentiation towards CD163(+) and FRβ(+) macrophages. Furthermore

  12. Preventing Occupational Skin Disease: A Review of Training Programs.

    PubMed

    Zack, Bethany; Arrandale, Victoria H; Holness, D Linn

    Occupational contact dermatitis (OCD) is a common occupational disease that impacts a variety of worker groups. Skin protection and disease prevention training programs have shown promise for improving prevention practices and reducing the incidence of OCD. This review details the features of training programs for primary prevention of OCD and identifies gaps in the literature. Twelve studies were identified for in-depth review: many studies included wet workers employed in health care, hairdressing, cleaning, and food preparation; 1 program featured manufacturing workers. Few programs provided content on allergic contact dermatitis, and only 1 was evaluated for long-term effectiveness. Effective programs were similar in content, delivery method, and timing and were characterized by industry specificity, multimodal learning, participatory elements, skin care resource provision, repeated sessions, and management engagement. Long-term effectiveness, generalizability beyond OCD, workplace health and safety culture impact, and translation of programs in the North American context represent areas for future research.

  13. Occupational Skin Disease Prevention: An Educational Intervention for Hairdresser Cosmetology Students.

    PubMed

    Haughtigan, Kara; Main, Eve; Bragg-Underwood, Tonya; Watkins, Cecilia

    2017-11-01

    Cosmetologists frequently develop occupational skin disease related to workplace exposures. The purpose of this study was to evaluate an educational intervention to increase cosmetology students' occupational skin disease knowledge and use of preventive practices. A quasi-experimental design was used to evaluate students' knowledge, behaviors, intentions, expectancies, and expectations. A 20-minute verbal presentation and printed two-page educational handout were provided for participants. Statistically significant increases in knowledge, frequency of glove use, and frequency of moisturizer use were found, but the frequency of handwashing did not increase. In addition, the Behavioral Strategies subscale, the Intention subscale, and the Expectancies subscale showed statistically significant improvements. The results of this study suggest an educational intervention can increase cosmetology students' knowledge of occupational skin diseases and their use of preventive strategies.

  14. Environmental and Occupational Interventions for Primary Prevention of Cancer: A Cross-Sectorial Policy Framework

    PubMed Central

    Espina, Carolina; Porta, Miquel; Schüz, Joachim; Aguado, Ildefonso Hernández; Percival, Robert V.; Dora, Carlos; Slevin, Terry; Guzman, Julietta Rodriguez; Meredith, Tim; Landrigan, Philip J.

    2013-01-01

    Background: Nearly 13 million new cancer cases and 7.6 million cancer deaths occur worldwide each year; 63% of cancer deaths occur in low- and middle-income countries. A substantial proportion of all cancers are attributable to carcinogenic exposures in the environment and the workplace. Objective: We aimed to develop an evidence-based global vision and strategy for the primary prevention of environmental and occupational cancer. Methods: We identified relevant studies through PubMed by using combinations of the search terms “environmental,” “occupational,” “exposure,” “cancer,” “primary prevention,” and “interventions.” To supplement the literature review, we convened an international conference titled “Environmental and Occupational Determinants of Cancer: Interventions for Primary Prevention” under the auspices of the World Health Organization, in Asturias, Spain, on 17–18 March 2011. Discussion: Many cancers of environmental and occupational origin could be prevented. Prevention is most effectively achieved through primary prevention policies that reduce or eliminate involuntary exposures to proven and probable carcinogens. Such strategies can be implemented in a straightforward and cost-effective way based on current knowledge, and they have the added benefit of synergistically reducing risks for other noncommunicable diseases by reducing exposures to shared risk factors. Conclusions: Opportunities exist to revitalize comprehensive global cancer control policies by incorporating primary interventions against environmental and occupational carcinogens. PMID:23384642

  15. UV-induced occupational skin cancer: possibilities of secondary individual prevention in the "Dermatologist's Procedure".

    PubMed

    Elsner, Peter; Blome, Otto; Diepgen, Thomas Ludwig

    2013-07-01

    Invasive squamous cell carcinoma (SCC) as a "quasi occupational disease" according to §9 Section 2 of the German Social Code Book (SGB) VII typically develops on chronically UV-damaged skin from actinic keratoses. After the Medical Scientific Committee of the Federal Ministry of Labor and Social Affairs has confirmed the legal criteria for acknowledging UV-induced SCC as an occupational disease, it is expected that the condition will be added to the official list of occupational diseases issued by the Federal Government in the near future. The Social Accident Insurance is required by law (§3 Occupational Disease Regulation) to prevent these tumors by "all appropriate means". There are excellent therapeutic and preventive measures for the management of actinic keratoses to avoid the development of SCC. The "Dermatologist's Procedure" according to §§ 41-43 of the agreement between the Social Accident Insurance and the Federal Medical Association was established in Germany in 1972 to take preventive measures in insured persons with skin lesions possibly developing into an occupational disease, or worsening it, or leading to a recurrence of it This procedure proved to be very successful in the prevention of severe and/or recurring skin diseases forcing a worker to leave his job. On the basis of this agreement, the Social Accident Insurance has the instruments to independently provide preventive measures for the new occupational skin disease SCC induced by natural UV light according to §9 Section 2 of the German Social Code Book (SGB) VII. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

  16. Effectiveness of interventions for preventing occupational irritant hand dermatitis: a quantitative systematic review.

    PubMed

    Papadatou, Zoi; Williams, Hector; Cooper, Kay

    2018-06-01

    The aim of this review was to identify, appraise and synthesize the best available evidence on the effectiveness of moisturizers, barrier creams, protective gloves, skin protection education and complex interventions (a combination of two or more of the interventions listed here) in preventing occupational irritant hand dermatitis (OIHD) in wet workers, comparing each intervention to an alternative intervention or to usual care (workers' regular skin care regimen). The most significant occupational skin problem potentially encountered in wet work occupations is occupational dermatitis. When the skin comes into contact with hazardous substances at work, this can cause occupational dermatitis. Substances which may cause occupational dermatitis include cleaning products, organic solvents, metalworking fluids, cement, flour, adhesives, other chemicals and even certain plants. Occupational skin disease has adverse effects on quality of life and the long term prognosis for skin health is poor unless workplace exposures are addressed. To date, no systematic review has been undertaken to determine the effectiveness of interventions for the primary prevention of OIHD in wet workers. The review included any workers from healthcare (e.g. nurses, doctors and allied health professionals) and also people in different wet work occupations (e.g. hairdressers, florists, catering workers, metal workers) at similar risk of OIHD. Studies that assessed the following interventions in the primary prevention of OIHD in wet workers at the workplace and at home (before and after work) were included:Types of studies considered were experimental study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, and before and after studies. Primary outcome measures were OIHD incidence, and secondary outcome measures were product evaluation and change of occupation because of OIHD versus staying in the occupation. Published and unpublished literature in

  17. 76 FR 28789 - Draft Alert Entitled “Preventing Occupational Respiratory Disease From Dampness in Office...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ... NIOSH-238] Draft Alert Entitled ``Preventing Occupational Respiratory Disease From Dampness in Office...), announces the availability of a draft Alert entitled ``Preventing Occupational Respiratory Disease from.../niosh/docket/review/docket238/default.html . The purpose of this Alert is to provide workers and...

  18. Occupational skin cancer induced by ultraviolet radiation and its prevention.

    PubMed

    Diepgen, T L; Fartasch, M; Drexler, H; Schmitt, J

    2012-08-01

    Skin cancer is by far the most common kind of cancer diagnosed in many western countries and ultraviolet radiation is the most important risk factor for cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Although employees at several workplaces are exposed to increased levels of UV radiation, skin cancer due to long-term intense occupational exposure to UV radiation is often not considered as occupational disease. The actually available evidence in the epidemiological literature clearly indicates that occupational UV radiation exposure is a substantial and robust risk factor for the development of cutaneous SCC and also clearly shows a significant risk for developing BCC. There is enough scientific evidence that outdoor workers have an increased risk of developing work-related occupational skin cancer due to natural UV radiation exposure and adequate prevention strategies must be implemented. The three measures which are successful and of particular importance in the prevention of nonmelanoma skin cancer in outdoor workers are changes in behaviour regarding awareness of health and disease resulting from exposure to natural UV radiation, protection from direct UV radiation by wearing suitable clothing, and regular and correct use of appropriate sunscreens. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  19. [Safety and health in work from the perspective of the Prevention of Occupational Hazards Act].

    PubMed

    Gómez-Hortigüela Amillo, J

    1996-01-01

    The passing of the Prevention of Occupational Hazards Act, (Ley 31/1995), constituted a change in direction in the development of occupational safety and health in Spain. This article describes the most salient points of this new legislation, from the criteria and principles that have to govern preventive activities, to the obligations and rights of both employers and workers, together with the co-operation and co-ordination of the activities of the various Administrations which have jurisdiction and the participation of employers' and workers' organisations, as the backbone of policy in matters concerning the prevention of occupational hazards.

  20. 76 FR 62093 - Preventing Occupational Hearing Loss: Stakeholder Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-06

    ..., including a discussion on personal protective equipment, hearing conservation programs and engineering... preventing occupational hearing loss and will include such subjects as the use of personal protective... protective equipment for noise control? What are the best practices for using feasible engineering controls...

  1. Trace elements in human alveolar macrophages studied by PIXE

    NASA Astrophysics Data System (ADS)

    Weber, G.; Roelandts, I.; Corhay, J. L.; Radermecker, M.; Delavignette, J. P.

    1990-04-01

    The purpose of this study is to determine the metal content of alveolar macrophages by PIXE from 94 subjects divided into two groups as follows: group (1) — subjects with non-occupational exposure to industrial dust: 30 healthy volunteers (controls), 16 patients suffering from lung cancer; group (2) — 48 healthy steel workers from the Liège area (blast-furnace [ n=29] and coke oven [ n=19]). We hope to define more precisely the influence of carcinoma, smoking habit, pathology and occupational exposure in the steel industry on the macrophage metal content. This study has shown: (a) an Fe and Sr increase and a Br decrease in the macrophages of smokers (especially in heavy smokers): (b) a significant Fe, Ti, Br and Cu increase and a trend to Pb, Cr, As and Sr increase in macrophages of healthy steel workers (especially blast-furnace workers) in comparison with non-exposed controls; (c) a significant Fe, Br, Cu and Zn increase and a trend to Pb, As and Ni increase in macrophages of non-exposed patients with lung cancer by comparison with non-exposed controls. The mechanism of metal change could be explained by professional exposure and endogenous changes (protein synthesis, inflammation, bronchial bleeding, …)

  2. Nudging for Prevention in Occupational Health and Safety in South Africa Using Fiscal Policies.

    PubMed

    de Jager, Pieter; Rees, David; Kisting, Sophia; Kgalamono, Spo; Ndaba, Mpume; Stacey, Nicolas; Tugendhaft, Aviva; Hofman, Karen

    2017-08-01

    Currently, in some countries occupational health and safety policy and practice have a bias toward secondary prevention and workers' compensation rather than primary prevention. Particularly, in emerging economies, research has not adequately contributed to effective interventions and improvements in workers' health. This article, using South Africa as a case study, describes a methodology for identifying candidate fiscal policy interventions and describes the policy interventions selected for occupational health and safety. It is argued that fiscal policies are well placed to deal with complex intersectoral health problems and to focus efforts on primary prevention. A major challenge is the lack of empirical evidence to support the effectiveness of fiscal policies in improving workers' health. A second challenge is the underprioritization of occupational health and safety partly due to the relatively small burden of disease attributed to occupational exposures. Both challenges can and should be overcome by (i) conducting policy-relevant research to fill the empirical gaps and (ii) reconceptualizing, both for policy and research purposes, the role of work as a determinant of population health. Fiscal policies to prevent exposure to hazards at work have face validity and are thus appealing, not as a replacement for other efforts to improve health, but as part of a comprehensive effort toward prevention.

  3. Evaluation of Occupational Therapy Workshops to Prevent Work-Related Injuries or Illnesses among Vocational Students

    ERIC Educational Resources Information Center

    Lecours, Alexandra; Therriault, Pierre-Yves

    2018-01-01

    The few studies aiming to evaluate prevention interventions provided by occupational therapists in health at work were conducted in work settings. However, to intervene in primary prevention, developing occupational therapy interventions with students learning a trade is relevant. The objective is to evaluate workshops designed and set up by…

  4. Unintentional injury prevention and the role of occupational therapy in the Solomon Islands: an integrative review.

    PubMed

    Daufanamae, Barbara U; Franklin, Richard C; Eagers, Jackie

    2016-01-01

    Unintentional injuries (injuries for which there is no evidence of a predetermined intent) are one of the leading causes of death worldwide, particularly in low- and middle-income countries (LMICs). Although evidence demonstrates unintentional injuries are preventable it is a public health challenge for many LMICs such as the Solomon Islands. Occupational therapists are well placed to contribute to injury prevention, as they have specialised skills to analyse the accessibility and safety of the environments within which people conduct their daily occupations. While the role of occupational therapy in unintentional injury prevention is well known in high-income countries, it is unfamiliar in LMICs, especially in the Solomon Islands. This integrative review aimed to explore the incidence of common unintentional injuries, and the burden in the Solomon Islands; and explore the potential role of occupational therapy in unintentional injury prevention in the Solomon Islands, based on current activities in LMICs. Articles were reviewed from six databases (Medline, CINAHL, OTDBase, OT Seeker, Scopus and PsychInfo). Five articles met the inclusion criteria for the first objective and 15 articles met the inclusion criteria for the second objective. These articles were thematically analysed where themes and codes associated with the research objectives were extracted and analysed. Unintentional injuries in the Solomon Islands reported in the literature included ocular trauma, falls from fruit trees and coconut palms, and road traffic crashes. Burden of injury reported was mostly associated with loss of productivity. Occupational therapists undertook rehabilitative, biomechanical, neurodevelopmental and educational roles in LMIC, focusing on tertiary and secondary injury prevention. This integrative review suggests that there is limited information regarding injury in the Solomon Islands. However, evidence is available in LMICs to suggest that occupational therapy services can

  5. The relationship between occupational sun exposure and non-melanoma skin cancer: clinical basics, epidemiology, occupational disease evaluation, and prevention.

    PubMed

    Fartasch, Manigé; Diepgen, Thomas Ludwig; Schmitt, Jochen; Drexler, Hans

    2012-10-01

    The cumulative effect of solar ultraviolet (UV) radiation is responsible for the worldwide increase in non-melanoma skin cancer, a category that includes squamous cell carcinoma and its precursors (the actinic keratoses) as well as basal-cell carcinoma. Non-melanoma skin cancer is the most common type of cancer in areas of the world with a light-skinned population. The occupational exposure to UV radiation is high in many outdoor occupations; recent studies suggest that persons working in such occupations are more likely to develop non-melanoma skin cancer. On the basis of a selective review of the literature, we present the current state of knowledge about occupational and non-occupational UV exposure and the findings of meta-analyses on the association of outdoor activity with non-melanoma skin cancer. We also give an overview of the current recommendations for prevention and for medicolegal assessment. Recent meta-analyses have consistently documented a significantly higher risk of squamous cell carcinoma of the skin among persons who work outdoors (odds ratio [OR] 1.77, 95% confidence interval [CI] 1.40-2.22, p<0.001). There is also evidence for an elevated risk of basal-cell carcinoma (OR 1.43, 95% CI 1.23-1.66, p = 0.0001), but the effect is of lesser magnitude and the study findings are not as uniform. The association of occupational exposure to solar UV radiation with squamous cell carcinoma, including actinic keratosis, has been conclusively demonstrated. It follows that, in Germany, suspected non-melanoma skin cancer in persons with high occupational exposure to UV radiation should be reported as an occupational disease under § 9, paragraph 2 of the Seventh Book of the German Social Code (Sozialgesetzbuch, SGB VII). Preventive measures are urgently needed for persons with high occupational exposure to UV radiation.

  6. [Prevention of occupational accidents with biological material as per Green and Kreuter Model].

    PubMed

    Manetti, Marcela Luisa; da Costa, João Carlos Souza; Marziale, Maria Helena Palucci; Trovó, Marli Elisa

    2006-03-01

    This study aimed at diagnosing the occurrence of occupational accidents deriving from exposition to biological substance among workers of a hospital from São Paulo, Brazil, analyzing the adopted safety measures and elaborating a flowchart of preventive actions according to the Health Promotion Model by Green and Kreuter. It is an exploratory study with data collected electronically from the website REPAT - Electronic Network for the Prevention of Occupational Accidents with biological substances. The strategy used by the hospital did not reduce the injures. Results were used to elaborate a flowchart of preventive actions in order to improve the workers' quality of life.

  7. 41 CFR 102-74.360 - What are the specific accident and fire prevention responsibilities of occupant agencies?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... accident and fire prevention responsibilities of occupant agencies? 102-74.360 Section 102-74.360 Public... MANAGEMENT REGULATION REAL PROPERTY 74-FACILITY MANAGEMENT Facility Management Accident and Fire Prevention § 102-74.360 What are the specific accident and fire prevention responsibilities of occupant agencies...

  8. The Fatality Assessment and Control Evaluation program's role in the prevention of occupational fatalities.

    PubMed

    Higgins, D N; Casini, V J; Bost, P; Johnson, W; Rautiainen, R

    2001-09-01

    The objective of the Fatality Assessment and Control Evaluation (FACE) program is to prevent traumatic occupational fatalities in the United States by identifying and investigating work situations at high risk for injury and formulating and disseminating prevention strategies to those who can intervene in the workplace. The FACE program is a research program located in the Division of Safety Research, a division of the National Institute for Occupational Safety and Health (NIOSH). NIOSH is an agency of the United States government and is part of the Centers for Disease Control and Prevention. NIOSH is responsible for conducting research and making recommendations for prevention of work related illnesses and injuries. FACE investigators conduct traumatic occupational fatality investigations throughout the United States and provide technical assistance to 15 state health or labor departments who have cooperative agreements with NIOSH to conduct traumatic fatality surveillance, targeted investigations, and prevention activities at the state level. Investigations are conducted at the worksite using the FACE model, an approach derived from the research conducted by William Haddon Jr. This approach reflects the public health perspective that the etiology of injuries is multifactorial and largely preventable. FACE investigators gather information on multiple factors that may have contributed to traumatic occupational fatalities. Information on factors associated with the agent (energy exchange, for example, thermal energy, mechanical energy, electrical energy, chemical energy), host (worker who died), and the environment (the physical and social aspects of the workplace), during the pre-event, event, and post-event time phases of the fatal incident are collected and analyzed. Organizational, behavioral, and environmental factors contributing to the death are detailed and prevention recommendations formulated and disseminated to help prevent future incidents of a similar

  9. Creating a Culture of Prevention in Occupational Safety and Health Practice.

    PubMed

    Kim, Yangho; Park, Jungsun; Park, Mijin

    2016-06-01

    The incidence of occupational injuries and diseases associated with industrialization has declined markedly following developments in science and technology, such as engineering controls, protective equipment, safer machinery and processes, and greater adherence to regulations and labor inspections. Although the introduction of health and safety management systems has further decreased the incidence of occupational injuries and diseases, these systems are not effective unless accompanied by a positive safety culture in the workplace. The characteristics of work in the 21(st) century have given rise to new issues related to workers' health, such as new types of work-related disorders, noncommunicable diseases, and inequality in the availability of occupational health services. Overcoming these new and emerging issues requires a culture of prevention at the national level. The present paper addresses: (1) how to change safety cultures in both theory and practice at the level of the workplace; and (2) the role of prevention culture at the national level.

  10. Climate change and occupational allergies: an overview on biological pollution, exposure and prevention.

    PubMed

    D'Ovidio, Maria Concetta; Annesi-Maesano, Isabella; D'Amato, Gennaro; Cecchi, Lorenzo

    2016-01-01

    Climate change, air pollution, temperature increase and other environmental variables are modifying air quality, contributing to the increase of prevalence of allergic respiratory diseases. Allergies are complex diseases characterized by multilevel interactions between individual susceptibility, response to immune modulation and environmental exposures to physical, chemical and biological agents. Occupational allergies introduce a further complexity to these relationships by adding occupational exposure to both the indoor and outdoor ones in the living environment. The aim of this paper is to overview climate-related allergy affecting environmental and occupational health, as literature data are scanty in this regard, and to suggest a management model of this risk based on a multidisciplinary approach, taking the case of biological pollution, with details on exposure and prevention. The management of climate-related occupational allergy should take into account preventive health strategies, environmental, public and occupational interventions, as well as to develop, implement, evaluate, and improve guidelines and standards protecting workers health under changing climatic conditions; new tools and strategies based on local conditions will have to be developed. Experimental studies and acquisition of environmental and personal data have to be matched to derive useful information for the scope of occupational health and safety.

  11. Prevention of injuries at work: the role of the occupational physician.

    PubMed

    Porru, Stefano; Placidi, Donatella; Carta, Angela; Alessio, Lorenzo

    2006-03-01

    To highlight the role of occupational physician (OP) in occupational injuries (OI) prevention and management. To suggest an approach beyond traditional focus on descriptive epidemiology, engineering interventions, administrative aspects of OI prevention. To promote a person- and enterprise-tailored approach, entailing greater attention to human factors and to practical problems of the specific workplace, with a call to a leading role played by OP. Analysis of the literature on the broader topic of OI prevention revealed thousands of publications; however, only a handful of them mention or describe the participation of OP in OI prevention. While recognizing that literature search is not the proper and only way to appreciate the current role of OP in this field, therefore, it seems necessary to call OP to a stronger effort in prevention and management of OI, through the context of a comprehensive intervention in cooperation with managers, supervisors, safety personnel and workers, focusing on specific needs of each enterprise. The following areas of OP intervention were examined: risk assessment, health surveillance, management, scientific research and health education. Within each of these topics, possible contributions, methodologies, instruments available for the OP were discussed, taking into account the relevant literature. Pathways for practical applications were illustrated, e.g., OI data generation and analyses, predictors of OI, fitness for work, case management, team work, educational issues, first aid, suggestion for OP contribution in specific research questions. OI continue to take a remarkable toll from individuals and society. New multidisciplinary interventions are needed to prevent OI. Focused activities at the single worksite with a central role from OP are definite options. OP is an effective interface between workforce and management and may offer, through a proactive approach, valuable practical and cultural contributions, while respecting

  12. [Causes and prevention of occupational cancer].

    PubMed

    Kawai, Kazuaki

    2013-10-01

    Cancer is the leading cause of death in Japan, and is responsible for 30 % of all deaths. Among these deaths, the contributing rate of occupational cancer is only a few percent. However, it is a serious problem for workers exposed to certain carcinogens within the workplace, because they are subjected to high levels of carcinogens throughout their workday. The early adverse health effects exerted by carcinogens are closely related to carcinogenesis. As biomarkers for cancer prevention, 8-hydroxydeoxyguanosine, as an oxidative stress marker, DNA adducts, and cytosine C-5 methylation, as a marker of epigenetic change, may be useful to monitor.

  13. Hazard Prevention Regarding Occupational Accidents Involving Blue-Collar Foreign Workers: A Perspective of Taiwanese Manpower Agencies

    PubMed Central

    Chang, Huan-Cheng; Wang, Mei-Chin; Liao, Hung-Chang; Cheng, Shu-Fang; Wang, Ya-huei

    2016-01-01

    Since 1989, blue-collar foreign workers have been permitted to work in Taiwanese industries. Most blue-collar foreign workers apply for jobs in Taiwan through blue-collar foreign workers’ agencies. Because blue-collar foreign workers are not familiar with the language and culture in Taiwan, in occupational accident education and hazard prevention, the agencies play an important role in the coordination and translation between employees and blue-collar foreign workers. The purpose of this study is to establish the agencies’ role in the occupational accidents education and hazard prevention for blue-collar foreign workers in Taiwan. This study uses a qualitative method—grounded theory—to collect, code, and analyze the data in order to understand the agencies’ role in occupational accident education and hazard prevention for blue-collar foreign workers in Taiwan. The results show that the duty of agencies in occupational accident education and hazard prevention includes selecting appropriate blue-collar foreign workers, communicating between employees and blue-collar foreign workers, collecting occupational safety and health information, assisting in the training of occupational safety and health, and helping blue-collar foreign workers adapt to their lives in Taiwan. Finally, this study suggests seven important points and discusses the implementation process necessary to improve governmental policies. The government and employees should pay attention to the education/training of occupational safety and health for blue-collar foreign workers to eliminate unsafe behavior in order to protect the lives of blue-collar foreign workers. PMID:27420085

  14. Hazard Prevention Regarding Occupational Accidents Involving Blue-Collar Foreign Workers: A Perspective of Taiwanese Manpower Agencies.

    PubMed

    Chang, Huan-Cheng; Wang, Mei-Chin; Liao, Hung-Chang; Cheng, Shu-Fang; Wang, Ya-Huei

    2016-07-13

    Since 1989, blue-collar foreign workers have been permitted to work in Taiwanese industries. Most blue-collar foreign workers apply for jobs in Taiwan through blue-collar foreign workers' agencies. Because blue-collar foreign workers are not familiar with the language and culture in Taiwan, in occupational accident education and hazard prevention, the agencies play an important role in the coordination and translation between employees and blue-collar foreign workers. The purpose of this study is to establish the agencies' role in the occupational accidents education and hazard prevention for blue-collar foreign workers in Taiwan. This study uses a qualitative method-grounded theory-to collect, code, and analyze the data in order to understand the agencies' role in occupational accident education and hazard prevention for blue-collar foreign workers in Taiwan. The results show that the duty of agencies in occupational accident education and hazard prevention includes selecting appropriate blue-collar foreign workers, communicating between employees and blue-collar foreign workers, collecting occupational safety and health information, assisting in the training of occupational safety and health, and helping blue-collar foreign workers adapt to their lives in Taiwan. Finally, this study suggests seven important points and discusses the implementation process necessary to improve governmental policies. The government and employees should pay attention to the education/training of occupational safety and health for blue-collar foreign workers to eliminate unsafe behavior in order to protect the lives of blue-collar foreign workers.

  15. Do workers' health surveillance examinations fulfill their occupational preventive objective? Analysis of the medical practice of occupational physicians in Catalonia, Spain.

    PubMed

    Rodríguez-Jareño, Mari Cruz; Molinero, Emilia; de Montserrat, Jaume; Vallès, Antoni; Aymerich, Marta

    2017-10-06

    Although routine workers' health examinations are extensively performed worldwide with important resource allocation, few studies have analyzed their quality. The objective of this study has been to analyze the medical practice of workers' health examinations in Catalonia (Spain) in terms of its occupational preventive aim. A cross-sectional study was carried out by means of an online survey addressed to occupational physicians who were members of the Catalan Society of Safety and Occupational Medicine. The questionnaire included factual questions on how they performed health examinations in their usual practice. The bivariate analysis of the answers was performed by type of occupational health service (external/internal). The response rate was 57.9% (N = 168), representing 40.3% of the reference population. A high percentage of occupational physicians had important limitations in their current medical practice, including availability of clinical and exposure information, job-specificity of tests, and early detection and appropriate management of suspected occupational diseases. The situation in external occupational health services - that covered the great majority of Catalan employees - was worse remarkably in regard to knowledge of occupational and nonoccupational sickness absence data, participation in the investigation of occupational injuries and diseases, and accessibility for workers to the occupational health service. This study raises serious concerns about the occupational preventive usefulness of these health examinations, and subsequently about our health surveillance system, based primarily on them. Professionals alongside health and safety institutions and stakeholders should promote the rationalization of this system, following the technical criteria of need, relevance, scientific validity and effectiveness, whilst ensuring that its ultimate goal of improving the health and safety of workers in relation to work is fulfilled. Other countries with

  16. The role of worker education in preventing occupational lung disease.

    PubMed

    Kaufman, J D; Rosenstock, L

    1991-01-01

    Training and education of workers in order to prevent occupational lung diseases represent a challenge to employers, unions, clinicians, and other interested groups. Programs attempting to meet this need range from simple programs in respiratory protection fundamentals and smoking cessation to programs that teach workers to understand and demand their right to a safe and healthful workplace. Support for educational programs has come from diverse sources, including government, labor, business, and independent organizations. In some cases nonprofit organizations have developed innovative programs, but it is important that the burden of preventing occupational lung disease through education not be carried by charitable organizations alone. The role of the clinician in this effort is to educate workers at every opportunity regarding lung hazards and to use early evidence of respiratory damage as a lever to increase the worker's understanding of his or her role in health protection.

  17. Dipeptidyl Peptidase-4 Inhibitor Anagliptin Prevents Intracranial Aneurysm Growth by Suppressing Macrophage Infiltration and Activation.

    PubMed

    Ikedo, Taichi; Minami, Manabu; Kataoka, Hiroharu; Hayashi, Kosuke; Nagata, Manabu; Fujikawa, Risako; Higuchi, Sei; Yasui, Mika; Aoki, Tomohiro; Fukuda, Miyuki; Yokode, Masayuki; Miyamoto, Susumu

    2017-06-19

    Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP-4 (dipeptidyl peptidase-4) inhibitors have anti-inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP-4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. IAs were surgically induced in 7-week-old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin. We measured the morphologic parameters of aneurysms over time and their local inflammatory responses. To investigate the molecular mechanisms, we used lipopolysaccharide-treated RAW264.7 macrophages. In the anagliptin-treated group, aneurysms were significantly smaller 2 to 4 weeks after IA induction. Anagliptin inhibited the accumulation of macrophages in IAs, reduced the expression of MCP-1 (monocyte chemotactic protein 1), and suppressed the phosphorylation of p65. In lipopolysaccharide-stimulated RAW264.7 cells, anagliptin treatment significantly reduced the production of tumor necrosis factor α, MCP-1, and IL-6 (interleukin 6) independent of GLP-1 (glucagon-like peptide 1), the key mediator in the antidiabetic effects of DPP-4 inhibitors. Notably, anagliptin activated ERK5 (extracellular signal-regulated kinase 5), which mediates the anti-inflammatory effects of statins, in RAW264.7 macrophages. Preadministration with an ERK5 inhibitor blocked the inhibitory effect of anagliptin on MCP-1 and IL-6 expression. Accordingly, the ERK5 inhibitor also counteracted the suppression of p65 phosphorylation in vitro. A DPP-4 inhibitor, anagliptin, prevents the growth of IAs via its anti-inflammatory effects on macrophages. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  18. CYP epoxygenase 2J2 prevents cardiac fibrosis by suppression of transmission of pro-inflammation from cardiomyocytes to macrophages

    PubMed Central

    Yang, Lei; Ni, Li; Duan, Quanlu; Wang, Xingxu; Chen, Chen; Chen, Song; Chaugai, Sandip; Zeldin, D.C.; Tang, Jia Rong; Wang, Dao Wen

    2017-01-01

    Cytochrome P450 epoxygenase (CYP450)-derived epoxyeicosatrienoic acids (EETs) are important regulators of cardiac remodeling; but the underlying mechanism remains unclear. The present study aimed to elucidate how EETs regulated cardiac fibrosis in response to isoprenaline (Iso) or angiotensin (Ang) II. Cardiac-specific human CYP2J2 transgenic mice (Tr) and wild-type (WT) C57BL/6 littermates were infused with Iso- or Ang II. Two weeks after infusion, Tr mice showed more alleviative cardiac fibrosis and inflammation compared with WT mice. In vitro, we found Iso or Ang II induced nuclear transfer of NF-κB p65 and inflammatory cytokines expression in cardiomyocytes. Furthermore, inflammation response emerged in macrophages cultured in cardiomyocytes-conditioned medium. When pretreatment with 14,15-EET in cardiomyocytes, the inflammatory response was markedly suppressed and the transmission of inflammation from cardiomyocytes to macrophages was reduced. In conclusion, CYP2J2 and EETs prevent cardiac fibrosis and cardiac dysfunction by suppressing transmission of pro-inflammation from cardiomyocytes to macrophages in heart, suggesting that elevation of EETs level could be a potential strategy to prevent cardiac fibrosis. PMID:25686540

  19. Systematic Review of Interventions Supported by ICT for the Prevention Treatment of Occupational Stress.

    PubMed

    Narváez, Santiago; Tobar, Angela M; López, Diego M

    2014-01-01

    Stress-related disorders have become one of the main problems of public health in many countries and of worldwide organizations, and they are expected to become more common in the forthcoming decades. This article aims at providing a systematic review and a descriptive evaluation of the interventions supported by ICT for the prevention and treatment of occupational stress. A systematic review of five databases (EBSCO, The Cochrane Library, PubMed, ScienceDirect and IEEEXplorer) was carried out. This article provides a quantitative and qualitative description of 21 studies about occupational stress interventions supported by ICT. The following factors were considered for the analysis: impact of the intervention, design of the study, type of intervention, purpose of the intervention, type of instrument for the measurement of occupational stress, and type of ICT used. The systematic review demonstrated that interventions supported by ICT for the prevention and treatment of occupational stress are scarce but effective.

  20. The potential impact of epidemiology on the prevention of occupational disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wegman, D.H.

    1992-07-01

    This presentation reviews occupational epidemiology as a foundation for workplace disease prevention activities. By examining descriptive, etiologic and intervention occupational epidemiology studies, a range of opportunities are illustrated where epidemiology has played, or could play a principal role in guiding preventive efforts. Descriptive studies presented include ones based on vital records, on epidemic investigations, cross-sectional surveys, and surveillance. Etiologic studies review the largely successful development of knowledge for lung cancer and asbestos exposure for pulmonary effects of isocyanate exposures. However, attention is also directed to the need for etiologic studies of work environment risks for both cardiovascular and musculoskeletal disease.more » Finally importance is placed on the too infrequent epidemiologic studies of intervention. Historical examples of control of large risks from nickel cancers and silicosis are balanced with more recent examples of successes at reducing smaller risks of cardiovascular disease and oil acne. Throughout, emphasis is placed on the importance of reintegrating the academic discipline of epidemiology into the application of study findings to prevention of workplace risks.67 references.« less

  1. Resveratrol Prevents Tumor Growth and Metastasis by Inhibiting Lymphangiogenesis and M2 Macrophage Activation and Differentiation in Tumor-associated Macrophages.

    PubMed

    Kimura, Yoshiyuki; Sumiyoshi, Maho

    2016-01-01

    Antitumor and antimetastatic effects of resveratrol on tumor-induced lymphangiogenesis through the regulation of M2 macrophages in tumor-associated macrophages currently remain unknown. Therefore, we herein examined the effects of resveratrol on M2 macrophage activation and differentiation, and those of resveratrol-treated condition medium (CM) in M2 macrophages on vascular endothelial cell growth factor (VEGF)-C-induced migration, invasion, and tube formation by human lymphatic endothelial cells (HLECs). Resveratrol (50 μM or 5-50 μM) inhibited the production of interleukin-10 and monocyte chemoattractant protein-1 in M2 macrophages, whereas it promoted that of transforming growth factor-β1. Resveratrol (25 and 50 μM) inhibited the phosphorylation of signal transducer and activator of transcript 3 without affecting its expression in the differentiation process of M2 macrophages. Furthermore, resveratrol-treated CM of M2 macrophages inhibited VEGF-C-induced HLEC migration, invasion, and lymphangiogenesis. Resveratrol (25 mg/kg, twice daily) inhibited tumor growth and metastasis to the lung and also reduced the area of lymphatic endothelial cells in tumors (in vivo). These results suggest that the antitumor and antimetastatic effects of resveratrol were partly due to antilymphangiogenesis through the regulation of M2 macrophage activation and differentiation.

  2. The Union Health Center: a working model of clinical care linked to preventive occupational health services.

    PubMed

    Herbert, R; Plattus, B; Kellogg, L; Luo, J; Marcus, M; Mascolo, A; Landrigan, P J

    1997-03-01

    As health care provision in the United States shifts to primary care settings, it is vital that new models of occupational health services be developed that link clinical care to prevention. The model program described in this paper was developed at the Union Health Center (UHC), a comprehensive health care center supported by the International Ladies Garment Workers Union (now the Union of Needletrades, Industrial and Textile Employees) serving a population of approximately 50,000 primarily minority, female garment workers in New York City. The objective of this paper is to describe a model occupational medicine program in a union-based comprehensive health center linking accessible clinical care with primary and secondary disease prevention efforts. To assess the presence of symptoms suggestive of occupational disease, a health status questionnaire was administered to female workers attending the UHC for routine health maintenance. Based on the results of this survey, an occupational medicine clinic was developed that integrated direct clinical care with worker and employer education and workplace hazard abatement. To assess the success of this new approach, selected cases of sentinel health events were tracked and a chart review was conducted after 3 years of clinic operation. Prior to initiation of the occupational medicine clinic, 64% (648) of the workers surveyed reported symptoms indicative of occupational illnesses. However, only 42 (4%) reported having been told by a physician that they had an occupational illness and only 4 (.4%) reported having field a workers' compensation claim for an occupational disease. In the occupational medicine clinic established at the UHC, a health and safety specialist acts as a case manager, coordinating worker and employer education as well as workplace hazard abatement focused on disease prevention, ensuring that every case of occupational disease is treated as a potential sentinel health event. As examples of the success

  3. Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages.

    PubMed

    Hernández-Ledesma, Blanca; Hsieh, Chia-Chien; de Lumen, Ben O

    2009-12-18

    Oxidative stress and inflammation are two of the most critical factors implicated in carcinogenesis and other degenerative disorders. We have investigated how lunasin, a known anti-cancer seed peptide, affect these factors. This peptide inhibits linoleic acid oxidation and acts as 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenger. Furthermore, using LPS-stimulated RAW 264.7 macrophages, we have demonstrated that lunasin reduces, in a significant dose-dependent manner, the production of reactive oxygen species (ROS) by LPS-induced macrophages. Lunasin also inhibits the release of pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukine-6 [IL-6]). On the basis of these potent antioxidant and anti-inflammatory properties, we propose lunasin not only as a cancer preventive and therapeutic agent but also as an agent against other inflammatory-related disorders.

  4. [Preventing addictive practices in the workplace thanks to occupational health services].

    PubMed

    Dano, Corinne

    2017-06-01

    The workplace can be concerned by all types and all levels of addictive practices: consumption of alcohol or psychoactive substances, work addiction, internet addiction and technology addiction. Addictions can be related to multiple factors, both within and outside the workplace. With the employer, responsible for occupational health and safety, the multidisciplinary team of the inter-company occupational health service must today implement a collective and global prevention policy with regard to addictions, in addition to the traditional follow-up. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. [Occupational physician's role in the prevention of the accidents in construction industry].

    PubMed

    Mosconi, G; Riva, M M; Apostoli, P

    2008-01-01

    The aim of this work is to discuss about the role of the occupational physician in the prevention of the accidents in construction industry. Using the experience of 12 years of surveillance of workers in Bergamo province, the authors analyse the "human factors" which may influence the risk to have an accident, and the role of the physicians not only for the early diagnosis of work-related diseases, but also for the formulation of correct fitness to work, which consider accidents' prevention. Health conditions, psychological elements, fatigue and life style are some of the most important "human factors" which can amplify the accident phenomenon in construction industry. Our experience demonstrates that the occupational physicians can operate in preventive way on these factors, formulating correct fitness to work, giving their collaboration in the risk evaluation and management, suggesting runs of rehabilitation and recovery for the workers who need it, promoting information meetings related to the correct life habits.

  6. Economic evaluation of occupational safety preventive measures in a hospital.

    PubMed

    Ramos, Delfina G; Arezes, Pedro M; Afonso, Paulo

    2015-01-01

    When an organization performs an integrated analysis of risks through its Occupational Health and Safety Management System, several steps are suggested to address the implications of the identified risks. Namely, the organization should make a detailed analysis of the monetary impact for the organization of each of the preventive measures considered. However, it is also important to perform an analysis of the impact of each measure on society (externalities). The aim of this paper is to present a case study related to the application of the proposed economic evaluation methodology. An analysis of the work accidents in a hospital has been made. Three of the major types of accidents have been selected: needle stings, falls and excessive strain. Following the risk assessment, some preventive measures have been designed. Subsequently, the Benefit/Cost ratio (B/C) of these measures has been calculated, both in financial terms (from the organization's perspective) and in economic terms (including the benefits for the worker and for the Society). While the financial ratio is only advantageous in some cases, when the externalities are taken into account, the B/C ratio increases significantly. It is important to consider external benefits to make decisions concerning the implementation of preventive measures in Occupational Health and Safety projects.

  7. Apoptosis inhibitor of macrophage (AIM) is required for obesity-associated recruitment of inflammatory macrophages into adipose tissue

    PubMed Central

    Kurokawa, Jun; Nagano, Hiromichi; Ohara, Osamu; Kubota, Naoto; Kadowaki, Takashi; Arai, Satoko; Miyazaki, Toru

    2011-01-01

    Infiltration of inflammatory macrophages into adipose tissues with the progression of obesity triggers insulin resistance and obesity-related metabolic diseases. We recently reported that macrophage-derived apoptosis inhibitor of macrophage (AIM) protein is increased in blood in line with obesity progression and is incorporated into adipocytes, thereby inducing lipolysis in adipose tissue. Here we show that such a response is required for the recruitment of adipose tissue macrophages. In vitro, AIM-dependent lipolysis induced an efflux of palmitic and stearic acids from 3T3-L1 adipocytes, thereby stimulating chemokine production in adipocytes via activation of toll-like receptor 4 (TLR4). In vivo administration of recombinant AIM to TLR4-deficient (TLR4−/−) mice resulted in induction of lipolysis without chemokine production in adipose tissues. Consistently, mRNA levels for the chemokines that affect macrophages were far lower in AIM-deficient (AIM−/−) than in wild-type (AIM+/+) obese adipose tissue. This reduction in chemokine production resulted in a marked prevention of inflammatory macrophage infiltration into adipose tissue in obese AIM−/− mice, although these mice showed more advanced obesity than AIM+/+ mice on a high-fat diet. Diminished macrophage infiltration resulted in decreased inflammation locally and systemically in obese AIM−/− mice, thereby protecting them from insulin resistance and glucose intolerance. These results indicate that the increase in blood AIM is a critical event for the initiation of macrophage recruitment into adipose tissue, which is followed by insulin resistance. Thus, AIM suppression might be therapeutically applicable for the prevention of obesity-related metabolic disorders. PMID:21730133

  8. Proactive prevention in occupational safety and health: how to identify tomorrow's prevention priorities and preventive measures.

    PubMed

    Hauke, Angelika; Flaspöler, Eva; Reinert, Dietmar

    2018-04-17

    Global trends such as digitalisation, globalisation and demographic change are changing workplaces, and accordingly occupational safety and health (OSH) needs. To better prepare for the future and to foster proactive prevention, the German Social Accident Insurance (DGUV) established an OSH risk observatory (RO OSH). The RO OSH relies on an online survey and calls upon the expertise of labour inspectors. 398 labour inspectors participated in the first RO OSH enquiry. They rated developments with regard to their sector-specific relevance for OSH in the near future. The RO OSH also provides ideas for preventive measures that can be implemented by the German Social Accident Insurance Institutions. Work intensity, demographic aspects, and digitalisation play a major role for most or all sectors. However, familiar OSH issues such as musculoskeletal strain and noise also continue to be of major importance and require further consideration and specific solutions in prevention. For the DGUV, training and consulting bear great potential for proactive prevention in the above priority areas, e.g. by fostering a prevention culture and supporting companies in (psychosocial) risk assessment (also for mobile work). For instance, concepts for increasing physical activity at sedentary workplaces, and data security require continued research.

  9. Glutamine Modulates Macrophage Lipotoxicity

    PubMed Central

    He, Li; Weber, Kassandra J.; Schilling, Joel D.

    2016-01-01

    Obesity and diabetes are associated with excessive inflammation and impaired wound healing. Increasing evidence suggests that macrophage dysfunction is responsible for these inflammatory defects. In the setting of excess nutrients, particularly dietary saturated fatty acids (SFAs), activated macrophages develop lysosome dysfunction, which triggers activation of the NLRP3 inflammasome and cell death. The molecular pathways that connect lipid stress to lysosome pathology are not well understood, but may represent a viable target for therapy. Glutamine uptake is increased in activated macrophages leading us to hypothesize that in the context of excess lipids glutamine metabolism could overwhelm the mitochondria and promote the accumulation of toxic metabolites. To investigate this question we assessed macrophage lipotoxicity in the absence of glutamine using LPS-activated peritoneal macrophages exposed to the SFA palmitate. We found that glutamine deficiency reduced lipid induced lysosome dysfunction, inflammasome activation, and cell death. Under glutamine deficient conditions mTOR activation was decreased and autophagy was enhanced; however, autophagy was dispensable for the rescue phenotype. Rather, glutamine deficiency prevented the suppressive effect of the SFA palmitate on mitochondrial respiration and this phenotype was associated with protection from macrophage cell death. Together, these findings reveal that crosstalk between activation-induced metabolic reprogramming and the nutrient microenvironment can dramatically alter macrophage responses to inflammatory stimuli. PMID:27077881

  10. Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.

    2006-02-15

    Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs.more » On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-{alpha} levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later.« less

  11. [Prevention of Occupational Injuries Related to Hands: Calculation of Subsequent Injury Costs for the Austrian Social Occupational Insurance Institution (AUVA)].

    PubMed

    Rauner, M S; Mayer, B; Schaffhauser-Linzatti, M M

    2015-08-01

    Occupational injuries cause short-term, direct costs as well as long-term follow-up costs over the lifetime of the casualties. Due to shrinking budgets accident insurance companies focus on cost reduction programmes and prevention measures. For this reason, a decision support system for consequential cost calculation of occupational injuries was developed for the main Austrian social occupational insurance institution (AUVA) during three projects. This so-called cost calculation tool combines the traditional instruments of accounting with quantitative methods such as micro-simulation. The cost data are derived from AUVA-internal as well as external economic data sources. Based on direct and indirect costs, the subsequent occupational accident costs from the time of an accident and, if applicable, beyond the death of the individual casualty are predicted for the AUVA, the companies in which the casualties are working, and the other economic sectors. By using this cost calculation tool, the AUVA classifies risk groups and derives related prevention campaigns. In the past, the AUVA concentrated on falling, accidents at construction sites and in agriculture/forestry, as well as commuting accidents. Currently, among others, a focus on hand injuries is given and first prevention programmes have been initiated. Hand injuries represent about 38% of all casualties with average costs of about 7,851 Euro/case. Main causes of these accidents are cutting injuries in production, agriculture, and forestry. Beside a low, but costly, number of amputations with average costs of more than 100,000 Euro/case, bone fractures and strains burden the AUVA-budget with about 17,500 and 10,500 € per case, respectively. Decision support systems such as this cost calculation tool represent necessary instruments to identify risk groups and their injured body parts, causes of accidents, and economic activities, which highly burden the budget of an injury company, and help derive

  12. Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype.

    PubMed

    Campbell, Gillian M; Nicol, Marlynne Q; Dransfield, Ian; Shaw, Darren J; Nash, Anthony A; Dutia, Bernadette M

    2015-10-01

    The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection.

  13. [Field investigation of occupational disease diagnosis in Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014: an analysis of 136 cases].

    PubMed

    Fan, C Y; Li, X D; Wen, W; Wang, Y Y; Zhang, Y; Lang, L

    2016-04-20

    To investigate the characteristics of 136 patients with occupational diseases, to summarize key techniques used in field investigation, and to provide a scientific basis for the development of standard operating procedures for field investigation of occupational disease diagnosis. Field investigation and routine data analysis were performed to analyze the cases diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from January 2009 to December 2014. A total of 136 cases of occupational diseases were diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014, and there were 66 cases of leukemia, 18 cases of suspected occupational benzene poisoning, 12 cases of suspected occupational handarm vibration disease, and 11 cases of suspected pneumoconiosis. Of all these patients, 41.91% were engaged in at least three types of work, 70.59% were exposed to at least three types of chemicals, 25.74% experienced changes in technical processes and chemicals, and 47.06% had disputes on the chemicals they were exposed to during verification by both parties. Occupational hazard factors were detected. Most samples (358)were used to measure benzene concentration in workplace air, among which 11.7% had a benzene concentration of >6.00 mg/m(3)(exceeding standard), 13.41% had a benzene concentration of 3.26~6.00 mg/m(3), 75.42% had a benzene concentration of<0.03 to <3.25 mg/m(3). The samples of suspected occupational hand-arm vibration disease, suspected pneumoconiosis, and suspected occupational noiseinduced hearing loss had high overstandard rates (100%, 93.8%, and 83.3%, respectively). Field investigation of occupational disease diagnosis reveals large numbers of cases of leukemia, suspected occupational benzene poisoning, suspected occupational hand-arm vibration disease, and suspected pneumoconiosis. The key aspects of field investigation include confirmation of the history of occupational

  14. Dropout Prevention: Diversified Satellite Occupations Program and Career Development. Final Report.

    ERIC Educational Resources Information Center

    Jones, Hilda B.

    The Diversified Satellite Occupations Program Career Development sought to prevent dropout through these strategies: registration at a school situation away from the normal school setting, creation of a close teacher-student relationship, and raise achievement levels and lower anxiety levels. Program emphases at elementary, junior and senior high…

  15. Neuropeptide Y stimulation as primary target for preventive measures of maladaptative cardiovascular reactions in occupational chronic stress exposure.

    PubMed

    Ciumaşu-Rîmbu, Mălina; Popa, Livia; Vulpoi, Carmen

    2012-01-01

    Chronic stress may produce a decrease in central NPY expression and subjects exposed to it may prove hypersensitivity to a novel stressor with dysfunctions in the NPY system and cardiovascular maladaptation to stress, even hypertension. Upregulation of NPY expression may contribute to successful behavioral adaptation to stress by reducing cardiovascular tone and suppressing anxious behaviors. Adaptogens, a new class of metabolic regulators stimulate NPY expression and release. The aim of this study is to increase tolerance and adaptation to stress of hypersensitive to novel stressor, occupational chronic stress exposed subjects with cardiovascular maladaptation to mild new stressor using adaptogens as part of prevention protocol. 40 military personnel with known cardiostressor reactional mode and occupational chronic stress exposure were exposed to mild novel stressor: occupational medicine routine evaluation and clinically assessed for maladaptative cardiovascular response prior and before application of 30 day prevention protocol. Employees were randomly split in two groups, one receiving standard prevention protocol (lifestyle counseling) plus adaptogens in multiple dose administration, twice daily and the other receiving only standard prevention protocol. We found significant statistic differences in all cardiovascular parameters in adaptogen group and only in diastolic blood pressure in control group. Adaptogens could be an important factor in successful prevention protocols of chronic occupational stress dysfunctions involving NPY systems.

  16. 76 FR 30366 - Draft Alert Entitled “Preventing Occupational Respiratory Disease From Dampness in Office...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [Docket Number NIOSH-238] Draft Alert Entitled ``Preventing Occupational Respiratory Disease From Dampness in Office Buildings, Schools, and Other Nonindustrial Buildings;'' Correction A notice of draft document for public...

  17. Conditional deletion of caspase-8 in macrophages alters macrophage activation in a RIPK-dependent manner.

    PubMed

    Cuda, Carla M; Misharin, Alexander V; Khare, Sonal; Saber, Rana; Tsai, FuNien; Archer, Amy M; Homan, Philip J; Haines, G Kenneth; Hutcheson, Jack; Dorfleutner, Andrea; Budinger, G R Scott; Stehlik, Christian; Perlman, Harris

    2015-10-16

    Although caspase-8 is a well-established initiator of apoptosis and suppressor of necroptosis, recent evidence suggests that this enzyme maintains functions beyond its role in cell death. As cells of the innate immune system, and in particular macrophages, are now at the forefront of autoimmune disease pathogenesis, we examined the potential involvement of caspase-8 within this population. Cre (LysM) Casp8 (fl/fl) mice were bred via a cross between Casp8 (fl/fl) mice and Cre (LysM) mice, and RIPK3 (-/-) Cre (LysM) Casp8 (fl/fl) mice were generated to assess the contribution of receptor-interacting serine-threonine kinase (RIPK)3. Immunohistochemical and immunofluorescence analyses were used to examine renal damage. Flow cytometric analysis was employed to characterize splenocyte distribution and activation. Cre (LysM) Casp8 (fl/fl) mice were treated with either Toll-like receptor (TLR) agonists or oral antibiotics to assess their response to TLR activation or TLR agonist removal. Luminex-based assays and enzyme-linked immunosorbent assays were used to measure cytokine/chemokine and immunoglobulin levels in serum and cytokine levels in cell culture studies. In vitro cell culture was used to assess macrophage response to cell death stimuli, TLR activation, and M1/M2 polarization. Data were compared using the Mann-Whitney U test. Loss of caspase-8 expression in macrophages promotes onset of a mild systemic inflammatory disease, which is preventable by the deletion of RIPK3. In vitro cell culture studies reveal that caspase-8-deficient macrophages are prone to a caspase-independent death in response to death receptor ligation; yet, caspase-8-deficient macrophages are not predisposed to unchecked survival, as analysis of mixed bone marrow chimeric mice demonstrates that caspase-8 deficiency does not confer preferential expansion of myeloid populations. Loss of caspase-8 in macrophages dictates the response to TLR activation, as injection of TLR ligands upregulates

  18. Occupational contact urticaria: lessons from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P).

    PubMed

    Bensefa-Colas, L; Telle-Lamberton, M; Faye, S; Bourrain, J-L; Crépy, M-N; Lasfargues, G; Choudat, D; Momas, I

    2015-12-01

    Occupational contact urticaria (OCU) is an occupational contact dermatitis that can cause serious health consequences and disability at work. To describe OCU and its temporal trends by the main causal agents and activity sectors in a nationwide scheme in France. Using data from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P), we described OCU reported during the period 2001-10 and analysed the temporal trends of OCU and OCU attributed to the most frequent agents over the study period. Trends analyses were supported by reporting odds ratios using a logistic regression model with reference to 2001, or with time as a continuous variable. During the study period, 251 cases of OCU were reported in RNV3P, half of which were due to natural rubber latex, in particular in the health and social work activity sector (HSW). The number of these cases declined significantly over the study period (19% per year), and particularly after 2006. Conversely, the other causes of OCU did not decrease. Using surveillance data from a French national network, this study has found that there was a significant decline in OCU due to natural rubber latex, particularly in the HSW, when powdered latex gloves were banned from French hospitals. Our results show the effectiveness of this preventive measure, and suggest that this practice should be extended to other sectors. © 2015 British Association of Dermatologists.

  19. [Prevention of occupational solar UV radiation-induced epithelial skin cancer].

    PubMed

    Bauer, A; Beissert, S; Knuschke, P

    2015-03-01

    Malignancies of the skin, with an incidence of more than 200,000 newly registered cases/year, are the most frequently notified malignances in Germany. In Europe, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) account for about 30 cases/100,000 persons and 50-100 cases/100,000 persons, respectively. Ultraviolet (UV) exposure is the main risk factor to induce these cancers. Increased incidence rates were shown for persons having red/blonde hair as well as light eye colour, acquire sun burns easily, hardly tan and develop freckles. The majority of the malignancies and precursor lesions are acquired by UV exposure in leisure time. However, in highly occupationally UV-exposed outdoor workers, UV monitoring revealed that exposure levels are 2-3 times higher compared to the general population. Occupations likely to be highly exposed are farmers, forestry workers, gardeners, landscapers, fishermen and seafarers, construction workers, builders, tin smiths, sport teachers, mountain guides, etc. Recent metaanalyses showed that occupational UV exposure is a relevant and independent risk factor for SCC and to a lesser extent also for BCC. To prevent occupationally caused malignancies of the skin a significant reduction of occupationally acquired UV dosages in outdoor workers is mandatory. Relevant factors influencing the cumulative sun exposure in outdoor workers are the amount of UV exposure, the specific tasks to be performed in the sun as well as the UV protection habits of the workers. Besides adequate behavior, textile protection by headgear and clothing as well as the regular use of sunscreens and sun glasses are important.

  20. Paternal occupation and birth defects: findings from the National Birth Defects Prevention Study.

    PubMed

    Desrosiers, Tania A; Herring, Amy H; Shapira, Stuart K; Hooiveld, Mariëtte; Luben, Tom J; Herdt-Losavio, Michele L; Lin, Shao; Olshan, Andrew F

    2012-08-01

    Several epidemiological studies have suggested that certain paternal occupations may be associated with an increased prevalence of birth defects in offspring. Using data from the National Birth Defects Prevention Study, the authors investigated the association between paternal occupation and birth defects in a case-control study of cases comprising over 60 different types of birth defects (n=9998) and non-malformed controls (n=4066) with dates of delivery between 1997 and 2004. Using paternal occupational histories reported by mothers via telephone interview, jobs were systematically classified into 63 groups based on shared exposure profiles within occupation and industry. Data were analysed using bayesian logistic regression with a hierarchical prior for dependent shrinkage to stabilise estimation with sparse data. Several occupations were associated with an increased prevalence of various birth defect categories, including mathematical, physical and computer scientists; artists; photographers and photo processors; food service workers; landscapers and groundskeepers; hairdressers and cosmetologists; office and administrative support workers; sawmill workers; petroleum and gas workers; chemical workers; printers; material moving equipment operators; and motor vehicle operators. Findings from this study might be used to identify specific occupations worthy of further investigation and to generate hypotheses about chemical or physical exposures common to such occupations.

  1. Paternal occupation and birth defects: findings from the National Birth Defects Prevention Study

    PubMed Central

    Desrosiers, Tania A.; Herring, Amy H.; Shapira, Stuart K.; Hooiveld, Mariette; Luben, Tom J.; Herdt-Losavio, Michele L.; Lin, Shao; Olshan, Andrew F.

    2013-01-01

    Objectives Several epidemiologic studies have suggested that certain paternal occupations may be associated with an increased prevalence of birth defects in offspring. Using data from the National Birth Defects Prevention Study, we investigated the association between paternal occupation and birth defects in a case-control study of cases comprising over 60 different types of birth defects (n = 9998) and non-malformed controls (n = 4066) with dates of delivery between 1997 and 2004. Methods Using paternal occupational histories reported by mothers via telephone interview, jobs were systematically classified into 63 groups based on shared exposure profiles within occupation and industry. Data were analyzed using Bayesian logistic regression with a hierarchical prior for dependent shrinkage to stabilize estimation with sparse data. Results Several occupations were associated with an increased prevalence of various birth defect categories, including: mathematical, physical and computer scientists; artists; photographers and photo processors; food service workers; landscapers and groundskeepers; hairdressers and cosmetologists; office and administrative support workers; sawmill workers; petroleum and gas workers; chemical workers; printers; material moving equipment operators; and motor vehicle operators. Conclusions Findings from this study might be used to identify specific occupations worthy of further investigation, and to generate hypotheses about chemical or physical exposures common to such occupations. PMID:22782864

  2. Prevention of arthritis markers in experimental animal and inflammation signalling in macrophage by Karanjin isolated from Pongamia pinnata seed extract.

    PubMed

    Bose, Madhura; Chakraborty, Mousumi; Bhattacharya, Sourav; Mukherjee, Debarati; Mandal, Suvra; Mishra, Roshnara

    2014-08-01

    Karanjin, the furanoflavonoid reported to possess gastroprotective and anti-diabetic properties, was investigated against experimental arthritis and its molecular signalling in inflammation was explored in macrophages. Karanjin was isolated from hexane extract of Pongamia pinnata seeds and was evaluated on arthritis markers in adjuvant induced arthritis model (AIA) in two doses (per oral; 10 mg/kg/day and 20 mg/kg/day). Karanjin dose dependently reduced collagen and cartilage breakdown markers viz. urinary hydroxyproline and glucosamine, respectively, serum lysosomal enzymes responsible for articular cartilage damage, and major proinflammatory cytokine TNFα, secreted by macrophages involved in articular inflammation and destruction. Karanjin also prevented joint damage as evidenced from arthritis score, radiographic and histopathological analysis. To delineate the molecular target of Karanjin, in vitro study on LPS induced macrophages were performed at calibrated non toxic doses (4 µg/mL and 6 µg/mL). Karanjin reduced TNFα production and also showed potent inhibitory effect on nitric oxide and reactive oxygen species production which is generally induced by TNFα from activated macrophages. NF-κB, the key regulator of TNFα signalling during inflammation was significantly suppressed by Karanjin. Our study for the first time highlights the anti-inflammatory role of Karanjin in experimental arthritis model as well as on macrophage signalling, thereby depicting its probable mechanism of action. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Occupational health hazards to the ultrasonographer and their possible prevention.

    PubMed

    Mercer, R B; Marcella, C P; Carney, D K; McDonald, R W

    1997-05-01

    Occupational health hazards in ultrasonography are becoming more prevalent as the field continues to grow. Eye strain, musculoskeletal pain or injury, carpal tunnel syndrome, repetitive strain injuries, stress, burnout, and other hazards have been addressed as concerns in other studies and surveys. These topics are discussed, as well as the possible preventive measures that may be used to maximize and maintain the ultrasonographer's well-being throughout his or her career.

  4. Interventions for preventing occupational irritant hand dermatitis.

    PubMed

    Bauer, Andrea; Rönsch, Henriette; Elsner, Peter; Dittmar, Daan; Bennett, Cathy; Schuttelaar, Marie-Louise A; Lukács, Judit; John, Swen Malte; Williams, Hywel C

    2018-04-30

    Occupational irritant hand dermatitis (OIHD) causes significant functional impairment, disruption of work, and discomfort in the working population. Different preventive measures such as protective gloves, barrier creams and moisturisers can be used, but it is not clear how effective these are. This is an update of a Cochrane review which was previously published in 2010. To assess the effects of primary preventive interventions and strategies (physical and behavioural) for preventing OIHD in healthy people (who have no hand dermatitis) who work in occupations where the skin is at risk of damage due to contact with water, detergents, chemicals or other irritants, or from wearing gloves. We updated our searches of the following databases to January 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLlNE, and Embase. We also searched five trials registers and checked the bibliographies of included studies for further references to relevant trials. We handsearched two sets of conference proceedings. We included parallel and cross-over randomised controlled trials (RCTs) which examined the effectiveness of barrier creams, moisturisers, gloves, or educational interventions compared to no intervention for the primary prevention of OIHD under field conditions. We used the standard methodological procedures expected by Cochrane. The primary outcomes were signs and symptoms of OIHD developed during the trials, and the frequency of treatment discontinuation due to adverse effects. We included nine RCTs involving 2888 participants without occupational irritant hand dermatitis (OIHD) at baseline. Six studies, including 1533 participants, investigated the effects of barrier creams, moisturisers, or both. Three studies, including 1355 participants, assessed the effectiveness of skin protection education on the prevention of OIHD. No studies were eligible that investigated the effects of protective gloves. Among each type of intervention, there was heterogeneity concerning

  5. Moldy buildings, health of their occupants and fungal prevention.

    PubMed

    Mihinova, D; Pieckova, E

    2012-01-01

    Microscopic fungi are important biological pollutants in the indoor environment, they are spread generally: on building materials, carpets, ceiling tiles, insulations, any surfaces, wallpapers, or in heating, ventilation, and air conditioning systems. Molds are able to grow on any materials, as long as moisture and oxygen are available. Exposure to fungi in indoor environments (esp. in water-damaged buildings) can cause adverse health effects, such as allergy, asthma, hypersensitivity pneumonia, mucous membrane irritation, different toxic effects, or even mycoses (in immunocompromised individuals) - alone or in combination. As serious adverse health effects could be caused antifungal prevention is an absolute need.This review article summarizes the occurrence of fungi in the indoor environment of buildings and their contribution to occupants´ health problems, and preventive measures against molds (Tab. 1, Fig. 1, Ref. 48).

  6. Manualization of Occupational Therapy Interventions: Illustrations from the Pressure Ulcer Prevention Research Program

    PubMed Central

    Blanche, Erna Imperatore; Fogelberg, Donald; Diaz, Jesus; Carlson, Mike; Clark, Florence

    2011-01-01

    The manualization of a complex occupational therapy intervention is a crucial step in ensuring treatment fidelity for both clinical application and research purposes. Towards this latter end, intervention manuals are essential for assuring trustworthiness and replicability of randomized controlled trials (RCT’s) that aim to provide evidence of the effectiveness of occupational therapy. In this paper, literature on the process of intervention manualization is reviewed. The prescribed steps are then illustrated through our experience in implementing the University of Southern California/Rancho Los Amigos National Rehabilitation Center’s collaborative Pressure Ulcer Prevention Project (PUPP). In this research program, qualitative research provided the initial foundation for manualization of a multifaceted occupational therapy intervention designed to reduce incidence of medically serious pressure ulcers in people with SCI. PMID:22214116

  7. Inhibition of herpes simplex virus multiplication by activated macrophages: a role for arginase?

    PubMed

    Wildy, P; Gell, P G; Rhodes, J; Newton, A

    1982-07-01

    Proteose-peptone-activated mouse macrophages can prevent productive infection by herpes simplex virus in neighboring cells in vitro whether or not those cells belong to the same animal species. The effect does not require contact between the macrophages and the infected cells, may be prevented by adding extra arginine to the medium, and may be reversed when extra arginine is added 24 h after the macrophages. Arginase activity was found both intracellularly and released from the macrophages. The extracellular enzyme is quite stable; 64% activity was found after 48 h of incubation at 37 degrees C in tissue culture medium. No evidence was found that the inefficiency of virus replication in macrophages was due to self-starvation by arginase. As might be predicted macrophages can, by the same mechanism, limit productive infection by vaccinia virus.

  8. Macrophage IL-12p70 Signaling Prevents HSV-1–Induced CNS Autoimmunity Triggered by Autoaggressive CD4+ Tregs

    PubMed Central

    Mott, Kevin R.; Gate, David; Zandian, Mandana; Allen, Sariah J.; Rajasagi, Naveen Kumar; van Rooijen, Nico; Chen, Shuang; Arditi, Moshe; Rouse, Barry T.; Flavell, Richard A.; Town, Terrence; Ghiasi, Homayon

    2011-01-01

    Purpose. CD4+CD25+FoxP3+ naturally occurring regulatory T cells (Tregs) maintain self-tolerance and function to suppress overly exuberant immune responses. However, it is unclear whether innate immune cells modulate Treg function. Here the authors examined the role of innate immunity in lymphomyeloid homeostasis. Methods. The involvement of B cells, dendritic cells (DCs), macrophages, natural killer (NK) cells, and T cells in central nervous system (CNS) demyelination in different strains of mice infected ocularly with herpes simplex virus type 1 (HSV-1) was investigated. Results. The authors found that depletion of macrophages, but not DCs, B cells, NK cells, CD4+ T cells, or CD8+ T cells, induced CNS demyelination irrespective of virus or mouse strain. As with macrophage depletion, mice deficient in interleukin (IL)-12p35 or IL-12p40 showed CNS demyelination after HSV-1 infection, whereas demyelination was undetectable in HSV-1–infected, IL-23p19–deficient, or Epstein-Barr virus–induced gene 3-deficient mice. Demyelination could be rescued in macrophage-depleted mice after the injection of IL-12p70 DNA and in IL-12p35−/− or IL-12p40−/− mice after injection with IL-12p35 or IL-12p40 DNA or with recombinant viruses expressing IL-12p35 or IL-12p40. Using FoxP3-, CD4-, CD8-, or CD25-depletion and gene-deficient mouse approaches, the authors demonstrated that HSV-1–induced demyelination was blocked in the absence of CD4, CD25, or FoxP3 in macrophage-depleted mice. Flow cytometry showed an elevation of CD4+CD25+FoxP3+ T cells in the spleens of infected macrophage-depleted mice, and adoptive transfer of CD4+CD25+ T cells to infected macrophage-depleted severe combined immunodeficient mice induced CNS demyelination. Conclusions. The authors demonstrated that macrophage IL-12p70 signaling plays an important role in maintaining immune homeostasis in the CNS by preventing the development of autoaggressive CD4+ Tregs. PMID:21220560

  9. [Occupational doctors in the public prevention services and qualified occupational doctors: their roles and forms of collaboration].

    PubMed

    Taddeo, D; Di Giammarco, A M

    2006-01-01

    The occupational docters in public prevention and control services and the qualified occupational doctors who carry out functions of specialized doctors for enterprises, as well as operating according to their individual professional skills, are all part of the polydisciplinary system of collaboration that, while differing in methods, organizations and planning of their activities, have a shared aim: the safeguarding of the health and safety of the workers. The two systems have a mutual obligation to give information, foreseen also by several norms, that require common codes for evaluation and interpretation when exchanging communications, also for going beyond the simple conflictual relationship of "controller" and "controlled". In fact a shared commitment is necessary nowadays to face the lesser known and investigated risks and diseases, to promote the roles and rights of the workers, their representatives and also the employers of the micro-enterprises.

  10. Rice bran prevents high-fat diet-induced inflammation and macrophage content in adipose tissue.

    PubMed

    Justo, Maria Luisa; Claro, Carmen; Zeyda, Maximilian; Stulnig, Thomas M; Herrera, María Dolores; Rodríguez-Rodríguez, Rosalía

    2016-09-01

    The inflammatory process associated with obesity mainly arises from white adipose tissue (WAT) alterations. In the last few years, nutritional-based strategies have been positioned as promising alternatives to pharmacological approaches against these pathologies. Our aim was to determine the potential of a rice bran enzymatic extract (RBEE)-supplemented diet in the prevention of metabolic, biochemical and functional adipose tissue and macrophage changes associated with a diet-induced obesity (DIO) in mice. C57BL/6J mice were fed high-fat diet (HF), 1 and 5 % RBEE-supplemented high-fat diet (HF1 % and HF5 %, respectively) and standard diet as control. Serum cardiometabolic parameters, adipocytes size and mRNA expression of pro-inflammatory biomarkers and macrophage polarization-related genes from WAT and liver were evaluated. RBEE administration significantly decreased insulin resistance in obese mice. Serum triglycerides, total cholesterol, glucose, insulin, adiponectin and nitrites from treated mice were partially restored, mainly by 1 % RBEE-enriched diet. The incremented adipocytes size observed in HF group was reduced by RBEE treatment, being 1 % more effective than 5 % RBEE. Pro-inflammatory biomarkers in WAT such as IL-6 and IL-1β were significantly decreased in RBEE-treated mice. Adiponectin, PPARγ, TNF-α, Emr1 or M1/M2 levels were significantly restored in WAT from HF1 % compared to HF mice. RBEE-supplemented diet attenuated insulin resistance, dyslipidemia and morphological and functional alterations of adipose tissue in DIO mice. These benefits were accompanied by a modulating effect in adipocytes secretion and some biomarkers associated with macrophage polarization. Therefore, RBEE may be considered an alternative nutritional complement over metabolic syndrome and its complications.

  11. Toxicity of mycotoxins for the rat pulmonary macrophage in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sorenson, W.G.; Gerberick, G.F.; Lewis, D.M.

    1986-04-01

    The presence of mycotoxins in grains is well documented. Workers in grain handling occupations are commonly exposed to grain dust aerosols. Work in our laboratory has shown that T-2 toxin is highly toxic to rat alveolar macrophages in vitro, causing loss of viability, release of radiolabeled chromium, inhibition of macromolecular synthesis, inhibition of phagocytosis, and inhibition of macrophage activation. Similarly, patulin caused a significant release of radiolabeled chromium, decrease in ATP levels, significant inhibition of protein and RNA synthesis, and inhibition of phagocytosis. The data show that both T-2 toxin and patulin are highly toxic to rat alveolar macrophages inmore » vitro. The data further suggest that the presence of these mycotoxins in airborne respirable dust might present a hazard to exposed workers.« less

  12. An ergonomics approach model to prevention of occupational musculoskeletal injuries.

    PubMed

    Koltan, Altan

    2009-01-01

    The objective of this study was to prevent occupational musculoskeletal injuries. Our workers stacked boxes of ceramics weighing 10-27 kg, making low back pain common in our enterprise. In all the stacking stations, recommended weight limits (RWL) were separately calculated using the revised National Institute for Occupational Health lifting equation. Since the boxes weighed significantly more than the RWL, we developed a new ergonomic design that completely changed the stacking process. The load put on the workers' waist vertebrae in the new and the old stacking methods was compared to evaluate the success of the new ergonomic design, using Newton's third law of motion. Thanks to the new ergonomic design, the load on the workers' vertebrae decreased by 80%. Due to its simple technology and its very low cost compared to robots, the new ergonomic design can be commonly used in enterprises with repeated and constraining stacking.

  13. Inhibition of herpes simplex virus multiplication by activated macrophages: a role for arginase?

    PubMed Central

    Wildy, P; Gell, P G; Rhodes, J; Newton, A

    1982-01-01

    Proteose-peptone-activated mouse macrophages can prevent productive infection by herpes simplex virus in neighboring cells in vitro whether or not those cells belong to the same animal species. The effect does not require contact between the macrophages and the infected cells, may be prevented by adding extra arginine to the medium, and may be reversed when extra arginine is added 24 h after the macrophages. Arginase activity was found both intracellularly and released from the macrophages. The extracellular enzyme is quite stable; 64% activity was found after 48 h of incubation at 37 degrees C in tissue culture medium. No evidence was found that the inefficiency of virus replication in macrophages was due to self-starvation by arginase. As might be predicted macrophages can, by the same mechanism, limit productive infection by vaccinia virus. PMID:6286497

  14. NLRX1 prevents mitochondrial induced apoptosis and enhances macrophage antiviral immunity by interacting with influenza virus PB1-F2 protein

    PubMed Central

    Jaworska, Joanna; Coulombe, François; Downey, Jeffrey; Tzelepis, Fanny; Shalaby, Karim; Tattoli, Ivan; Berube, Julie; Rousseau, Simon; Martin, James G.; Girardin, Stephen E.; McCullers, Jonathan A.; Divangahi, Maziar

    2014-01-01

    To subvert host immunity, influenza A virus (IAV) induces early apoptosis in innate immune cells by disrupting mitochondria membrane potential via its polymerase basic protein 1-frame 2 (PB1-F2) accessory protein. Whether immune cells have mechanisms to counteract PB1-F2–mediated apoptosis is currently unknown. Herein, we define that the host mitochondrial protein nucleotide-binding oligomerization domain-like receptor (NLR)X1 binds to viral protein PB1-F2, preventing IAV-induced macrophage apoptosis and promoting both macrophage survival and type I IFN signaling. We initially observed that Nlrx1-deficient mice infected with IAV exhibited increased pulmonary viral replication, as well as enhanced inflammatory-associated pulmonary dysfunction and morbidity. Analysis of the lungs of IAV-infected mice revealed markedly enhanced leukocyte recruitment but impaired production of type I IFN in Nlrx1−/− mice. Impaired type I IFN production and enhanced viral replication was recapitulated in Nlrx1−/− macrophages and was associated with increased mitochondrial mediated apoptosis. Through gain- and loss-of-function strategies for protein interaction, we identified that NLRX1 directly bound PB1-F2 in the mitochondria of macrophages. Using a recombinant virus lacking PB1-F2, we confirmed that deletion of PB1-F2 abrogated NLRX1-dependent macrophage type I IFN production and apoptosis. Thus, our results demonstrate that NLRX1 acts as a mitochondrial sentinel protecting macrophages from PB1-F2–induced apoptosis and preserving their antiviral function. We further propose that NLRX1 is critical for macrophage immunity against IAV infection by sensing the extent of viral replication and maintaining a protective balance between antiviral immunity and excessive inflammation within the lungs. PMID:24799673

  15. The Dipeptidyl Peptidases 4, 8, and 9 in Mouse Monocytes and Macrophages: DPP8/9 Inhibition Attenuates M1 Macrophage Activation in Mice.

    PubMed

    Waumans, Yannick; Vliegen, Gwendolyn; Maes, Lynn; Rombouts, Miche; Declerck, Ken; Van Der Veken, Pieter; Vanden Berghe, Wim; De Meyer, Guido R Y; Schrijvers, Dorien; De Meester, Ingrid

    2016-02-01

    Atherosclerosis remains the leading cause of death in Western countries. Dipeptidyl peptidase (DPP) 4 has emerged as a novel target for the prevention and treatment of atherosclerosis. Family members DPP8 and 9 are abundantly present in macrophage-rich regions of atherosclerotic plaques, and DPP9 inhibition attenuates activation of human M1 macrophages in vitro. Studying this family in a mouse model for atherosclerosis would greatly advance our knowledge regarding their potential as therapeutic targets. We found that DPP4 is downregulated during mouse monocyte-to-macrophage differentiation. DPP8 and 9 expression seems relatively low in mouse monocytes and macrophages. Viability of primary mouse macrophages is unaffected by DPP4 or DPP8/9 inhibition. Importantly, DPP8/9 inhibition attenuates macrophage activation as IL-6 secretion is significantly decreased. Mouse macrophages respond similarly to DPP inhibition, compared to human macrophages. This shows that the mouse could become a valid model species for the study of DPPs as therapeutic targets in atherosclerosis.

  16. Role of Occupational Therapy in Preventing Work-Related Musculoskeletal Disorders With Recycling Workers: A Pilot Study.

    PubMed

    Fisher, Thomas

    Little is known about injury prevention in recycling workers; therefore, in this study, I aimed to identify physical and psychosocial risk factors for employees involved in single-stream recycling and to explore strategies for prevention and wellness. Fifteen participants who were either recycling workers or supervisors located throughout seven locations on an urban university campus participated. A mixed-methods research design was used to obtain data through a variety of standardized work environment and health questionnaires and semistructured interviews. Approximately 80% of participants expressed satisfaction with their jobs; 50% reported having a musculoskeletal injury; and 33% reported a lack of support from coworkers or supervisors, which created stress and anxiety. Additional risk factors included poor body mechanics, equipment issues, poor social interactions, and lack of supervisor knowledge for prevention. Occupational therapy practitioners are well situated to support preventive interventions that address the combined physical and psychosocial needs of recycling workers. Copyright © 2017 by the American Occupational Therapy Association, Inc.

  17. [Use of hypertext as information and training tools in the prevention of occupational risk].

    PubMed

    Franco, G

    1998-01-01

    Modern medical education is based on a variety of teaching techniques, by means of which individuals learn most effectively. The availability of the new technologies together with the diffusion of personal computers is favouring the spreading of the use of hypertexts through the World Wide Web. This contribution describes 2 hypertexts ("Human Activities and Health Risk"; "Occupation, Risk and Disease. A Problem-Oriented Hypertext-Tool to Learn Occupational Medicine") and the prototype "Virtual Hospital". Assuming that prevention of health risks is based upon their knowledge, they have been created with the aim of providing users with problem-oriented tools, whose retorical aspects (content, information organization, user interface) are analysed. The "Human Activities and Health Risk" deals with the description of working activities and allows user to recognize health risks. The "Occupation, Risk and Disease. A Problem-Oriented Hypertext-Tool to Learn Occupational Medicine" embodies a case report containing the clustered information about the patient and the library including educational material (risk factors, symptoms and signs, organ system diseases, jobs, occupational risk factors, environment related diseases. The "Virtual Hospital" has been conceived assuming that an appropriate information can change workers' behaviour in hospital, where health risks can be often underevaluated. It consists of a variety of structured and unstructured information, which can be browsed by users, allowing the discovery of links and providing the awareness of the semantic relationship between related information elements (including environment, instruments, drugs, job analysis, situations at risk for health, preventive means). The "Virtual Hospital" aims making the understanding of the working situations at risk easier and more interesting, stimulating the awareness of the relationship between jobs and risks.

  18. CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages.

    PubMed

    Meziani, Lydia; Mondini, Michele; Petit, Benoît; Boissonnas, Alexandre; Thomas de Montpreville, Vincent; Mercier, Olaf; Vozenin, Marie-Catherine; Deutsch, Eric

    2018-03-01

    Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration.We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation.High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF. In the preclinical model, upregulation of T-helper (Th)2 cytokines was measured, whereas Th1 cytokines were downregulated in RIF tissue lysate. Bronchoalveolar lavage demonstrated upregulation of both types of cytokines. At steady state, tissue-infiltrating macrophages (IMs) expressed 10-fold more arginase (Arg)-1 than alveolar macrophages (AMs), and a 40-fold upregulation of Arg-1 was found in IMs isolated from RIF. IMs, but not AMs, were able to induce myofibroblast activation in vitro In addition, whereas depletion of AMs using Clodrosome didn't affect RIF score, depletion of IMs using a clinically available colony-stimulating factor receptor-1 (CSF1R) neutralising antibody was antifibrotic.These findings suggest differential contributions of alveolar versus interstitial macrophages in RIF, highlighting the fibrogenic role of IMs. The CSF1/CSF1R pathway was identified as a new therapeutic target to inhibit RIF. Copyright ©ERS 2018.

  19. Are you prepared? Defining occupational health resource needs to prevent infectious disease transmission in the health care sector.

    PubMed

    Pollock, S L; Yassi, A; Connell, I; Gamage, B; Copes, R

    2009-01-01

    This article discusses the extent of resource allocation to Occupational Health (OH) to prevent infectious disease exposure and transmission in British Columbia (B.C.). It also characterizes the delineation of roles and responsibilities within OH services in B.C. health care settings and highlights areas where improvements to current OH programs could be made to prevent and control occupational infections. Given the breadth of OH responsibilities, resource allocation in many health care institutions for these services is inadequate and roles and responsibilities may not be clearly delineated.

  20. Occupational asthma: a review.

    PubMed Central

    Lombardo, L J; Balmes, J R

    2000-01-01

    Occupational asthma is the most common form of occupational lung disease in the developed world at the present time. In this review, the epidemiology, pathogenesis/mechanisms, clinical presentations, management, and prevention of occupational asthma are discussed. The population attributable risk of asthma due to occupational exposures is considerable. Current understanding of the mechanisms by which many agents cause occupational asthma is limited, especially for low-molecular-weight sensitizers and irritants. The diagnosis of occupational asthma is generally established on the basis of a suggestive history of a temporal association between exposure and the onset of symptoms and objective evidence that these symptoms are related to airflow limitation. Early diagnosis, elimination of exposure to the responsible agent, and early use of inhaled steroids may play important roles in the prevention of long-term persistence of asthma. Persistent occupational asthma is often associated with substantial disability and consequent impacts on income and quality of life. Prevention of new cases is the best approach to reducing the burden of asthma attributable to occupational exposures. Future research needs are identified. PMID:10931788

  1. Macrophage Phenotype Modulation by CXCL4 in Atherosclerosis.

    PubMed

    Gleissner, Christian A

    2012-01-01

    During atherogenesis, blood monocytes transmigrate into the subendothelial space and differentiate toward macrophages and foam cells. The major driver of monocyte-macrophage differentiation is macrophage colony-stimulating factor (M-CSF). M-CSF-induced macrophages are important promoters of atherogenesis as demonstrated in M-CSF and M-CSF receptor knock out mice. However, M-CSF is not the only relevant promoter of macrophage differentiation. The platelet chemokine CXCL4 also prevents monocyte apoptosis and promotes macrophage differentiation in vitro. It is secreted from activated platelets and has effects on various cell types relevant in atherogenesis. Knocking out the Pf4 gene coding for CXCL4 in Apoe(-/-) mice leads to reduced atherogenesis. Thus, it seems likely that CXC4-induced macrophages may have specific pro-atherogenic capacities. We have studied CXC4-induced differentiation of human macrophages using gene chips, systems biology, and functional in vitro and ex vivo experiments. Our data indicate that CXCL4-induced macrophages are distinct from both their M-CSF-induced counterparts and other known macrophage polarizations like M1 macrophages (induced by lipopolysaccharide and interferon-gamma) or M2 macrophages (induced by interleukin-4). CXCL4-induced macrophages have distinct phenotypic and functional characteristics, e.g., the complete loss of the hemoglobin-haptoglobin (Hb-Hp) scavenger receptor CD163 which is necessary for effective hemoglobin clearance after plaque hemorrhage. Lack of CD163 is accompanied by the inability to upregulate the atheroprotective enzyme heme oxygenase-1 in response to Hb-Hp complexes. This review covers the current knowledge about CXCL4-induced macrophages. Based on their unique properties, we have suggested to call these macrophages "M4." CXCL4 may represent an important orchestrator of macrophage heterogeneity within atherosclerotic lesions. Further dissecting its effects on macrophage differentiation may help to

  2. Macrophage Phenotype Modulation by CXCL4 in Atherosclerosis

    PubMed Central

    Gleissner, Christian A.

    2011-01-01

    During atherogenesis, blood monocytes transmigrate into the subendothelial space and differentiate toward macrophages and foam cells. The major driver of monocyte–macrophage differentiation is macrophage colony-stimulating factor (M-CSF). M-CSF-induced macrophages are important promoters of atherogenesis as demonstrated in M-CSF and M-CSF receptor knock out mice. However, M-CSF is not the only relevant promoter of macrophage differentiation. The platelet chemokine CXCL4 also prevents monocyte apoptosis and promotes macrophage differentiation in vitro. It is secreted from activated platelets and has effects on various cell types relevant in atherogenesis. Knocking out the Pf4 gene coding for CXCL4 in Apoe−/− mice leads to reduced atherogenesis. Thus, it seems likely that CXC4-induced macrophages may have specific pro-atherogenic capacities. We have studied CXC4-induced differentiation of human macrophages using gene chips, systems biology, and functional in vitro and ex vivo experiments. Our data indicate that CXCL4-induced macrophages are distinct from both their M-CSF-induced counterparts and other known macrophage polarizations like M1 macrophages (induced by lipopolysaccharide and interferon-gamma) or M2 macrophages (induced by interleukin-4). CXCL4-induced macrophages have distinct phenotypic and functional characteristics, e.g., the complete loss of the hemoglobin–haptoglobin (Hb–Hp) scavenger receptor CD163 which is necessary for effective hemoglobin clearance after plaque hemorrhage. Lack of CD163 is accompanied by the inability to upregulate the atheroprotective enzyme heme oxygenase-1 in response to Hb–Hp complexes. This review covers the current knowledge about CXCL4-induced macrophages. Based on their unique properties, we have suggested to call these macrophages “M4.” CXCL4 may represent an important orchestrator of macrophage heterogeneity within atherosclerotic lesions. Further dissecting its effects on macrophage differentiation may

  3. Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

    PubMed Central

    Baci, Denisa; Tremolati, Marco; Fanuli, Matteo; Farronato, Giampietro; Mortara, Lorenzo

    2018-01-01

    Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy. PMID:29507865

  4. 41 CFR 102-74.360 - What are the specific accident and fire prevention responsibilities of occupant agencies?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... appropriate fire safety precautions in their work; (i) Keep facilities in the safest condition practicable... accident and fire prevention responsibilities of occupant agencies? 102-74.360 Section 102-74.360 Public... MANAGEMENT REGULATION REAL PROPERTY 74-FACILITY MANAGEMENT Facility Management Accident and Fire Prevention...

  5. 41 CFR 102-74.360 - What are the specific accident and fire prevention responsibilities of occupant agencies?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... appropriate fire safety precautions in their work; (i) Keep facilities in the safest condition practicable... accident and fire prevention responsibilities of occupant agencies? 102-74.360 Section 102-74.360 Public... MANAGEMENT REGULATION REAL PROPERTY 74-FACILITY MANAGEMENT Facility Management Accident and Fire Prevention...

  6. 41 CFR 102-74.360 - What are the specific accident and fire prevention responsibilities of occupant agencies?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... appropriate fire safety precautions in their work; (i) Keep facilities in the safest condition practicable... accident and fire prevention responsibilities of occupant agencies? 102-74.360 Section 102-74.360 Public... MANAGEMENT REGULATION REAL PROPERTY 74-FACILITY MANAGEMENT Facility Management Accident and Fire Prevention...

  7. Analysis of appeals against the ruling of occupational physicians lodged with the Prevention and Occupational Epidemiology Operative Unit, ASP Palermo (Palermo Health Authority), from 2008-2010.

    PubMed

    Marsala, Maria Grazia Laura; Morici, Mariagrazia; Anastasi, Giovanna; Costantino, C; Tramuto, F; Lacca, G; Curcurù, Loredana; Costagliola, E; Ilardo, Sara; Trapani, Elisa; Caracausi, Rosa; Firenze, A

    2013-01-01

    The responsibility of the Department for Prevention and Safety at the workplace of the Palermo Health Authority (ASP) is to monitor and coordinate the activity of occupational physicians operating in Palermo and its province. One of its obligations is to examine appeals "against the judgment of occupational physicians", "..and, after carrying out further investigation, confirm, modify or reverse the ruling itself" (art. 41, par. 6, legislative Decree 81/08). The purpose of this study was to analyze the appeals lodged against a judgment of fitness for work" submitted to the "Health Prevention and Occupational Epidemiology Operative Unit" of the Department of Prevention and Safety at the Workplace of the ASP Palermo, from 2008 to 2010. The total number of appeals lodged during the three-year period was 211, 174 of which were finalized. The most frequent job category among the appellants was that of blue-collar workers, in various sectors, covering 44.5% of the subjects under study (93 cases). In 64.2% of the processed appeals (131 cases), the judgment of the physician was modified, while in the remaining 36.8% (73 cases) it was confirmed. The work fitness judgment with restrictions was the category against which most appeals were lodged, and the diseases in question mostly concerned the osteoarticular and cardiovascular systems. In a context of continuous change in the labour field and the related risks to the health and safety of workers, the occupational physician must approach the worker in a comprehensive manner, through an assessment of the possible health problems and the working environment in which he/she operates.

  8. [An analysis of appeals against the ruling of the occupational physician's lodged to the Department of Prevention and Safety in the Working Environment--Health Prevention and Occupational Epidemiology Operative Unit within the A.S.P. Palermo (Palermo Health Authority), years 2008-2010].

    PubMed

    Marsala, M G L; Morici, M; Lacca, G; Curcurù, L; Eduardo, E Costagliola; Ilardo, S; Trapani, E; Caracausi, R; Firenze, A

    2012-01-01

    The purpose of this study is to analyze the appeals against a "suitability judgment for work" lodged to the U.O.S. "Health Prevention and Occupational Epidemiology Operative Unit" of Department of Prevention and Safety in the Working Environment within the ASP Palermo (U.O.S.), from 2008 to 2010. Studying the appeals gives an indirect view on the occupational physician activity and allows to monitor their actions, analysis aims at highlighting those issues around which any planning and implementation of coordination activities should be focused.

  9. Occupational contact dermatitis.

    PubMed

    Lushniak, Boris D

    2004-01-01

    The dermatologist should be aware of the many facets of occupational skin diseases, which can be caused by physical, chemical, and biological insults. The most common manifestation of occupational skin diseases is contact dermatitis (both irritant and allergic). Three factors point out the importance of occupational skin diseases as diseases that have a public health impact: 1) occupational skin diseases are common; 2) they often have a poor prognosis; and 3) they result in a noteworthy economic impact for society and for an individual. They are also diseases amenable to public health interventions. Specific industries and exposures may put a worker at risk of occupational contact dermatitis. The accuracy of the diagnosis of occupational contact dermatitis is related to the skill level, experience, and knowledge of the medical professional who makes the diagnosis and confirms the relationship with a workplace exposure. Prevention of occupational contact dermatitis is important, and a variety of prevention strategies are available.

  10. [An analysis of status of personnel in occupational disease prevention and treatment institutions in Hunan Province, China, from 1996 to 2015].

    PubMed

    Liu, X L; Xiao, Y L; Tang, H Q; Chen, B L; Yang, L H; Xiao, Y L; Lv, S J

    2018-01-20

    Objective: To analyze the status of personnel in occupational disease prevention and treatment institutions in Hunan Province, China, from 1996 to 2015, to predict staff composition using grey model (GM) (1, 1) , and to provide a scientific basis and reference for optimizing human resource planning of occupational disease prevention and treatment in other provinces and regions and promoting the service capacity of the institutions. Methods: The data of the staff in occupational disease prevention and treatment institutions in Hunan Province, China, from 1996 to 2015 were obtained from the established basic information management system. The descriptive analysis method was used to analyze the dynamic changes in number and composition of the staff and the GM (1, 1) was used to predict the staff composition. Results: The numbers of the staff members in 1996 and 2015 in occupational disease prevention and treatment institutions in Hunan Province, China were 1591 and 1429, respectively. In the twenty years, the main education level of the staff transformed from "technical secondary school education and non-academic qualifications" to "bachelor degree or above and college degree"; the main major of the staff transformed from "other majors" to "public health and clinical medicine"; the proportion of the staff members without professional titles changed from >1/3 to 5%; and the proportions of the staff members with senior, intermediate, and junior professional titles were steadily rising. GM prediction showed that the proportions of highly educated staff members in 2018 and 2020 would be up to 41.00% and 45.61%, respectively; and the proportions of the staff members with a major in public health in 2018 and 2020 would be up to 44.15% and 46.60%, respectively. Conclusion: The staff in occupational disease prevention and treatment institutions in Hunan Province, China, in the twenty years have slight changes in staff size and great improvement in staff quality, which is

  11. 41 CFR 102-74.360 - What are the specific accident and fire prevention responsibilities of occupant agencies?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... other hanging materials that are made of non-combustible or flame-resistant fabric; (f) Use only... resistant; (g) Cooperate with GSA to develop and maintain fire prevention programs that provide the maximum... accident and fire prevention responsibilities of occupant agencies? 102-74.360 Section 102-74.360 Public...

  12. Macrophage Mitochondrial Oxidative Stress Promotes Atherosclerosis and NF-κB-Mediated Inflammation in Macrophages

    PubMed Central

    Wang, Ying; Wang, Gary Z.; Rabinovitch, Peter S.; Tabas, Ira

    2014-01-01

    Rationale Mitochondrial oxidative stress (mitoOS) has been shown to correlate with the progression of human atherosclerosis. However, definitive cell-type specific causation studies in vivo are lacking, and the molecular mechanisms of potential pro-atherogenic effects remain to be determined. Objective To assess the importance of macrophage mitoOS in atherogenesis and explore the underlying molecular mechanisms. Methods & Results We first validated Western-type diet-fed Ldlr-/- mice as a model of human mitoOS-atherosclerosis association by showing that a marker of mitoOS in lesional macrophages, non-nuclear oxidative DNA damage, correlates with aortic root lesion development. To investigate the importance of macrophage-mitoOS, we used a genetic engineering strategy in which the OS suppressor catalase was ectopically expressed in mitochondria (mCAT) in macrophages. MitoOS in lesional macrophages was successfully suppressed in these mice, and this led to a significant reduction in aortic root lesional area. The mCAT lesions had less monocyte-derived cells, less Ly6chi monocyte infiltration into lesions, and lower levels of the monocyte chemotactic protein-1 (MCP-1). The decrease in lesional MCP-1 was associated with suppression of other markers of inflammation and with decreased phosphorylation of RelA (NF-κB p65), indicating decreased activation of the pro-inflammatory NF-κB pathway. Using models of mitoOS in cultured macrophages, we showed that mCAT suppressed MCP-1 expression by decreasing activation of the Iκ-kinase-RelA NF-κB pathway. Conclusions MitoOS in lesional macrophages amplifies atherosclerotic lesion development by promoting NF-κB-mediated entry of monocytes and other inflammatory processes. In view of the mitoOS-atherosclerosis link in human atheromata, these findings reveal a potentially new therapeutic target to prevent the progression of atherosclerosis. PMID:24297735

  13. Prioritizing industries for occupational injury and illness prevention and research, Washington State Workers' compensation claims, 1999-2003.

    PubMed

    Bonauto, David; Silverstein, Barbara; Adams, Darrin; Foley, Michael

    2006-08-01

    The objective of this study was to identify high-risk industry groups for effective allocation of occupational safety and health prevention and research resources. We used all compensable Washington state workers' compensation claims to rank North American Industry Classification System (NAICS) industry groups by a "prevention index" (PI). The PI is the average of the rank orders of each industry group's claim count and claim incidence rate. Of the 274 industry groups ranked by PI for all compensable workers' compensation claims, the following industry groups ranked the highest: NAICS 2381 Foundation, Structure, and Building Exterior Contractors, NAICS 4841 General Freight Trucking, and NAICS 2361 Residential Building Construction. Industry group PI rankings are reported for the seven most common costly occupational injury types. Use of a PI can focus prevention and research resources where they can be of most benefit.

  14. [Role of specialized care services of the national health service in the new framework for the prevention of occupational risks (I)].

    PubMed

    Goicoechea-Iribarren, J M

    The Spanish constitution and other legal provisions reflect the need to guarantee the health and security of workers at work. The Prevention of Industrial Risks Act incorporates this mandate and suggests a new model of prevention based on continued control of risk, participation of the workers and their education, and different modes of prevention management are set out. The objective of occupational medicine covers four areas: environment (evaluation of posts, teams, dangerous substances, etc.), health (vigilance of professional illness), emergencies and information and documentation (confidentiality). At present the task of the occupational doctor is hampered by (a) The polarization of prevention: the effort to reduce the high rate of accidents and permissiveness with regard to professional illness. (b) Complementary investigations: the lack of specialist reference services which supervise the health of the workers. (c) Minimal development in small and medium size businesses: The National Health System phagocytes industrial diseases, erroneously labelled as ordinary illness. (1) The medical training of all specialists should include a period dedicated to the study of occupational diseases and work as a source of health problems. (2) To improve the coordination between the occupational doctor and the Primary Care doctor, the creation of specialist reference services for occupational illnesses, by means of the National Health Service or the Mutual Aid Societies of occupational accidents and professional illnesses so as to refer suspected cases to them. (3) To emphasize the clinical history, evaluating the principle of Hipocrates. (4) To take into account sentry pathology in conditions of unknown origin. (5) To make a specific control of the health of all workers, particularly those who work with dangerous products or substances.

  15. Occupational mental health promotion: a prevention agenda based on education and treatment. The American Psychological Association/National Institute for Occupational Safety and Health, Health Promotion Panel, 1990 Work and Well-Being Conference.

    PubMed

    1992-01-01

    PURPOSE OF THE REVIEW. Psychological disorders are one of the 10 leading work-related diseases and injuries in the United States according to the National Institute for Occupational Safety and Health. This article addresses occupational metal health and preventive stress management in the workplace. The individual and organizational costs are briefly considered with concern for reducing the burden of suffering associated with these problems. SEARCH METHOD. As an American Psychological Association interdisciplinary panel, we searched the psychological, medical, public health, and organizational literature. We selected articles relevant to the problem of psychological disorders in the workplace and to enhancing occupational mental health and preventive stress management. IMPORTANT FINDINGS. The panel proposed a national agenda of education and treatment, combined with a program of evaluation research, for addressing these issues. Target populations are identified, and the need for collaboration among a variety of national constituencies is considered. Advancing occupational mental health and promoting skills in preventive stress management is considered in the context of comprehensive health promotion. MAJOR CONCLUSIONS. The panel concluded that there is a pressing need to: 1) set a 'gold' standard concerning the current state of knowledge in the domains of occupational mental health and stress management; 2) identify Diagnostically Related Groups (DRGs) which are stress-related; 3) establish assessment standards for stress and mental health; 4) set guidelines for reasonable interventions; and 5) establish acceptable post-outcome criteria.

  16. Agents of Change: The Role of Healthcare Workers in the Prevention of Nosocomial and Occupational Tuberculosis

    PubMed Central

    Nathavitharana, Ruvandhi R.; Bond, Patricia; Dramowski, Angela; Kotze, Koot; Lederer, Philip; Oxley, Ingrid; Peters, Jurgens A.; Rossouw, Chanel; van der Westhuizen, Helene-Mari; Willems, Bart; Ting, Tiong Xun; von Delft, Arne; von Delft, Dalene; Duarte, Raquel; Nardell, Edward; Zumla, Alimuddin

    2018-01-01

    Healthcare workers (HCWs) play a central role in global tuberculosis (TB) elimination efforts but their contributions are undermined by occupational TB. HCWs have higher rates of latent and active TB than the general population due to persistent occupational TB exposure, particularly in settings where there is a high prevalence of undiagnosed TB in healthcare facilities and TB infection control (TB-IC) programmes are absent or poorly implemented. Occupational health programmes in high TB burden settings are often weak or non-existent and thus data that record the extent of the increased risk of occupational TB globally are scarce. HCWs represent a limited resource in high TB burden settings and occupational TB can lead to workforce attrition. Stigma plays a role in delayed diagnosis, poor treatment outcomes and impaired wellbeing in HCWs who develop TB. Ensuring the prioritization and implementation of TB-IC interventions and occupational health programmes, which include robust monitoring and evaluation, is critical to reduce nosocomial TB transmission to patients and HCWs. The provision of preventive therapy for HCWs with latent TB infection can also prevent progression to active TB. Unlike other patient groups, HCWs are in a unique position to serve as agents of change to raise awareness, advocate for necessary resource allocation and implement TB-IC interventions, with appropriate support from dedicated TB-IC officers at the facility and national TB programme level. Students and community health workers (CHWs) must be engaged and involved in these efforts. Nosocomial TB transmission is an urgent public health problem and adopting rights-based approaches can be helpful. However, these efforts cannot succeed without increased political will, supportive legal frameworks and financial investments to support HCWs in efforts to decrease TB transmission. PMID:28256382

  17. Agents of change: The role of healthcare workers in the prevention of nosocomial and occupational tuberculosis.

    PubMed

    Nathavitharana, Ruvandhi R; Bond, Patricia; Dramowski, Angela; Kotze, Koot; Lederer, Philip; Oxley, Ingrid; Peters, Jurgens A; Rossouw, Chanel; van der Westhuizen, Helene-Mari; Willems, Bart; Ting, Tiong Xun; von Delft, Arne; von Delft, Dalene; Duarte, Raquel; Nardell, Edward; Zumla, Alimuddin

    2017-03-01

    Healthcare workers (HCWs) play a central role in global tuberculosis (TB) elimination efforts but their contributions are undermined by occupational TB. HCWs have higher rates of latent and active TB than the general population due to persistent occupational TB exposure, particularly in settings where there is a high prevalence of undiagnosed TB in healthcare facilities and TB infection control (TB-IC) programmes are absent or poorly implemented. Occupational health programmes in high TB burden settings are often weak or non-existent and thus data that record the extent of the increased risk of occupational TB globally are scarce. HCWs represent a limited resource in high TB burden settings and occupational TB can lead to workforce attrition. Stigma plays a role in delayed diagnosis, poor treatment outcomes and impaired well-being in HCWs who develop TB. Ensuring the prioritization and implementation of TB-IC interventions and occupational health programmes, which include robust monitoring and evaluation, is critical to reduce nosocomial TB transmission to patients and HCWs. The provision of preventive therapy for HCWs with latent TB infection (LTBI) can also prevent progression to active TB. Unlike other patient groups, HCWs are in a unique position to serve as agents of change to raise awareness, advocate for necessary resource allocation and implement TB-IC interventions, with appropriate support from dedicated TB-IC officers at the facility and national TB programme level. Students and community health workers (CHWs) must be engaged and involved in these efforts. Nosocomial TB transmission is an urgent public health problem and adopting rights-based approaches can be helpful. However, these efforts cannot succeed without increased political will, supportive legal frameworks and financial investments to support HCWs in efforts to decrease TB transmission. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Organisational Factors of Occupational Accidents with Movement Disturbance (OAMD) and Prevention

    PubMed Central

    LECLERCQ, Sylvie

    2014-01-01

    Workplace design and upkeep, or human factors, are frequently advanced for explaining so-called Occupational Slip, Trip and Fall Accidents (OSTFAs). Despite scientific progress, these accidents, and more broadly Occupational Accidents with Movement Disturbance (OAMDs), are also commonly considered to be “simple”. This paper aims to stimulate changes in such perceptions by focusing on organisational factors that often combine with other accident factors to cause movement disturbance and injury in work situations. These factors frequently lead to arbitration between production and safety, which involves implementation of controls by workers. These controls can lead to greater worker exposure to OAMD risk. We propose a model that focuses on such controls to account specifically for the need to confront production and safety logics within a company and to enhance the potential for appropriate prevention action. These are then integrated into the set of controls highlighted by work organisation model developed by the NIOSH. PMID:25345425

  19. Preventive effects of heregulin-beta1 on macrophage foam cell formation and atherosclerosis.

    PubMed

    Xu, Gang; Watanabe, Takuya; Iso, Yoshitaka; Koba, Shinji; Sakai, Tetsuo; Nagashima, Masaharu; Arita, Shigeko; Hongo, Shigeki; Ota, Hidekazu; Kobayashi, Youichi; Miyazaki, Akira; Hirano, Tsutomu

    2009-08-28

    Human heregulins, neuregulin-1 type I polypeptides that activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, are expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester accumulation, is modulated by scavenger receptor class A (SR-A), acyl-coenzyme A:cholesterol acyltransferase (ACAT)1, and ATP-binding cassette transporter (ABC)A1. The present study clarified the roles of heregulins in macrophage foam cell formation and atherosclerosis. Plasma heregulin-beta(1) levels were significantly decreased in 31 patients with acute coronary syndrome and 33 patients with effort angina pectoris compared with 34 patients with mild hypertension and 40 healthy volunteers (1.3+/-0.3, 2.0+/-0.4 versus 7.6+/-1.4, 8.2+/-1.2 ng/mL; P<0.01). Among all patients with acute coronary syndrome and effort angina pectoris, plasma heregulin-beta(1) levels were further decreased in accordance with the severity of coronary artery lesions. Expression of heregulin-beta(1) was observed at trace levels in intracoronary atherothrombosis obtained by aspiration thrombectomy from acute coronary syndrome patients. Heregulin-beta(1), but not heregulin-alpha, significantly reduced acetylated low-density lipoprotein-induced cholesterol ester accumulation in primary cultured human monocyte-derived macrophages by reducing SR-A and ACAT1 expression and by increasing ABCA1 expression at both mRNA and protein levels. Heregulin-beta(1) significantly decreased endocytic uptake of [(125)I]acetylated low-density lipoprotein and ACAT activity, and increased cholesterol efflux to apolipoprotein (Apo)A-I from human macrophages. Chronic infusion of heregulin-beta(1) into ApoE(-/-) mice significantly suppressed the development of atherosclerotic lesions. This study provided the first evidence that heregulin-beta(1) inhibits atherogenesis and suppresses macrophage foam cell formation via SR

  20. Occupational exposures to human immunodeficiency virus, hepatitis B virus, and hepatitis C virus: risk, prevention, and management.

    PubMed

    Cleveland, Jennifer L; Cardo, Denise M

    2003-10-01

    Current data indicate that the risk for transmitting bloodborne pathogens in dental health care settings is low. Pre-exposure hepatitis B vaccination and the use of standard precautions to prevent exposure to blood are the most effective strategies for preventing DHCP from occupational infection with HIV, HBV or HCV. Each dental health care facility should develop a comprehensive written program for preventing and managing occupational exposures to blood that: (1) describes the types of blood exposures that may place DHCP at risk for infection; (2) outlines procedures for promptly reporting and evaluating such exposures; and (3) identifies a health care professional who is qualified to provide counseling and perform all medical evaluations and procedures in accordance with the most current USPHS recommendations. Finally, resources should be available that permit rapid access to clinical care, testing, counseling, and PEP for exposed DHCP and the testing and counseling of source patients.

  1. Relationship of inflammatory cell cytokines to disease severity in individuals with occupational inorganic dust exposure.

    PubMed

    Rom, W N

    1991-01-01

    The pneumoconioses due to chronic occupational exposure to asbestos, coal, or silica are characterized by an alveolar macrophage-dominated alveolitis with exaggerated spontaneous release of mediators: oxidants, chemotaxins for neutrophils, and fibroblast growth factors. Bronchoalveolar lavage was performed on 66 non-smoking inorganic dust-exposed individuals with a chest x-ray greater than or equal to 1/0 stratified by presence or absence of restrictive respiratory impairment, and 28 unexposed non-smoking controls. Both dust-exposed groups stratified by presence or not of impairment had increased numbers of total cells recovered by lavage compared to normals, and those with respiratory impairment (n = 40) had a significant increase in percent and number of neutrophils recovered. Similarly, only those with respiratory impairment had macrophages that spontaneously released significant amounts of the oxidants superoxide anion and hydrogen peroxide. There was a significant trend for the release of fibronectin by macrophages from controls to dust-exposed without impairment to those with impairment. Both dust-exposed groups also had increased release of alveolar macrophage-derived progression growth factor, but this was significantly less than macrophages from patients with idiopathic pulmonary fibrosis. Since occupational exposure was virtually identical in inorganic dust-exposed individuals with versus without respiratory impairment, the quantitative differences in the release of macrophage mediators may be due to factors in host susceptibility.

  2. Nicotinamide: a vitamin able to shift macrophage differentiation toward macrophages with restricted inflammatory features.

    PubMed

    Weiss, Ronald; Schilling, Erik; Grahnert, Anja; Kölling, Valeen; Dorow, Juliane; Ceglarek, Uta; Sack, Ulrich; Hauschildt, Sunna

    2015-11-01

    The differentiation of human monocytes into macrophages is influenced by environmental signals. Here we asked in how far nicotinamide (NAM), a vitamin B3 derivative known to play a major role in nicotinamide adenine dinucleotide (NAD)-mediated signaling events, is able to modulate monocyte differentiation into macrophages developed in the presence of granulocyte macrophage colony-stimulating factor (GM-MØ) or macrophage colony-stimulating factor (M-MØ). We found that GM-MØ undergo biochemical, morphological and functional modifications in response to NAM, whereas M-MØ were hardly affected. GM-MØ exposed to NAM acquired an M-MØ-like structure while the LPS-induced production of pro-inflammatory cytokines and COX-derived eicosanoids were down-regulated. In contrast, NAM had no effect on the production of IL-10 or the cytochrome P450-derived eicosanoids. Administration of NAM enhanced intracellular NAD concentrations; however, it did not prevent the LPS-mediated drain on NAD pools. In search of intracellular molecular targets of NAM known to be involved in LPS-induced cytokine and eicosanoid synthesis, we found NF-κB activity to be diminished. In conclusion, our data show that vitamin B3, when present during the differentiation of monocytes into GM-MØ, interferes with biochemical pathways resulting in strongly reduced pro-inflammatory features. © The Author(s) 2015.

  3. Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-κB-mediated inflammation in macrophages.

    PubMed

    Wang, Ying; Wang, Gary Z; Rabinovitch, Peter S; Tabas, Ira

    2014-01-31

    Mitochondrial oxidative stress (mitoOS) has been shown to correlate with the progression of human atherosclerosis. However, definitive cell type-specific causation studies in vivo are lacking, and the molecular mechanisms of potential proatherogenic effects remain to be determined. Our aims were to assess the importance of macrophage mitoOS in atherogenesis and to explore the underlying molecular mechanisms. We first validated Western diet-fed Ldlr(-/-) mice as a model of human mitoOS-atherosclerosis association by showing that non-nuclear oxidative DNA damage, a marker of mitoOS in lesional macrophages, correlates with aortic root lesion development. To investigate the importance of macrophage mitoOS, we used a genetic engineering strategy in which the OS suppressor catalase was ectopically expressed in mitochondria (mCAT) in macrophages. MitoOS in lesional macrophages was successfully suppressed in these mice, and this led to a significant reduction in aortic root lesional area. The mCAT lesions had less monocyte-derived cells, less Ly6c(hi) monocyte infiltration into lesions, and lower levels of monocyte chemotactic protein-1. The decrease in lesional monocyte chemotactic protein-1 was associated with the suppression of other markers of inflammation and with decreased phosphorylation of RelA (NF-κB p65), indicating decreased activation of the proinflammatory NF-κB pathway. Using models of mitoOS in cultured macrophages, we showed that mCAT suppressed monocyte chemotactic protein-1 expression by decreasing the activation of the IκB-kinase β-RelA NF-κB pathway. MitoOS in lesional macrophages amplifies atherosclerotic lesion development by promoting NF-κB-mediated entry of monocytes and other inflammatory processes. In view of the mitoOS-atherosclerosis link in human atheromata, these findings reveal a potentially new therapeutic target to prevent the progression of atherosclerosis.

  4. Occupational therapists lead a national injury prevention strategy to help older drivers.

    PubMed

    Craik, Janet M

    2011-04-01

    As older adults are the fastest growing segment of the driving population, the Canadian Association of Occupational Therapists (CAOT) has taken older driver safety as a key priority. The purpose of this paper is to present the National Blueprint for Injury Prevention in Older Drivers (Blueprint) and its related activities. Since 2006, CAOT has been working on initiatives relating to the National Blueprint for Injury Prevention in Older Drivers. The most recent activities include the launch of informational brochures and a website. The Blueprint and its related activities were developed with the intent to prolong safe driving among older adults in Canada, and to propose future actions to be addressed by all stakeholders interested in older driver safety.

  5. TRPV2 has a pivotal role in macrophage particle binding and phagocytosis.

    PubMed

    Link, Tiffany M; Park, Una; Vonakis, Becky M; Raben, Daniel M; Soloski, Mark J; Caterina, Michael J

    2010-03-01

    Macrophage phagocytosis is critical for defense against pathogens. Whereas many steps of phagocytosis involve ionic flux, the underlying ion channels remain ill defined. Here we show that zymosan-, immunoglobulin G (IgG)- and complement-mediated particle binding and phagocytosis were impaired in macrophages lacking the cation channel TRPV2. TRPV2 was recruited to the nascent phagosome and depolarized the plasma membrane. Depolarization increased the synthesis of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)), which triggered the partial actin depolymerization necessary for occupancy-elicited phagocytic receptor clustering. TRPV2-deficient macrophages were also defective in chemoattractant-elicited motility. Consequently, TRPV2-deficient mice showed accelerated mortality and greater organ bacterial load when challenged with Listeria monocytogenes. Our data demonstrate the participation of TRPV2 in early phagocytosis and its fundamental importance in innate immunity.

  6. How much do workers' health examinations add to health and safety at the workplace? Occupational preventive usefulness of routine health examinations.

    PubMed

    Rodríguez-Jareño, Maria Cruz; Molinero, Emilia; de Montserrat, Jaume; Vallès, Antoni; Aymerich, Marta

    2015-01-01

    Despite no evidence in favour, routine workers' health examinations, mostly pre-employment and periodic, are extensively performed worldwide with important allocation of resources. In Spain they are performed within a theoretical job-specific health surveillance system. Our objective was to ascertain their occupational preventive usefulness from the perspective of occupational health professionals. Cross sectional study. Online survey addressed to all physicians and nurses members of the Catalan Society of Safety and Occupational Medicine (n=539) in 2011. Univariate and bivariate analyses of prevalence and prevalence differences of answers. Response rate 53% (n=285). According to more than 70% of respondents the health surveillance system isn't cost-effective, doesn't meet the goal of early detection of health damage related to work, and doesn't contribute to improve the occupational risk prevention system. Further deficiencies were identified regarding specificity and scientific basis for health examinations, quality of collective health surveillance and referral of suspected cases to mutual insurance companies for diagnosis and treatment. Bivariate analysis showed a significantly more negative opinion for several items amongst physicians (versus nurses) and amongst professionals working in external prevention services (versus internal services). This study raises serious concerns about how health examinations are performed within our workers' health surveillance system, which should be reviewed to ensure the fulfilment of its occupational preventive objective. Our results might encourage other countries with similar practices to assess them in order to assure their fitness for purpose. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  7. Occupational Mental Health, Labor Accidents and Occupational Diseases

    ERIC Educational Resources Information Center

    Naveillan, F. Pedro

    1973-01-01

    The article discusses the relationship between mental health and labor accidents as it pertains to accident prevention, treatment of accident victims, and their rehabilitation. It also comments briefly on mental health and occupational diseases and the scope of the field of occupational mental health from a Chilean perspective. (AG)

  8. Macrophage dysfunction initiates colitis during weaning of infant mice lacking the interleukin-10 receptor

    PubMed Central

    Redhu, Naresh S; Bakthavatchalu, Vasudevan; Conaway, Evan A; Shouval, Dror S; Tsou, Amy; Goettel, Jeremy A; Biswas, Amlan; Wang, Chuanwu; Field, Michael; Muller, Werner; Bleich, Andre; Li, Ning; Gerber, Georg K; Bry, Lynn; Fox, James G; Snapper, Scott B; Horwitz, Bruce H

    2017-01-01

    Infants with defects in the interleukin 10 receptor (IL10R) develop very early onset inflammatory bowel disease. Whether IL10R regulates lamina propria macrophage function during infant development in mice and whether macrophage-intrinsic IL10R signaling is required to prevent colitis in infancy is unknown. Here we show that although signs of colitis are absent in IL10R-deficient mice during the first two weeks of life, intestinal inflammation and macrophage dysfunction begin during the third week of life, concomitant with weaning and accompanying diversification of the intestinal microbiota. However, IL10R did not directly regulate the microbial ecology during infant development. Interestingly, macrophage depletion with clodronate inhibited the development of colitis, while the absence of IL10R specifically on macrophages sensitized infant mice to the development of colitis. These results indicate that IL10R-mediated regulation of macrophage function during the early postnatal period is indispensable for preventing the development of murine colitis. DOI: http://dx.doi.org/10.7554/eLife.27652.001 PMID:28678006

  9. Compound C inhibits macrophage chemotaxis through an AMPK-independent mechanism

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Youngyi; Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk 54896; Park, Byung-Hyun, E-mail: bhpark@jbnu.ac.kr

    Macrophage infiltration in adipose tissue is a well-established cause of obesity-linked insulin resistance. AMP-activated protein kinase (AMPK) activation in peripheral tissues such as adipose tissue has beneficial effects on the protection against obesity-induced insulin resistance, which is mainly mediated by prevention of adipose tissue macrophage infiltration and inflammation. In examining the role of AMPK on adipose tissue inflammation, we unexpectedly found that compound C (CC), despite its inhibition of AMPK, robustly inhibited macrophage chemotaxis in RAW 264.7 cells when adipocyte conditioned medium (CM) was used as a chemoattractant. Here, we report that CC inhibition of macrophage migration occurred independently ofmore » AMPK. Mechanistically, this inhibitory effect of cell migration by CC was mediated by inhibition of the focal adhesion kinase, AKT, nuclear factor κB pathways. Moreover, the expression of chemokine monocyte chemoattractant protein-1 and pro-inflammatory genes such as tumor necrosis factor α and inducible nitric oxide synthase were prevented by CC treatment in RAW 264.7 cells stimulated with either adipocyte CM or lipopolysaccharide. Lastly, in accord with the findings of the anti-inflammatory effect of CC, we demonstrated that CC functioned as a repressor of macrophage CM-mediated insulin resistance in adipocytes. Taken together, our results suggest that CC serves as a useful inhibitory molecule against macrophage chemotaxis into adipose tissue and thus might have therapeutic potential for the treatment of obesity-linked adipose inflammation. - Highlights: • Compound C (CC) inhibits macrophage chemotaxis regardless of AMPK suppression. • CC enhances insulin sensitivity in adipocytes. • CC inhibits focal adhesion kinase, AKT, and NF-κB signaling in RAW 264.7 cells.« less

  10. Myeloid hypoxia-inducible factor 1α prevents airway allergy in mice through macrophage-mediated immunoregulation.

    PubMed

    Toussaint, M; Fievez, L; Drion, P-V; Cataldo, D; Bureau, F; Lekeux, P; Desmet, C J

    2013-05-01

    Hypoxia-inducible factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1α in the myeloid lineage consequently results in decreased inflammatory responses in classical models of acute inflammation in mice. By contrast, we report here that mice conditionally deficient for Hif1α in myeloid cells display enhanced sensitivity to the development of airway allergy to experimental allergens and house-dust mite antigens. We support that upon allergen exposure, MyD88-dependent upregulation of Hif1α boosts the expression of the immunosuppressive cytokine interleukin (IL)-10 by lung interstitial macrophages (IMs). Hif1α-dependent IL-10 secretion is required for IMs to block allergen-induced dendritic cell activation and consequently for preventing the development of allergen-specific T-helper cell responses upon allergen exposure. Thus, this study supports that, in addition to its known pro-inflammatory activities, myeloid Hif1α possesses immunoregulatory functions implicated in the prevention of airway allergy.

  11. Staphylococcal enterotoxins bind H-2Db molecules on macrophages

    NASA Technical Reports Server (NTRS)

    Beharka, A. A.; Iandolo, J. J.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    We screened a panel of monoclonal antibodies against selected macrophage cell surface molecules for their ability to inhibit enterotoxin binding to major histocompatibility complex class II-negative C2D (H-2b) macrophages. Two monoclonal antibodies, HB36 and TIB126, that are specific for the alpha 2 domain of major histocompatibility complex class I, blocked staphylococcal enterotoxins A and B (SEA and SEB, respectively) binding to C2D macrophages in a specific and concentration-dependent manner. Inhibitory activities were haplotype-specific in that SEA and SEB binding to H-2k or H-2d macrophages was not inhibited by either monoclonal antibody. HB36, but not TIB126, inhibited enterotoxin-induced secretion of cytokines by H-2b macrophages. Lastly, passive protection of D-galactosamine-sensitized C2D mice by injection with HB36 antibody prevented SEB-induced death. Therefore, SEA and SEB binding to the alpha 2 domain of the H-2Db molecule induces biological activity and has physiological consequences.

  12. [Preventive care of pregnant employees. Is there a need to set rules of cooperation between occupational and gynecologist-obstetricians?].

    PubMed

    Marcinkiewicz, Andrzej; Hanke, Wojciech

    2012-01-01

    From 2008 the obstetric care for pregnancy-related conditions has been the most common cause of sickness absence. One of the postulated causes of frequent use of sick leaves by gravids is the fear of potential harmful and arduous factors in the workplace. An insufficient involvement of occupational health services in the implementation of actions aimed at protecting pregnant employees from risks to their health and safety in the work environment, imposed by Polish law, is also suggested. A survey on the current state of preventive care of pregnant employees was conducted among gynecologists-obstetricians working in the Lodz hospitals. They were asked to present their opinions in this regard. In the opinion of the surveyed gynecologists occupational physicians do not implement their tasks involving preventive care of pregnant employees, and the main burden of care lies with their gynecologists. They admitted that the decision to certify that a pregnant employee is temporarily unable to work is determined not only by the health assessment of a pregnant employee, but also by exposures and loads occurring in her workplace. They emphasized the lack of direct contacts between gynecologists and occupational physicians who should share the information on the potential impact of working conditions on the pregnant employee's health. The survey confirmed the need, noticed also by gynecologists to elaborate standards of specific preventive care addressed to pregnant employees and to set the rules of cooperation between occupational physicians and gynecologist-obstetricians.

  13. Effectiveness of interventions for preventing occupational irritant hand dermatitis: a quantitative systematic review protocol.

    PubMed

    Papadatou, Zoi; Cooper, Kay; Klein, Susan; MacDuff, Colin; Steiner, Markus

    2016-10-01

    The objective of this quantitative systematic review is to identify, appraise and synthesize the best available evidence on the effectiveness of moisturizers, barrier creams, protective gloves, skin protection education and complex interventions (a combination of two or more of the interventions listed) in preventing occupational irritant hand dermatitis (OIHD) in wet workers. These interventions will be compared to an alternative intervention or to usual care (workers regular skin care regime). The specific review question is: "What is the effectiveness of moisturizers, barrier creams, protective gloves, skin protection education and complex interventions in preventing OIHD in wet workers?"

  14. Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

    PubMed Central

    McDonald, Erin M.; Pilonieta, M. Carolina; Nick, Heidi J.

    2015-01-01

    During acute infection with bacteria, viruses or parasites, a fraction of macrophages engulf large numbers of red and white blood cells, a process called hemophagocytosis. Hemophagocytes persist into the chronic stage of infection and have an anti-inflammatory phenotype. Salmonella enterica serovar Typhimurium infection of immunocompetent mice results in acute followed by chronic infection, with the accumulation of hemophagocytes. The mechanism(s) that triggers a macrophage to become hemophagocytic is unknown, but it has been reported that the proinflammatory cytokine gamma interferon (IFN-γ) is responsible. We show that primary macrophages become hemophagocytic in the absence or presence of IFN-γ upon infection with Gram-negative bacterial pathogens or prolonged exposure to heat-killed Salmonella enterica, the Gram-positive bacterium Bacillus subtilis, or Mycobacterium marinum. Moreover, conserved microbe-associated molecular patterns are sufficient to stimulate macrophages to hemophagocytose. Purified bacterial lipopolysaccharide (LPS) induced hemophagocytosis in resting and IFN-γ-pretreated macrophages, whereas lipoteichoic acid and synthetic unmethylated deoxycytidine-deoxyguanosine dinucleotides, which mimic bacterial DNA, induced hemophagocytosis only in IFN-γ-pretreated macrophages. Chemical inhibition or genetic deletion of Toll-like receptor 4, a pattern recognition receptor responsive to LPS, prevented both Salmonella- and LPS-stimulated hemophagocytosis. Inhibition of NF-κB also prevented hemophagocytosis. These results indicate that recognition of microbial products by Toll-like receptors stimulates hemophagocytosis, a novel outcome of prolonged Toll-like receptor signaling, suggesting hemophagocytosis is a highly conserved innate immune response. PMID:26459510

  15. Prevention concept in industry: improvement in occupational safety and health protection--an empirical study.

    PubMed

    Ramsauer, F

    2001-12-01

    This prevention concept offers a contribution to the expansion of the set of instruments for occupational safety and health protection within workplace prevention. The concept involves the multilateral analysis of work conditions. The utilized instruments include a strategy group, a survey, a health issue round table, and an analysis of work demands, and lead to synergy effects at the results level. Employees are drawn into the analysis of work conditions and workplace design solutions for the improvement of the work situation. The prevention concept was tested in a large company and its application established in practice. It was accepted by all participants, and the comparison with the previous situation (defined only through the analysis of work demands) demonstrated a significant improvement in health protection.

  16. 77 FR 4048 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ... occupational safety and health services, and the prevention of work-related injury and illness. It is... the magnitude of the aggregate health burden associated with occupational injuries and illnesses, as... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health, (NIOSH) In...

  17. 76 FR 52330 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-22

    ... occupational safety and health services, and the prevention of work-related injury and illness. It is... the magnitude of the aggregate health burden associated with occupational injuries and illnesses, as... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH) In...

  18. 77 FR 51810 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-27

    ... occupational safety and health services, and the prevention of work-related injury and illness. It is... the magnitude of the aggregate health burden associated with occupational injuries and illnesses, as... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH) In...

  19. Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kinoshita, Hiroyuki; Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp; Ishii, Norio

    Highlights: ► We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ► Apocynin prevented atherosclerotic lesion formation. ► Apocynin suppressed ROS production in aorta and in macrophages. ► Apocynin suppressed cytokine expression and cell proliferation in macrophages. ► Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progressionmore » of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE{sup –/–}) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE{sup –/–} mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE{sup –/–} mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis.« less

  20. Macrophages largely contribute to heterologous anti-Propionibacterium acnes antibody-mediated protection from Actinobacillus pleuropneumoniae infection in mice.

    PubMed

    Ma, Qiuyue; Sun, Changjiang; Yang, Feng; Wang, Lei; Qin, Wanhai; Xia, Xiaojing; Feng, Xin; Du, Chongtao; Gu, Jingmin; Han, Wenyu; Lei, Liancheng

    2015-03-01

    Actinobacillus pleuropneumoniae is the causative agent of acute and chronic pleuropneumonia. Propionibacterium acnes is a facultative anaerobic gram-positive corynebacterium. We have previously found that anti-P. acnes antibodies can prevent A. pleuropneumoniae infections in mice. To investigate the role of macrophages in this process, affinity-purified anti-P. acnes IgG and anti-A. pleuropneumoniae IgG were used in opsonophagocytosis assays. Additionally, the efficacy of passive immunization with P. acnes serum against A. pleuropneumoniae was tested in macrophage-depleted mice. It was found that anti-P. acnes IgG had an effect similar to that of anti-A. pleuropneumoniae IgG (P > 0.05), which significantly promotes phagocytosis of A. pleuropneumoniae by macrophages (P < 0.01). It was also demonstrated that, after passive immunization with anti-P. acnes serum, macrophage-replete mice had the highest survival rate (90%), whereas the survival rate of macrophage-depleted mice was only 40% (P < 0.05). However, macrophage-depleted mice that had been passively immunized with naïve serum had the lowest survival rate (20%), this rate being lower than that of macrophage-replete mice that had been passively immunized with naïve serum. Overall, anti-P. acnes antibodies did not prevent A. pleuropneumoniae infection under conditions of macrophage depletion (P > 0.05). Furthermore, in mice that had been passively immunized with anti-P. acnes serum, macrophage depletion resulted in a greater A. pleuropneumoniae burden and more severe pathological features of pneumonia in lung tissues than occurred in macrophage-replete mice. It was concluded that macrophages are essential for the process by which anti-P. acnes antibody prevents A. pleuropneumoniae infection in mice. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  1. Protein Thiol Redox Signaling in Monocytes and Macrophages.

    PubMed

    Short, John D; Downs, Kevin; Tavakoli, Sina; Asmis, Reto

    2016-11-20

    Monocyte and macrophage dysfunction plays a critical role in a wide range of inflammatory disease processes, including obesity, impaired wound healing diabetic complications, and atherosclerosis. Emerging evidence suggests that the earliest events in monocyte or macrophage dysregulation include elevated reactive oxygen species production, thiol modifications, and disruption of redox-sensitive signaling pathways. This review focuses on the current state of research in thiol redox signaling in monocytes and macrophages, including (i) the molecular mechanisms by which reversible protein-S-glutathionylation occurs, (ii) the identification of bona fide S-glutathionylated proteins that occur under physiological conditions, and (iii) how disruptions of thiol redox signaling affect monocyte and macrophage functions and contribute to atherosclerosis. Recent Advances: Recent advances in redox biochemistry and biology as well as redox proteomic techniques have led to the identification of many new thiol redox-regulated proteins and pathways. In addition, major advances have been made in expanding the list of S-glutathionylated proteins and assessing the role that protein-S-glutathionylation and S-glutathionylation-regulating enzymes play in monocyte and macrophage functions, including monocyte transmigration, macrophage polarization, foam cell formation, and macrophage cell death. Protein-S-glutathionylation/deglutathionylation in monocytes and macrophages has emerged as a new and important signaling paradigm, which provides a molecular basis for the well-established relationship between metabolic disorders, oxidative stress, and cardiovascular diseases. The identification of specific S-glutathionylated proteins as well as the mechanisms that control this post-translational protein modification in monocytes and macrophages will facilitate the development of new preventive and therapeutic strategies to combat atherosclerosis and other metabolic diseases. Antioxid. Redox Signal

  2. Occupational rhinitis.

    PubMed

    Petrick, Maria M; Slavin, Raymond G

    2003-05-01

    This article aims to define occupational rhinitis, classify its various causes, review the steps in its diagnosis, and describe its nonpharmacologic and pharmacologic principles of management. Occupational rhinitis frequently coexists with asthma but also occurs alone. Although it does not have the same impact as occupational asthma, occupational rhinitis causes distress, discomfort, and work inefficiency. By concentrating on the patient's workplace, the clinician has an opportunity to practice preventive medicine: to recognize substances in the patient's micro- and macroenvironment that are causing the problems and then to intervene by altering the environment or removing the patient from the environment.

  3. Innovation in the occupational health physician profession requires the development of a work collective to improve the efficiency of MSD prevention.

    PubMed

    Caroly, S; Landry, A; Cholez, C; Davezies, P; Bellemare, M; Poussin, N

    2012-01-01

    Given the ageing population of occupational health physicians and the deteriorating situation of employee health, reforms targeting the multi-disciplinary nature of occupational health are currently being drawn up. These are of great concern to doctors in terms of the future of occupational health, notably with regard to changing medical practices. The objective of this study is to explore the actual practices of occupational health physicians within the framework of MSD prevention in France. By analysing the activity of occupational health physicians, we could gain a better understanding of the coordination between those involved in OHS with the ultimate goal being to improve prevention. Based on an analysis of peer activity, this method made it possible to push beyond pre-constructed discourse. According to activity theories, it is through others that the history and controversies of a profession can be grasped and skills developed. The results produced by these collective discussions on activity analysis contributed to establish a collective point of view about the important aspects of their profession that need defending and the variations in professional genre in relation to the current reforms, notably.

  4. 78 FR 56235 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-12

    ... delivery of occupational safety and health services, and the prevention of work-related injury and illness... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH or... occupational safety and health, and allied areas. It is the intent of NIOSH to support broad-based research...

  5. 78 FR 24751 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-26

    ... improvements in the delivery of occupational safety and health services, and the prevention of work-related... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH or... issues in occupational safety and health, and allied areas. It is the intent of NIOSH to support broad...

  6. An M1-like Macrophage Polarization in Decidual Tissue during Spontaneous Preterm Labor That Is Attenuated by Rosiglitazone Treatment.

    PubMed

    Xu, Yi; Romero, Roberto; Miller, Derek; Kadam, Leena; Mial, Tara N; Plazyo, Olesya; Garcia-Flores, Valeria; Hassan, Sonia S; Xu, Zhonghui; Tarca, Adi L; Drewlo, Sascha; Gomez-Lopez, Nardhy

    2016-03-15

    Decidual macrophages are implicated in the local inflammatory response that accompanies spontaneous preterm labor/birth; however, their role is poorly understood. We hypothesized that decidual macrophages undergo a proinflammatory (M1) polarization during spontaneous preterm labor and that PPARγ activation via rosiglitazone (RSG) would attenuate the macrophage-mediated inflammatory response, preventing preterm birth. In this study, we show that: 1) decidual macrophages undergo an M1-like polarization during spontaneous term and preterm labor; 2) anti-inflammatory (M2)-like macrophages are more abundant than M1-like macrophages in decidual tissue; 3) decidual M2-like macrophages are reduced in preterm pregnancies compared with term pregnancies, regardless of the presence of labor; 4) decidual macrophages express high levels of TNF and IL-12 but low levels of peroxisome proliferator-activated receptor γ (PPARγ) during spontaneous preterm labor; 5) decidual macrophages from women who underwent spontaneous preterm labor display plasticity by M1↔M2 polarization in vitro; 6) incubation with RSG reduces the expression of TNF and IL-12 in decidual macrophages from women who underwent spontaneous preterm labor; and 7) treatment with RSG reduces the rate of LPS-induced preterm birth and improves neonatal outcomes by reducing the systemic proinflammatory response and downregulating mRNA and protein expression of NF-κB, TNF, and IL-10 in decidual and myometrial macrophages in C57BL/6J mice. In summary, we demonstrated that decidual M1-like macrophages are associated with spontaneous preterm labor and that PPARγ activation via RSG can attenuate the macrophage-mediated proinflammatory response, preventing preterm birth and improving neonatal outcomes. These findings suggest that the PPARγ pathway is a new molecular target for future preventative strategies for spontaneous preterm labor/birth. Copyright © 2016 by The American Association of Immunologists, Inc.

  7. [Occupational cancer].

    PubMed

    Mori, Ippei

    2014-02-01

    Occupational cancer is one of the most important topics in occupational health, because it can be avoided by using appropriate risk management strategies at work. However, due to the lack of suitable surveillance systems in Japan, it goes under-recognized. Burden of disease studies conducted elsewhere can be extrapolated to suggest thousands of deaths are attributable to occupational cancer in Japan. By law, about 20 kinds of cancer have been listed as occupational hazards; among those is asbestos related cancer. In fact, in recent years, thousands of asbestos related cancer cases have been compensated by the government run workers' compensation scheme for occupational accidents and diseases. On the other hand, for the other types of occupational cancer, only few cases are reported. To prevent re-emergence of occupational cancer, such as the recently publicized cholangiocarcinoma epidemics, employees, employers, medical institutions and competent authorities are strongly urged to establish better surveillance systems for occupational cancer.

  8. An M1-like macrophage polarization in decidual tissue during spontaneous preterm labor that is attenuated by rosiglitazone treatment1

    PubMed Central

    Kadam, Leena; Mial, Tara N.; Plazyo, Olesya; Garcia-Flores, Valeria; Hassan, Sonia S.; Xu, Zhonghui; Tarca, Adi L.; Drewlo, Sascha; Gomez-Lopez, Nardhy

    2016-01-01

    Macrophages are implicated in the local inflammatory response that accompanies spontaneous preterm labor/birth; however, their role is poorly understood. We hypothesized that decidual macrophages undergo an M1 polarization during spontaneous preterm labor and that PPARγ activation via rosiglitazone would attenuate the macrophage-mediated inflammatory response, preventing preterm birth. Herein, we show that: 1) decidual macrophages undergo an M1-like polarization during spontaneous term and preterm labor; 2) M2-like macrophages are more abundant than M1-like macrophages in decidual tissue; 3) decidual M2-like macrophages are reduced in preterm pregnancies compared to term pregnancies, regardless of the presence of labor; 4) decidual macrophages express high levels of TNF and IL12, but low levels of PPARγ, during spontaneous preterm labor; 5) decidual macrophages from women who underwent spontaneous preterm labor display plasticity by M1↔M2 polarization in vitro; 6) incubation with rosiglitazone reduces the expression of TNF and IL12 in decidual macrophages from women who underwent spontaneous preterm labor; and 7) treatment with rosiglitazone reduces the rate of LPS-induced preterm birth and improves neonatal outcomes by reducing the systemic pro-inflammatory response in B6 mice and down-regulating mRNA and protein expression of NFκB, TNF, and IL10 in decidual and myometrial macrophages. In summary, we demonstrated that decidual M1-like macrophages are associated with spontaneous preterm labor, and that PPARγ activation via rosiglitazone can attenuate the macrophage-mediated pro-inflammatory response, preventing preterm birth and improving neonatal outcomes. These findings suggest that the PPARγ pathway is a new molecular target for future preventative strategies for spontaneous preterm labor/birth. PMID:26889045

  9. Unsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages[S

    PubMed Central

    L'homme, Laurent; Esser, Nathalie; Riva, Laura; Scheen, André; Paquot, Nicolas; Piette, Jacques; Legrand-Poels, Sylvie

    2013-01-01

    The NLRP3 inflammasome is involved in many obesity-associated diseases, such as type 2 diabetes, atherosclerosis, and gouty arthritis, through its ability to induce interleukin (IL)-1β release. The molecular link between obesity and inflammasome activation is still unclear, but free fatty acids have been proposed as one triggering event. Here we reported opposite effects of saturated fatty acids (SFAs) compared with unsaturated fatty acids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway. Unlike SFAs, the UFAs oleate and linoleate did not lead to IL-1β secretion. In addition, they totally prevented the IL-1β release induced by SFAs and, with less efficiency, by a broad range of NLRP3 inducers, including nigericin, alum, and monosodium urate. UFAs did not affect the transcriptional effect of SFAs, suggesting a specific effect on the NLRP3 activation. These results provide a new anti-inflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and, therefore, IL-1β processing. By this way, UFAs might play a protective role in NLRP3-associated diseases. PMID:24006511

  10. Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy

    PubMed Central

    Crittenden, Marka R.; Baird, Jason; Friedman, David; Savage, Talicia; Uhde, Lauren; Alice, Alejandro; Cottam, Benjamin; Young, Kristina; Newell, Pippa; Nguyen, Cynthia; Bambina, Shelly; Kramer, Gwen; Akporiaye, Emmanuel; Malecka, Anna; Jackson, Andrew; Gough, Michael J.

    2016-01-01

    Radiation therapy provides a means to kill large numbers of cancer cells in a controlled location resulting in the release of tumor-specific antigens and endogenous adjuvants. However, by activating pathways involved in apoptotic cell recognition and phagocytosis, irradiated cancer cells engender suppressive phenotypes in macrophages. We demonstrate that the macrophage-specific phagocytic receptor, Mertk is upregulated in macrophages in the tumor following radiation therapy. Ligation of Mertk on macrophages results in anti-inflammatory cytokine responses via NF-kB p50 upregulation, which in turn limits tumor control following radiation therapy. We demonstrate that in immunogenic tumors, loss of Mertk is sufficient to permit tumor cure following radiation therapy. However, in poorly immunogenic tumors, TGFb inhibition is also required to result in tumor cure following radiation therapy. These data demonstrate that Mertk is a highly specific target whose absence permits tumor control in combination with radiation therapy. PMID:27602953

  11. Macrophage Apoptosis and Efferocytosis in the Pathogenesis of Atherosclerosis

    PubMed Central

    Linton, MacRae F.; Babaev, Vladimir R.; Huang, Jiansheng; Linton, Edward F.; Tao, Huan; Yancey, Patricia G.

    2017-01-01

    Macrophage apoptosis and the ability of macrophages to clean up dead cells, a process called efferocytosis, are crucial determinants of atherosclerosis lesion progression and plaque stability. Environmental stressors initiate endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR). Unresolved ER stress with activation of the UPR initiates apoptosis. Macrophages are resistant to apoptotic stimuli, because of activity of the PI3K/Akt pathway. Macrophages express 3 Akt isoforms, Akt1, Akt2 and Akt3, which are products of distinct but homologous genes. Akt displays isoform-specific effects on atherogenesis, which vary with different vascular cell types. Loss of macrophage Akt2 promotes the anti-inflammatory M2 phenotype and reduces atherosclerosis. However, Akt isoforms are redundant with regard to apoptosis. c-Jun NH2-terminal kinase (JNK) is a pro-apoptotic effector of the UPR, and the JNK1 isoform opposes anti-apoptotic Akt signaling. Loss of JNK1 in hematopoietic cells protects macrophages from apoptosis and accelerates early atherosclerosis. IκB kinase α (IKKα, a member of the serine/threonine protein kinase family) plays an important role in mTORC2-mediated Akt signaling in macrophages, and IKKα deficiency reduces macrophage survival and suppresses early atherosclerosis. Efferocytosis involves the interaction of receptors, bridging molecules, and apoptotic cell ligands. Scavenger receptor class B type I is a critical mediator of macrophage efferocytosis via the Src/PI3K/Rac1 pathway in atherosclerosis. Agonists that resolve inflammation offer promising therapeutic potential to promote efferocytosis and prevent atherosclerotic clinical events. PMID:27725526

  12. Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages.

    PubMed

    Jin, Xueting; Kruth, Howard S

    2016-06-30

    A protocol is presented for cell culture of macrophage colony-stimulating factor (M-CSF) differentiated human monocyte-derived macrophages. For initiation of experiments, fresh or frozen monocytes are cultured in flasks for 1 week with M-CSF to induce their differentiation into macrophages. Then, the macrophages can be harvested and seeded into culture wells at required cell densities for carrying out experiments. The use of defined numbers of macrophages rather than defined numbers of monocytes to initiate macrophage cultures for experiments yields macrophage cultures in which the desired cell density can be more consistently attained. Use of cryopreserved monocytes reduces dependency on donor availability and produces more homogeneous macrophage cultures.

  13. Impaired plasticity of macrophages in X-linked adrenoleukodystrophy.

    PubMed

    Weinhofer, Isabelle; Zierfuss, Bettina; Hametner, Simon; Wagner, Magdalena; Popitsch, Niko; Machacek, Christian; Bartolini, Barbara; Zlabinger, Gerhard; Ohradanova-Repic, Anna; Stockinger, Hannes; Köhler, Wolfgang; Höftberger, Romana; Regelsberger, Günther; Forss-Petter, Sonja; Lassmann, Hans; Berger, Johannes

    2018-05-30

    , thus possibly contributing to the devastating rapidly progressive demyelination in cerebral adrenoleukodystrophy that only in rare cases arrests spontaneously. These findings emphasize monocytes/macrophages as crucial therapeutic targets for preventing or stopping myelin destruction in patients with X-linked adrenoleukodystrophy.

  14. Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell invasion

    PubMed Central

    Rietkötter, Eva; Menck, Kerstin; Bleckmann, Annalen; Farhat, Katja; Schaffrinski, Meike; Schulz, Matthias; Hanisch, Uwe-Karsten; Binder, Claudia; Pukrop, Tobias

    2013-01-01

    The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether this is due to direct toxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ metastasis and could be a crucial target of ZA. Thus, we comparatively investigate the ZA effects on: i) different types of macrophages, ii) on breast cancer cells but also iii) on macrophage-induced invasion. We demonstrate that ZA concentrations reflecting the plasma level affected viability of human macrophages, murine bone marrow-derived macrophages as well as their resident brain equivalents, the microglia, while it did not influence the tested cancer cells. However, the effects on the macrophages subsequently reduced the macrophage/microglia-induced invasiveness of the cancer cells. In line with this, manipulation of microglia by ZA in organotypic brain slice cocultures reduced the tissue invasion by carcinoma cells. The characterization of human macrophages after ZA treatment revealed a phenotype/response shift, in particular after external stimulation. In conclusion, we show that therapeutic concentrations of ZA affect all types of macrophages but not the cancer cells. Thus, anti-metastatic effects of ZA are predominantly caused by modulating the microenvironment. Most importantly, our findings demonstrate that ZA reduced microglia-assisted invasion of cancer cells to the brain tissue, indicating a potential therapeutic role in the prevention of cerebral metastasis. PMID:24036536

  15. Brucella infection inhibits macrophages apoptosis via Nedd4-dependent degradation of calpain2.

    PubMed

    Cui, Guimei; Wei, Pan; Zhao, Yuxi; Guan, Zhenhong; Yang, Li; Sun, Wanchun; Wang, Shuangxi; Peng, Qisheng

    2014-11-07

    The calcium-dependent protease calpain2 is involved in macrophages apoptosis. Brucella infection-induced up-regulation of intracellular calcium level is an essential factor for the intracellular survival of Brucella within macrophages. Here, we hypothesize that calcium-dependent E3 ubiquitin ligase Nedd4 ubiquitinates calpain2 and inhibits Brucella infection-induced macrophage apoptosis via degradation of calpain2.Our results reveal that Brucella infection induces increases in Nedd4 activity in an intracellular calcium dependent manner. Furthermore, Brucella infection-induced degradation of calpain2 is mediated by Nedd4 ubiquitination of calpain2. Brucella infection-induced calpain2 degradation inhibited macrophages apoptosis. Treatment of Brucella infected macrophages with calcium chelator BAPTA or Nedd4 knock-down decreased Nedd4 activity, prevented calpain2 degradation, and resulted in macrophages apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Occupational asthma prevention and management in industry--an example of a global programme.

    PubMed

    Gannon, Paul F G; Berg, A S; Gayosso, R; Henderson, B; Sax, S E; Willems, H M J

    2005-12-01

    Isocyanates are widely used in the manufacture of polyurethane foams, plastics, coatings and adhesives, and are known to cause occupational asthma in a proportion of exposed workers. Substitution as a prevention strategy is not currently a feasible option. For this reason, health and safety professionals working together in an automotive coatings business created a proactive global programme to address the known potential effects of isocyanates on its workers. The goals of the programme are prevention, early detection and mitigation of effect of key endpoints, especially asthma and to a lesser degree dermatitis, in people who are occupationally exposed, or potentially exposed, to isocyanates and products containing isocyanates. The surveillance programme for isocyanates has several important components, which include assessment of exposure, pre-placement questionnaire and spirometry, training and education of employees, regularly administered periodic questionnaires, medical assessment for abnormal questionnaire responses, process for early reporting and investigation of symptomatic employees and incidents, group data review and management reporting. Although regional differences exist regarding availability of specialized services, we have successfully implemented this programme in parts of North America, Europe and Latin America, and are currently implementing elsewhere. These simple control measures are relatively inexpensive and can be applied in even small business settings. It is recommended that all employers who manufacture, handle or use isocyanate-containing products consider such a strategy.

  17. Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages.

    PubMed

    Jia, Xiao-Hua; Du, Yang; Mao, Duo; Wang, Zhong-Liang; He, Zhen-Qiang; Qiu, Jing-Dan; Ma, Xi-Bo; Shang, Wen-Ting; Ding, Dan; Tian, Jie

    2015-09-22

    Zoledronic acid (ZA) has been tested in clinical trials as an additive therapy for early-stage breast cancer. However, the mechanism by which ZA exerts its antitumor activity is still unclear. The aim of this study is to investigate whether the prevention of tumor growth by ZA is through regulating the mesenchymal stem cells (MSC)-monocyte chemotactic protein 1 (MCP-1)-macrophages axis in the tumor microenvironment. To address this issue, MDA-MB-231-FLUC human breast cancer cells were cultured and injected either alone, or coupled with MSC into the mammary fat pads of nude mice. MSC were treated with either ZA or untreated. Tumor growth was determined by using an in vivo bioluminescence imaging (BLI) and the tumor-associated macrophages (TAMs) in tumor tissues were immunohistochemically analyzed by using CD206 antibody. The effects of ZA on the cytokine related gene expression of MSC were assessed by using real-time PCR. In this study, we found that ZA-treated mice showed a significant delay in tumor growth. In addition, our data revealed that ZA weakened the ability of MSC to promote tumor growth by impairing TAMs recruitment and tumor vascularization. Furthermore, it was found that ZA decreased MCP-1 expression of MSC, and therefore reduced the recruitment of TAMs to the tumor sites and hence inhibited the tumor growth. Altogether, our study demonstrated ZA can prevent the tumor-promoting effects of MSC. The antitumor effects of ZA were caused by decreasing the MCP-1 expression of MSC, which further decreased the infiltration of TAMs into tumor sites, and therefore inhibited the tumor growth.

  18. Macrophage Activation Mechanisms in Human Monocytic Cell Line-derived Macrophages.

    PubMed

    Sumiya, Yu; Ishikawa, Mami; Inoue, Takahiro; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

    2015-08-01

    Although the mechanisms of macrophage activation are important for cancer immunotherapy, they are poorly understood. Recently, easy and robust assay systems for assessing the macrophage-activating factor (MAF) using monocytic cell line-derived macrophages were established. Gene-expression profiles of U937- and THP-1-derived macrophages were compared using gene expression microarray analysis and their responses against several MAFs were examined by in vitro experiments. Activated states of these macrophages could not be assigned to a specific sub-type but showed, however, different unique characteristics. The unique of monocytic cell line-derived macrophages could provide clues to understand the activation mechanism of macrophages and, therefore, help to develop effective cancer immunotherapy with MAFs. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Diplomatic Assistance: Can Helminth-Modulated Macrophages Act as Treatment for Inflammatory Disease?

    PubMed Central

    Steinfelder, Svenja; O’Regan, Noëlle Louise; Hartmann, Susanne

    2016-01-01

    Helminths have evolved numerous pathways to prevent their expulsion or elimination from the host to ensure long-term survival. During infection, they target numerous host cells, including macrophages, to induce an alternatively activated phenotype, which aids elimination of infection, tissue repair, and wound healing. Multiple animal-based studies have demonstrated a significant reduction or complete reversal of disease by helminth infection, treatment with helminth products, or helminth-modulated macrophages in models of allergy, autoimmunity, and sepsis. Experimental studies of macrophage and helminth therapies are being translated into clinical benefits for patients undergoing transplantation and those with multiple sclerosis. Thus, helminths or helminth-modulated macrophages present great possibilities as therapeutic applications for inflammatory diseases in humans. Macrophage-based helminth therapies and the underlying mechanisms of their therapeutic or curative effects represent an under-researched area with the potential to open new avenues of treatment. This review explores the application of helminth-modulated macrophages as a new therapy for inflammatory diseases. PMID:27101372

  20. Inflammation induced mTORC2-Akt-mTORC1 signaling promotes macrophage foam cell formation.

    PubMed

    Banerjee, Dipanjan; Sinha, Archana; Saikia, Sudeshna; Gogoi, Bhaskarjyoti; Rathore, Arvind K; Das, Anindhya Sundar; Pal, Durba; Buragohain, Alak K; Dasgupta, Suman

    2018-06-05

    The transformation of macrophages into lipid loaded foam cells is a critical and early event in the pathogenesis of atherosclerosis. Several recent reports highlighted that induction of TLR4 signaling promotes macrophage foam cell formation; however, the underlying molecular mechanisms have not been clearly elucidated. Here, we found that the TLR4 mediated inflammatory signaling communicated with mTORC2-Akt-mTORC1 metabolic cascade in macrophage and thereby promoting lipid uptake and foam cell formation. Mechanistically, LPS treatment markedly upregulates TLR4 mediated inflammatory pathway which by activating mTORC2 induces Akt phosphorylation at serine 473 and that aggravate mTORC1 dependent scavenger receptors expression and consequent lipid accumulation in THP-1 macrophages. Inhibition of mTORC2 either by silencing Rictor expression or inhibiting its association with mTOR notably prevents LPS induced Akt activation, scavenger receptors expression and macrophage lipid accumulation. Although suppression of mTORC1 expression by genetic knockdown of Raptor did not produce any significant change in Akt S473 phosphorylation, however, incubation with Akt activator in Rictor silenced cells failed to promote scavenger receptors expression and macrophage foam cell formation. Thus, present research explored the signaling pathway involved in inflammation induced macrophage foam cells formation and therefore, targeting this pathway might be useful for preventing macrophage foam cell formation. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  1. 75 FR 5333 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-02

    ... aggregate health burden associated with occupational injuries and illnesses, as well as to support more... health services, and the prevention of work-related injury and illness. It is anticipated that research... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH) In...

  2. 76 FR 3908 - Safety and Occupational Health Study Section (SOHSS); National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-21

    ... the aggregate health burden associated with occupational injuries and illnesses, as well as to support... and health services, and the prevention of work-related injury and illness. It is anticipated that... Occupational Health Study Section (SOHSS); National Institute for Occupational Safety and Health (NIOSH...

  3. Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory.

    PubMed

    Iwanowycz, Stephen; Wang, Junfeng; Altomare, Diego; Hui, Yvonne; Fan, Daping

    2016-05-27

    Macrophages are pleiotropic cells capable of performing a broad spectrum of functions. Macrophage phenotypes are classified along a continuum between the extremes of proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. The seemingly opposing functions of M1 and M2 macrophages must be tightly regulated for an effective and proper response to foreign molecules or damaged tissue. Excessive activation of either M1 or M2 macrophages contributes to the pathology of many diseases. Emodin is a Chinese herb-derived compound and has shown potential to inhibit inflammation in various settings. In this study, we tested the ability of emodin to modulate the macrophage response to both M1 and M2 stimuli. Primary mouse macrophages were stimulated with LPS/IFNγ or IL4 with or without emodin, and the effects of emodin on gene transcription, cell signaling pathways, and histone modifications were examined by a variety of approaches, including microarray, quantitative real-time PCR, Western blotting, chromatin immunoprecipitation, and functional assays. We found that emodin bidirectionally tunes the induction of LPS/IFNγ- and IL4-responsive genes through inhibiting NFκB/IRF5/STAT1 signaling and IRF4/STAT6 signaling, respectively. Thereby, emodin modulates macrophage phagocytosis, migration, and NO production. Furthermore, emodin inhibited the removal of H3K27 trimethylation (H3K27m3) marks and the addition of H3K27 acetylation (H3K27ac) marks on genes required for M1 or M2 polarization of macrophages. In conclusion, our data suggest that emodin is uniquely able to suppress the excessive response of macrophages to both M1 and M2 stimuli and therefore has the potential to restore macrophage homeostasis in various pathologies. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory*

    PubMed Central

    Iwanowycz, Stephen; Wang, Junfeng; Altomare, Diego; Hui, Yvonne; Fan, Daping

    2016-01-01

    Macrophages are pleiotropic cells capable of performing a broad spectrum of functions. Macrophage phenotypes are classified along a continuum between the extremes of proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. The seemingly opposing functions of M1 and M2 macrophages must be tightly regulated for an effective and proper response to foreign molecules or damaged tissue. Excessive activation of either M1 or M2 macrophages contributes to the pathology of many diseases. Emodin is a Chinese herb-derived compound and has shown potential to inhibit inflammation in various settings. In this study, we tested the ability of emodin to modulate the macrophage response to both M1 and M2 stimuli. Primary mouse macrophages were stimulated with LPS/IFNγ or IL4 with or without emodin, and the effects of emodin on gene transcription, cell signaling pathways, and histone modifications were examined by a variety of approaches, including microarray, quantitative real-time PCR, Western blotting, chromatin immunoprecipitation, and functional assays. We found that emodin bidirectionally tunes the induction of LPS/IFNγ- and IL4-responsive genes through inhibiting NFκB/IRF5/STAT1 signaling and IRF4/STAT6 signaling, respectively. Thereby, emodin modulates macrophage phagocytosis, migration, and NO production. Furthermore, emodin inhibited the removal of H3K27 trimethylation (H3K27m3) marks and the addition of H3K27 acetylation (H3K27ac) marks on genes required for M1 or M2 polarization of macrophages. In conclusion, our data suggest that emodin is uniquely able to suppress the excessive response of macrophages to both M1 and M2 stimuli and therefore has the potential to restore macrophage homeostasis in various pathologies. PMID:27008857

  5. Occupational hazards to health of port workers.

    PubMed

    Wang, Yukun; Zhan, Shuifen; Liu, Yan; Li, Yan

    2017-12-01

    The aim of this article is to reduce the risk of occupational hazards and improve safety conditions by enhancing hazard knowledge and identification as well as improving safety behavior for freight port enterprises. In the article, occupational hazards to health and their prevention measures of freight port enterprises have been summarized through a lot of occupational health evaluation work, experience and understanding. Workers of freight port enterprises confront an equally wide variety of chemical, physical and psychological hazards in production technology, production environment and the course of labor. Such health hazards have been identified, the risks evaluated, the dangers to health notified and effective prevention measures which should be put in place to ensure the health of the port workers summarized. There is still a long way to go for the freight port enterprises to prevent and control the occupational hazards. Except for occupational hazards and their prevention measures, other factors that influence the health of port workers should also be paid attention to, such as age, work history, gender, contraindication and even the occurrence and development rules of occupational hazards in current production conditions.

  6. [Role of the occupational health nurse].

    PubMed

    Rauch, Nadine

    2018-02-01

    The missions of occupational health nurses are exclusively preventive, except in the event of emergency situations. They are involved in the prevention of occupational stress, the assessment of psychosocial risks and the improvement of quality of life at work. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Occupational hazards to hospital personnel

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Patterson, W.B.; Craven, D.E.; Schwartz, D.A.

    1985-05-01

    Hospital personnel are subject to various occupational hazards. Awareness of these risks, compliance with basic preventive measures, and adequate resources for interventions are essential components of an occupational health program. Physical, chemical, and radiation hazards; important infectious risks; and psychosocial problems prevalent in hospital workers are reviewed. A rational approach to managing and preventing these problems is offered. 370 references.

  8. Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees.

    PubMed

    Verweij, Lisanne M; Proper, Karin I; Weel, Andre N H; Hulshof, Carel T J; van Mechelen, Willem

    2009-12-14

    Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees. Following the guideline development protocol of the Netherlands Society of Occupational Medicine and the Intervention Mapping protocol, the guideline was developed based on literature, interviews with relevant stakeholders, and consensus among an expert group. The guideline consists of an individual and an environmental component. The individual component includes recommendations for occupational physicians on how to promote physical activity and healthy dietary behavior based on principles of motivational interviewing. The environmental component contains an obesogenic environment assessment tool. The guideline is evaluated in a randomised controlled trial among 20 occupational physicians. Occupational physicians in the intervention group apply the guideline to eligible workers during 6 months. Occupational physicians in the control group provide care as usual. Measurements take place at baseline and 6, 12, and 18 months thereafter. Primary outcome measures include waist circumference, daily physical activity and dietary behavior. Secondary outcome measures include sedentary behavior, determinants of behavior change, body weight and body mass index, cardiovascular disease risk profile, and quality of life. Additionally, productivity, absenteeism, and cost-effectiveness are assessed. Improving workers' daily physical activity and dietary behavior may prevent weight gain and subsequently improve workers' health, increase productivity, and reduce absenteeism. After an effect- and process evaluation the guideline will be

  9. Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

    PubMed Central

    2009-01-01

    Background Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees. Methods Following the guideline development protocol of the Netherlands Society of Occupational Medicine and the Intervention Mapping protocol, the guideline was developed based on literature, interviews with relevant stakeholders, and consensus among an expert group. The guideline consists of an individual and an environmental component. The individual component includes recommendations for occupational physicians on how to promote physical activity and healthy dietary behavior based on principles of motivational interviewing. The environmental component contains an obesogenic environment assessment tool. The guideline is evaluated in a randomised controlled trial among 20 occupational physicians. Occupational physicians in the intervention group apply the guideline to eligible workers during 6 months. Occupational physicians in the control group provide care as usual. Measurements take place at baseline and 6, 12, and 18 months thereafter. Primary outcome measures include waist circumference, daily physical activity and dietary behavior. Secondary outcome measures include sedentary behavior, determinants of behavior change, body weight and body mass index, cardiovascular disease risk profile, and quality of life. Additionally, productivity, absenteeism, and cost-effectiveness are assessed. Discussion Improving workers' daily physical activity and dietary behavior may prevent weight gain and subsequently improve workers' health, increase productivity, and reduce absenteeism. After an effect- and process

  10. Civilian law: from occupational medicine to occupational event.

    PubMed

    Mpotos, N; Watelet, J B

    Civilian law:from occupational medicine to occupational event. Despite the growing importance of objective measurements, the health effects of many occupational risk factors are currently not fully quantified. Occupational noise, as a widespread risk factor, is illustrative in this regard; there is a strong body of evidence linking it to an important health outcome (hearing loss), but it is less decisively associated with others (such as psychological disorders). It is also distinct from environmental noise, and therefore falls under the responsibility of employers as well as individuals. Noise-induced hearing loss (NIHL) is, at present, incurable and irreversible. However, it is preventable, if effective and global hearing conservation programmes can be implemented. These programmes should not be isolated efforts, but should be integrated into the overall hazard prevention and control programme of the workplace. Belgian law encompasses a set of provisions for prevention and the protection of the health and safety of workers within the workplace, including aspects pertaining to the hygiene of the workplace and psychosocial aspects at work (stress, violence, bullying and sexual harassment, among others). In principle, combating environmental noise is fully addressed in this country. However, other levels of policy-making also play an important role in this regard. For example, the federal government is in charge of product standards, and therefore also of noise emission standards for products. The interpretation and enforcement of Belgian legislation on well-being at work converts European directives and international agreements on well-being at work into Belgian law.

  11. 77 FR 27776 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... safety and health services, and the prevention of work-related injury and illness. It is anticipated that... magnitude of the aggregate health burden associated with occupational injuries and illnesses, as well as to... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH) In...

  12. 76 FR 18220 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-01

    ... safety and health services, and the prevention of work-related injury and illness. It is anticipated that... magnitude of the aggregate health burden associated with occupational injuries and illnesses, as well as to... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH) In...

  13. Current and new challenges in occupational lung diseases.

    PubMed

    De Matteis, Sara; Heederik, Dick; Burdorf, Alex; Colosio, Claudio; Cullinan, Paul; Henneberger, Paul K; Olsson, Ann; Raynal, Anne; Rooijackers, Jos; Santonen, Tiina; Sastre, Joaquin; Schlünssen, Vivi; van Tongeren, Martie; Sigsgaard, Torben

    2017-12-31

    Occupational lung diseases are an important public health issue and are avoidable through preventive interventions in the workplace. Up-to-date knowledge about changes in exposure to occupational hazards as a result of technological and industrial developments is essential to the design and implementation of efficient and effective workplace preventive measures. New occupational agents with unknown respiratory health effects are constantly introduced to the market and require periodic health surveillance among exposed workers to detect early signs of adverse respiratory effects. In addition, the ageing workforce, many of whom have pre-existing respiratory conditions, poses new challenges in terms of the diagnosis and management of occupational lung diseases. Primary preventive interventions aimed to reduce exposure levels in the workplace remain pivotal for elimination of the occupational lung disease burden. To achieve this goal there is still a clear need for setting standard occupational exposure limits based on transparent evidence-based methodology, in particular for carcinogens and sensitising agents that expose large working populations to risk. The present overview, focused on the occupational lung disease burden in Europe, proposes directions for all parties involved in the prevention of occupational lung disease, from researchers and occupational and respiratory health professionals to workers and employers. The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2017.

  14. Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohara, Kazuaki, E-mail: Kazuaki_Ohara@kirin.co.jp; Wakabayashi, Hideyuki; Taniguchi, Yoshimasa

    Highlights: •The major circulating quercetin metabolite (Q3GA) activated LXRα. •Q3GA induced ABCA1 via LXRα activation in macrophages. •Nelumbo nucifera leaf extracts contained quercetin glycosides. •N. nucifera leaf extract feeding elevated HDLC in mice. -- Abstract: Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found thatmore » quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.« less

  15. Tauroursodeoxycholic Acid Attenuates Lipid Accumulation in Endoplasmic Reticulum-Stressed Macrophages

    PubMed Central

    Hua, Yinan; Kandadi, Machender R.; Zhu, Meijun; Ren, Jun; Sreejayan, Nair

    2011-01-01

    Background/Aim Recent evidence suggests that endoplasmic reticulum (ER) stress provoked under diabetic conditions augments the expression of scavenger receptors on macrophages, promoting the uptake of oxidized low-density lipoprotein (ox-LDL) uptake and atherogenesis. The aim of the present study was to test the hypothesis that the chemical chaperone tauroursodeoxycholic acid (TUDCA) attenuates lipid accumulation in macrophages subjected to ER stress. Methods Cultured human macrophages were subjected to ER-stress by treating them with tunicamycin. Lipid-uptake by macrophages subjected to ER-stress in the presence or absence of TUDCA was assessed by oil red O staining and by assessing the cellular uptake of Dil-ox-LDL by fluorescence measurement. Protein levels and phosphorylation status of ER stress markers, insulin-signalling molecules and scavenger receptor were assessed by Western blotting. Results Treatment of cultured human macrophages with the ER-stressor tunicamycin caused an increase in the protein levels of CD-36, and augmentation of lipid-uptake both of which were inhibited by TUDCA. TUDCA-treatment inhibited tunicamycin-induced ER-stress as evidenced by the attenuation of phosphorylation of eukaryotic translation initiation factor-2α and glucose reactive protein-78. In addition, TUDCA improved insulin signaling in macrophages by augmenting Akt-phosphorylation and blunting c-Jun N-terminal kinase activity. Conclusion Inhibition of macrophage ER-stress may represent a potential strategy in preventing atherogenesis under diabetic conditions. PMID:19834331

  16. Occupational infections.

    PubMed

    Lim, V K E

    2009-06-01

    Many infections are associated with occupations. Involvement in a particular occupation may place the person at higher direct risk of contracting certain infections. In some instances the life-style associated with the occupation results in a higher risk of exposure to the infection. The link between the infection and the workplace is often missed by the attending physician. This may be due to a lack of awareness on the part of the physician. Sometimes a direct link can be difficult to prove without the use of sophisticated molecular epidemiological tests. This has led to gross under-diagnosis and under-reporting of such cases. It is however important that occupational infections be diagnosed as adequate preventive measures need to be implemented. Furthermore the patient may be eligible for monetary compensation under the relevant occupational safety laws of the country.

  17. [Occupational and non-occupational factors influencing health state of small and medium business workers].

    PubMed

    Fasikov, R M; Khuzhakhmetova, I B; Stepanov, E G

    2010-01-01

    Complex study of work conditions and health parameters of workers engaged into small and medium business proved that preserved and better health of these workers, prevention of occupational and occupationally mediated diseases necessitate federal and regional complex system of measures including legal basis, database on work conditions and their influence on small and medium business workers' health, occupational medicine training for employers and employees, more active involvement of medical institutioins into screening for occupational diseases.

  18. Cryptococcus neoformans-induced macrophage lysosome damage crucially contributes to fungal virulence1

    PubMed Central

    Davis, Michael J.; Eastman, Alison J.; Qiu, Yafeng; Gregorka, Brian; Kozel, Thomas R.; Osterholzer, John J.; Curtis, Jeffrey L.; Swanson, Joel A.; Olszewski, Michal A.

    2015-01-01

    Upon ingestion by macrophages, Cryptococcus neoformans (Cn) can survive and replicate intracellularly unless the macrophages become classically activated. The mechanism enabling intracellular replication is not fully understood; neither are the mechanisms which allow classical activation to counteract replication. Cn-induced lysosome damage was observed in infected murine bone marrow-derived macrophages, increased with time and required yeast viability. To demonstrate lysosome damage in the infected host, we developed a novel flow-cytometric method for measuring lysosome damage. Increased lysosome damage was found in Cn-containing lung cells compared to Cn–free cells. Among Cn-containing myeloid cells, recently recruited cells displayed lower damage than resident cells, consistent with the protective role of recruited macrophages. The magnitude of lysosome damage correlated with increased Cn replication. Experimental induction of lysosome damage increased Cn replication. Activation of macrophages with IFN-γ abolished macrophage lysosome damage and enabled increased killing of Cn. We conclude that induction of lysosome damage is an important Cn survival strategy and that classical activation of host macrophages counters replication by preventing damage. Thus, therapeutic strategies which decrease lysosomal damage, or increase resistance to such damage, could be valuable in treating cryptococcal infections. PMID:25637026

  19. The implementation of knowledge dissemination in the prevention of occupational skin diseases.

    PubMed

    Wilke, A; Bollmann, U; Cazzaniga, S; Hübner, A; John, S M; Karadzinska-Bislimovska, J; Mijakoski, D; Šimić, D; Simon, D; Sonsmann, F; Stoleski, S; Weinert, P; Wulfhorst, B

    2018-03-01

    Occupational skin diseases (OSD) have a high medical, social, economic and political impact. Knowledge dissemination from research activities to key stakeholders involved in health care is a prerequisite to make prevention effective. To study and prioritize different activity fields and stakeholders that are involved in the prevention of OSD, to reflect on their inter-relationships, to develop a strategic approach for knowledge dissemination and to develop a hands-on tool for OSD prevention projects METHODS: Seven different activity fields that are relevant in the prevention of OSD have been stepwise identified. This was followed by an impact analysis. Fifty-five international OSD experts rated the impact and the influence of the activity fields for the prevention of OSD with a standardized questionnaire. Activity fields identified to have a high impact in OSD prevention are the political system, mass media and industry. The political system has a strong but more indirect effect on the general population via the educational system, local public health services or the industry. The educational system, mass media, industry and local public health services have a strong direct impact on the OSD 'at risk' worker. Finally, a hands-on tool for future OSD prevention projects has been developed that addresses knowledge dissemination and different stakeholder needs. Systematic knowledge dissemination is important to make OSD prevention more effective and to close the gap between research and practice. This study provides guidance to identify stakeholders, strategies and dissemination channels for systematic knowledge dissemination which need to be adapted to country-specific structures, for example the social security system and healthcare systems. A key for successful knowledge dissemination is building linkages among different stakeholders, building strategic partnerships and gaining their support right from the inception phase of a project. © 2017 European Academy of

  20. Occupational Disease Registries-Characteristics and Experiences.

    PubMed

    Davoodi, Somayeh; Haghighi, Khosro Sadeghniat; Kalhori, Sharareh Rostam Niakan; Hosseini, Narges Shams; Mohammadzadeh, Zeinab; Safdari, Reza

    2017-06-01

    Due to growth of occupational diseases and also increase of public awareness about their consequences, attention to various aspects of diseases and improve occupational health and safety has found great importance. Therefore, there is the need for appropriate information management tools such as registries in order to recognitions of diseases patterns and then making decision about prevention, early detection and treatment of them. These registries have different characteristics in various countries according to their occupational health priorities. Aim of this study is evaluate dimensions of occupational diseases registries including objectives, data sources, responsible institutions, minimum data set, classification systems and process of registration in different countries. In this study, the papers were searched using the MEDLINE (PubMed) Google scholar, Scopus, ProQuest and Google. The search was done based on keyword in English for all motor engines including "occupational disease", "work related disease", "surveillance", "reporting", "registration system" and "registry" combined with name of the countries including all subheadings. After categorizing search findings in tables, results were compared with each other. Important aspects of the registries studied in ten countries including Finland, France, United Kingdom, Australia, Czech Republic, Malaysia, United States, Singapore, Russia and Turkey. The results show that surveyed countries have statistical, treatment and prevention objectives. Data sources in almost the rest of registries were physicians and employers. The minimum data sets in most of them consist of information about patient, disease, occupation and employer. Some of countries have special occupational related classification systems for themselves and some of them apply international classification systems such as ICD-10. Finally, the process of registration system was different in countries. Because occupational diseases are often

  1. Occupational Disease Registries–Characteristics and Experiences

    PubMed Central

    Davoodi, Somayeh; Haghighi, Khosro Sadeghniat; Kalhori, Sharareh Rostam Niakan; Hosseini, Narges Shams; Mohammadzadeh, Zeinab; Safdari, Reza

    2017-01-01

    Introduction: Due to growth of occupational diseases and also increase of public awareness about their consequences, attention to various aspects of diseases and improve occupational health and safety has found great importance. Therefore, there is the need for appropriate information management tools such as registries in order to recognitions of diseases patterns and then making decision about prevention, early detection and treatment of them. These registries have different characteristics in various countries according to their occupational health priorities. Aim: Aim of this study is evaluate dimensions of occupational diseases registries including objectives, data sources, responsible institutions, minimum data set, classification systems and process of registration in different countries. Material and Methods: In this study, the papers were searched using the MEDLINE (PubMed) Google scholar, Scopus, ProQuest and Google. The search was done based on keyword in English for all motor engines including “occupational disease”, “work related disease”, “surveillance”, “reporting”, “registration system” and “registry” combined with name of the countries including all subheadings. After categorizing search findings in tables, results were compared with each other. Results: Important aspects of the registries studied in ten countries including Finland, France, United Kingdom, Australia, Czech Republic, Malaysia, United States, Singapore, Russia and Turkey. The results show that surveyed countries have statistical, treatment and prevention objectives. Data sources in almost the rest of registries were physicians and employers. The minimum data sets in most of them consist of information about patient, disease, occupation and employer. Some of countries have special occupational related classification systems for themselves and some of them apply international classification systems such as ICD-10. Finally, the process of registration system was

  2. Implementing person-environment approaches to prevent falls: a qualitative inquiry in applying the Westmead approach to occupational therapy home visits.

    PubMed

    Clemson, Lindy; Donaldson, Alex; Hill, Keith; Day, Lesley

    2014-10-01

    Despite evidence of the effectiveness of home safety interventions for preventing falls, there is limited uptake of such interventions within community services. Therefore, as part of a broader translational project, we explored issues underlying the implementation of an evidence-based home safety fall prevention intervention. We conducted in-depth interviews with eight occupational therapists and two programme coordinators engaged to deliver a home safety fall prevention intervention. Six community health centres within two metropolitan regions of Melbourne, Australia participated. The RE-AIM framework and Diffusion of Innovations theory underpinned the interviews which examine the enablers and barriers to implementing a home safety fall prevention intervention and integrating it into routine community preventive practice. Analysis involved thematic and content analysis. Investment in the home safety for fall prevention intervention was supported and valued by coordinators and therapists alike, and a number of themes emerged which influenced implementation of this intervention. These included issues of: compatibility with organisational processes, individual practitioner practices and skills, a prevention approach, and client expectations; relative advantage in terms of flexibility of the process, client engagement and regional capacity building; complexity of implementing the intervention; and observability related to the invisible nature of fall prevention outcomes. Implementation of this home safety fall prevention intervention was influenced by a range of interrelated organisational, practitioner and client related factors. The findings from this project provide insights into, and opportunities to increase the sustainable implementation of the home safety fall prevention intervention into practice. © 2014 Occupational Therapy Australia.

  3. Aggregate Exposure and Cumulative Risk Assessment—Integrating Occupational and Non-occupational Risk Factors

    PubMed Central

    Lentz, T. J.; Dotson, G. S.; Williams, P. R.D.; Maier, A.; Gadagbui, B.; Pandalai, S. P.; Lamba, A.; Hearl, F.; Mumtaz, M.

    2015-01-01

    Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational. PMID:26583907

  4. Aggregate Exposure and Cumulative Risk Assessment--Integrating Occupational and Non-occupational Risk Factors.

    PubMed

    Lentz, T J; Dotson, G S; Williams, P R D; Maier, A; Gadagbui, B; Pandalai, S P; Lamba, A; Hearl, F; Mumtaz, M

    2015-01-01

    Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational.

  5. [Cardiovascular risk, occupation and exposure to occupational carcinogens in a group of workers in Salamanca].

    PubMed

    González-Sánchez, Jesús

    2015-01-01

    Identify the cardiovascular risk factors in a group of workers in the province of Salamanca, protected by external prevention services, as regards exposure to occupational carcinogens, by sector of activity and gender. An observational descriptive epidemiological study was conducted. The sample selection was by stratified random sampling in each entity. The variables collected by questionnaire were, sociodemographic characteristics, exposure to occupational carcinogens, and cardiovascular risk factors (smoking, hypertension, dyslipidemia, and diabetes), using the clinical-work histories as a source of information. Statistically significant differences were observed in cardiovascular risk according to the exposure to occupational carcinogens (p <0.001), primarily among workers in the industry sector. A total of 32% of the workers in the province of Salamanca was exposed to some occupational carcinogen. Women were more exposed in the service sector and men in the agriculture and livestock sector. Nearly one third of the workers belonging to the external prevention services of the province of Salamanca, were exposed to some kind of occupational carcinogens. The most frequent being biological risks, solvent products, and silica, which were above the national mean of exposure. It is important to consider the exposure to occupational carcinogens in the implementation of interventions in the prevention of cardiovascular risk in the work place. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  6. Regulation of endotoxin-induced inhibition of macrophage migration by fresh serum.

    PubMed Central

    Heilman, D H

    1977-01-01

    Purified endotoxin (LPS) caused macrophage migration inhibition (MMI) in capillary tube cultures of guinea pig peritoneal macrophages in medium prepared with 15% fresh-frozen guinea pig serum. The inactivation of serum by heating at 56 degrees C for 30 min or by zymosan absorption prevented LPS-induced MMI. LPS was fully inhibitory in fresh C4-deficient guinea pig serum. Heat treatment of normal serum at 50 to 52 degrees C for 30 min to inactivate the alternate complement (C) pathway prevented or significantly decreased LPS-induced MMI, but heating C4-deficient serum at 50 to 52 degrees C for 30 min prevented LPS-MMI in all instances. These results suggest that the reaction was effected via the alternate C pathway but that some inhibition of migration was permitted via the classical C pathway, presumably due to antibodies for LPS in some normal sera. Pretreatment of normal serum with cobra venom factor decreased or prevented LPS-MMI in most instances, but similar results were obtained with C4-deficient serum. Experiments with chelated sera were unsuccessful because of the immobilization of macrophages by 10 mM ethylenediamine-tetraacetic acid and by 10 mM Mg-ethyleneglycol-bis (beta-aminoethyl)-N,N-tetraacetic acid. Low doses of concanavalin A and staphylococcal enterotoxin B and large doses of pokeweed mitogen caused MMI in "inactivated serum" medium, but MMI was enhanced in fresh serum. PMID:330407

  7. [Hazard assessment and occupational safety measures in surgery : Relevant knowledge on occupational medicine].

    PubMed

    Darius, S; Meyer, F; Böckelmann, I

    2016-11-01

    Surgeons routinely work in an environment with occupational risks and hazards about which they are often uninformed. Based on the currently available scientific literature this review article describes the various hazards in the operating theater and their effects on personnel, particularly from the surgical perspective. A further aim of this article is to describe the occupational safety measures to reduce the burdens and to maintain the long-term health of personnel. Ultimately, surgeons should be equipped with the necessary knowledge for implementing hazard assessments according to the German Occupational Health and Safety Act. Surgeons are exposed to increased risks and hazards by working in awkward positions with a high risk for musculoskeletal pain and injuries. They are also commonly exposed to inhalational anesthetics, surgical smoke, radiation, noise and infectious agents. Furthermore, the mental and emotional stress associated with these activities is also high. Meaningful occupational safety measures for reduction of burdens are from a technical aspect the installation of effective air extraction systems, measures to reduce exposure to radiation and noise and the use of safer instruments to prevent needle stick injuries. Furthermore, individual occupational safety measures, such as the use of personal protective equipment (e.g. radiation protective clothing and double gloves) must be observed. The consistent implementation and also adherence to these described occupational safety measures and regulations can reduce the burden on operating theater personnel and contribute to maintaining health. Furthermore, periodic preventive healthcare controls and health checks by the company medical officer and individually initiated additional prevention measures can be a sensible augmentation to these safety measures.

  8. Inhibition of high glucose-induced inflammatory response and macrophage infiltration by a novel curcumin derivative prevents renal injury in diabetic rats

    PubMed Central

    Pan, Yong; Wang, Yi; Cai, Lu; Cai, Yuepiao; Hu, Jie; Yu, Congcong; Li, Jianling; Feng, Zhiguo; Yang, Shulin; Li, Xiaokun; Liang, Guang

    2012-01-01

    BACKGROUND AND PURPOSE Inflammation is involved in the development and/or progression of many diseases including diabetic complications. Investigations on novel anti-inflammatory agents may offer new approaches for the prevention of diabetic nephropathy. Our previous bioscreening of synthetic analogues of curcumin revealed C66 as a novel anti-inflammatory compound against LPS challenge in macrophages. In this study, we hypothesized that C66 affects high glucose (HG)-induced inflammation profiles in vitro and in vivo and then prevents renal injury in diabetic rats via its anti-inflammatory actions. EXPERIMENTAL APPROACH Primary peritoneal macrophages (MPM), prepared from C57BL/6 mice, were treated with HG in the presence or absence of C66. Diabetes was induced in Sprague–Dawley rats with streptozotocin, and the effects of C66 (0.2, 1.0 or 5.0 mg·kg−1), administered daily for 6 weeks, on plasma TNF-α levels and expression of inflammatory genes in the kidney were assessed. KEY RESULTS Pretreatment of MPMs with C66 reduced HG-stimulated production of TNF-α and NO, inhibited HG-induced IL-1β, TNF-α, IL-6, IL-12, COX-2 and iNOS mRNA transcription, and the activation of JNK/NF-kB signalling. In vivo, C66 inhibited the increased plasma TNF-α levels and renal inflammatory gene expression, improved histological abnormalities and fibrosis of diabetic kidney, but did not affect the hyperglycaemia in these diabetic rats. CONCLUSIONS AND IMPLICATIONS The anti-inflammatory effects of C66 are mediated by inhibiting HG-induced activation of the JNK/NF-κB pathway, rather than by reducing blood glucose in diabetic rats. This novel compound is a potential anti-inflammatory agent and might be beneficial for the prevention of diabetic nephropathy. PMID:22242942

  9. Embryonic Stem Cells Promoting Macrophage Survival and Function are Crucial for Teratoma Development

    PubMed Central

    Chen, Tianxiang; Wang, Xi; Guo, Lei; Wu, Mingmei; Duan, Zhaoxia; Lv, Jing; Tai, Wenjiao; Renganathan, Hemamalini; Didier, Ruth; Li, Jinhua; Sun, Dongming; Chen, Xiaoming; He, Xijing; Fan, Jianqing; Young, Wise; Ren, Yi

    2014-01-01

    Stem cell therapies have had tremendous potential application for many diseases in recent years. However, the tumorigenic properties of stem cells restrict their potential clinical application; therefore, strategies for reducing the tumorigenic potential of stem cells must be established prior to transplantation. We have demonstrated that syngeneic transplantation of embryonic stem cells (ESCs) provokes an inflammatory response that involves the rapid recruitment of bone marrow-derived macrophages (BMDMs). ESCs are able to prevent mature macrophages from macrophage colony-stimulating factor (M-CSF) withdrawal-induced apoptosis, and thus prolong macrophage lifespan significantly by blocking various apoptotic pathways in an M-CSF-independent manner. ESCs express and secrete IL-34, which may be responsible for ESC-promoted macrophage survival. This anti-apoptotic effect of ESCs involves activation of extracellular signal-regulated kinase (ERK)1/2 and PI3K/Akt pathways and thus, inhibition of ERK1/2 and PI3K/AKT activation decreases ESC-induced macrophage survival. Functionally, ESC-treated macrophages also showed a higher level of phagocytic activity. ESCs further serve to polarize BMDMs into M2-like macrophages that exhibit most tumor-associated macrophage phenotypic and functional features. ESC-educated macrophages produce high levels of arginase-1, Tie-2, and TNF-α, which participate in angiogenesis and contribute to teratoma progression. Our study suggests that induction of M2-like macrophage activation is an important mechanism for teratoma development. Strategies targeting macrophages to inhibit teratoma development would increase the safety of ESC-based therapies, inasmuch as the depletion of macrophages completely inhibits ESC-induced angiogenesis and teratoma development. PMID:25071759

  10. Individual and occupational factors related to fatal occupational injuries: a case-control study.

    PubMed

    Villanueva, Vicent; Garcia, Ana M

    2011-01-01

    This study has been designed in order to identify factors increasing the risk of a fatal outcome when occupational accidents occur. The aim is to provide further evidence for the design and implementation of preventive measures in occupational settings. The Spanish Ministry of Labour registry of occupational injuries causing absence from work includes information on individual and occupational characteristics of injured workers and events. Registered fatal occupational injuries in 2001 (n=539) were compared to a sample of non-fatal injuries in the same year (n=3493). Risks for a fatal result of occupational injuries, adjusted by individual and occupational factors significantly associated, were obtained through logistic regression models. Compared to non-fatal injuries, fatal occupational injuries were mostly produced by trapping or by natural causes, mostly related to elevation and transport devices and power generators, and injured parts of body more frequently affected were head, multiple parts or internal organs. Adjusted analyses showed increased risk of fatality after an occupational injury for males (adjusted odds ratio aOR=10.92; 95%CI 4.80-24.84) and temporary workers (aOR=5.18; 95%CI 2.63-10.18), and the risk increased with age and with advancing hour of the work shift (p for trends <0.01). Injuries taking place out of the usual occupational setting (aOR=2.85, 95%CI 2.27-3.59), or carrying out atypical tasks (aOR=2.08; 95%CI 1.27-3.39) showed increased risks of a fatal result too, as occupational accidents in agricultural or construction companies. These data can help to select and define priorities for programmes aimed to prevent fatal consequences of occupational injuries. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. The alveolar macrophage.

    PubMed

    Bowden, D H

    1984-04-01

    The pulmonary macrophagic system is critical to the defense of the lung, keeping the alveoli clean and sterile and responding on demand with an adaptive outpouring of new cells into the air sacs. Under basal conditions alveolar macrophages, in common with other mononuclear phagocytes, are derived from the bone marrow. A population of macrophage precursors within the pulmonary interstitium provides a reserve pool capable of proliferation and delivery of phagocytes in response to unusually heavy loads of inhaled particles. This reserve system also produces macrophages when monocytic precursors in the bone marrow are depleted by diseases such as leukemia. The alveolar macrophage is destined to ingest particulate matter and to be eliminated along the mucociliary pathway; clearance by lymphatics is of minor importance and macrophages probably do not recross the alveolar epithelium to reach the pulmonary interstitial compartment. Although the protective role of the macrophage is dominant, this cell may participate, directly or indirectly, in the genesis of two major groups of chronic pulmonary disease, interstitial fibrosis and emphysema. Such inappropriate responses involve interactions with fibroblastic cells and tissue injury initiated by proteases secreted by the macrophage.

  12. Actin-based motility allows Listeria monocytogenes to avoid autophagy in the macrophage cytosol.

    PubMed

    Cheng, Mandy I; Chen, Chen; Engström, Patrik; Portnoy, Daniel A; Mitchell, Gabriel

    2018-05-03

    Listeria monocytogenes grows in the host cytosol and uses the surface protein ActA to promote actin polymerisation and mediate actin-based motility. ActA, along with two secreted bacterial phospholipases C, also mediates avoidance from autophagy, a degradative process that targets intracellular microbes. Although it is known that ActA prevents autophagic recognition of L. monocytogenes in epithelial cells by masking the bacterial surface with host factors, the relative roles of actin polymerisation and actin-based motility in autophagy avoidance are unclear in macrophages. Using pharmacological inhibition of actin polymerisation and a collection of actA mutants, we found that actin polymerisation prevented the colocalisation of L. monocytogenes with polyubiquitin, the autophagy receptor p62, and the autophagy protein LC3 during macrophage infection. In addition, the ability of L. monocytogenes to stimulate actin polymerisation promoted autophagy avoidance and growth in macrophages in the absence of phospholipases C. Time-lapse microscopy using green fluorescent protein-LC3 macrophages and a probe for filamentous actin showed that bacteria undergoing actin-based motility moved away from LC3-positive membranes. Collectively, these results suggested that although actin polymerisation protects the bacterial surface from autophagic recognition, actin-based motility allows escape of L. monocytogenes from autophagic membranes in the macrophage cytosol. © 2018 John Wiley & Sons Ltd.

  13. Heterogeneity of macrophages in injured trigeminal nerves: cytokine/chemokine expressing vs. phagocytic macrophages.

    PubMed

    Lee, SeungHwan; Zhang, Ji

    2012-08-01

    Macrophages are important immune effector cells in both innate and adaptive immune responses. Injury to peripheral nerves triggers activation of resident macrophages and infiltration of haematogenous macrophages, which they play critical roles in Wallerian degeneration and neuropathic pain. As macrophages are able to change their phenotypes in response to environment cues, we attempt to identify distinct phenotypes of macrophages in injured nerves and to understand the potential contribution of each macrophage subpopulation to the genesis of neuropathic pain associated with nerve injury. Rat mental nerves (terminal branches of trigeminal nerve) were loosely ligated. Sensitivity to mechanical stimuli at the lower lip area was monitored using calibrated von Frey Hairs. We examined the expression pattern of Iba-1, MAC1 and ED1 which allow us to reveal the immunophenotypes of macrophages at different time points post-injury. Functional status of each macrophage subpopulation was further investigated by colocalization with cytokines/chemokines, myelin basic protein and MHC II antigen, which reflect respectively secretory, phagocytic and antigen presentation properties of activated macrophages. Following nerve injury, a burst of Iba-1(+) macrophages was found in injured mental nerves. Among them, we detected two major immunophenotypes: MAC1(+) cytokines/chemokines secreting macrophages and ED1(+) phagocytic macrophages. Small, round shaped MAC1(+) macrophages were distributed essentially around the lesion site and existed only at early time points. Large, irregular and foamy ED1(+) macrophages were found among damaged nerve fibers and they persisted for at least 3 months post-injury. Although ED1(+) macrophages did not secrete inflammatory mediators, they were able to express neurotransmitter CGRP and MHC II at later time points. In parallel, we observed that mechanical allodynia developed after the nerve ligation was at its lowest level within 1 month. Although slightly

  14. Macrophage polarization differs between apical granulomas, radicular cysts, and dentigerous cysts.

    PubMed

    Weber, Manuel; Schlittenbauer, Tilo; Moebius, Patrick; Büttner-Herold, Maike; Ries, Jutta; Preidl, Raimund; Geppert, Carol-Immanuel; Neukam, Friedrich W; Wehrhan, Falk

    2018-01-01

    Apical periodontitis can appear clinically as apical granulomas or radicular cysts. There is evidence that immunologic factors are involved in the pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main regulator of tissue homeostasis and differentiation. There are no studies comparing macrophage polarization in apical granulomas, radicular cysts, and dentigerous cysts. Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-, CD163-, and MRC1-positive macrophages were detected by immunohistochemical methods. TMAs were digitized, and the expression of macrophage markers was quantitatively assessed. Radicular cysts are characterized by M1 polarization of macrophages while apical granulomas show a significantly higher degree of M2 polarization. Dentigerous cysts have a significantly lower M1 polarization than both analyzed periapical lesions (apical granulomas and radicular cysts) and accordingly, a significantly higher M2 polarization than radicular cysts. Macrophage cell density in dentigerous cysts is significantly lower than in the periapical lesions. The development of apical periodontitis towards apical granulomas or radicular cysts might be directed by macrophage polarization. Radicular cyst formation is associated with an increased M1 polarization of infiltrating macrophages. In contrast to radicular cysts, dentigerous cysts are characterized by a low macrophage infiltration and a high degree of M2 polarization, possibly reflecting their developmental rather than inflammatory origin. As M1 polarization of macrophages is triggered by bacterial antigens, these results underline the need for sufficient bacterial clearance during endodontic treatment to prevent a possible M1 macrophage-derived stimulus for radicular cyst

  15. Melanocortin 1 Receptor Signaling Regulates Cholesterol Transport in Macrophages.

    PubMed

    Rinne, Petteri; Rami, Martina; Nuutinen, Salla; Santovito, Donato; van der Vorst, Emiel P C; Guillamat-Prats, Raquel; Lyytikäinen, Leo-Pekka; Raitoharju, Emma; Oksala, Niku; Ring, Larisa; Cai, Minying; Hruby, Victor J; Lehtimäki, Terho; Weber, Christian; Steffens, Sabine

    2017-07-04

    The melanocortin 1 receptor (MC1-R) is expressed by monocytes and macrophages, where it exerts anti-inflammatory actions on stimulation with its natural ligand α-melanocyte-stimulating hormone. The present study was designed to investigate the specific role of MC1-R in the context of atherosclerosis and possible regulatory pathways of MC1-R beyond anti-inflammation. Human and mouse atherosclerotic samples and primary mouse macrophages were used to study the regulatory functions of MC1-R. The impact of pharmacological MC1-R activation on atherosclerosis was assessed in apolipoprotein E-deficient mice. Characterization of human and mouse atherosclerotic plaques revealed that MC1-R expression localizes in lesional macrophages and is significantly associated with the ATP-binding cassette transporters ABCA1 and ABCG1, which are responsible for initiating reverse cholesterol transport. Using bone marrow-derived macrophages, we observed that α-melanocyte-stimulating hormone and selective MC1-R agonists similarly promoted cholesterol efflux, which is a counterregulatory mechanism against foam cell formation. Mechanistically, MC1-R activation upregulated the levels of ABCA1 and ABCG1. These effects were accompanied by a reduction in cell surface CD36 expression and in cholesterol uptake, further protecting macrophages from excessive lipid accumulation. Conversely, macrophages deficient in functional MC1-R displayed a phenotype with impaired efflux and enhanced uptake of cholesterol. Pharmacological targeting of MC1-R in atherosclerotic apolipoprotein E-deficient mice reduced plasma cholesterol levels and aortic CD36 expression and increased plaque ABCG1 expression and signs of plaque stability. Our findings identify a novel role for MC1-R in macrophage cholesterol transport. Activation of MC1-R confers protection against macrophage foam cell formation through a dual mechanism: It prevents cholesterol uptake while concomitantly promoting ABCA1- and ABCG1-mediated reverse

  16. Minimum standards on prevention, diagnosis and treatment of occupational and work-related skin diseases in Europe - position paper of the COST Action StanDerm (TD 1206).

    PubMed

    Alfonso, J H; Bauer, A; Bensefa-Colas, L; Boman, A; Bubas, M; Constandt, L; Crepy, M N; Goncalo, M; Macan, J; Mahler, V; Mijakoski, D; Ramada Rodilla, J M; Rustemeyer, T; Spring, P; John, S M; Uter, W; Wilkinson, M; Giménez-Arnau, A M

    2017-06-01

    Skin diseases constitute up to 40% of all notified occupational diseases in most European countries, predominantly comprising contact dermatitis, contact urticaria, and skin cancer. While insufficient prevention of work-related skin diseases (WRSD) is a top-priority problem in Europe, common standards for prevention of these conditions are lacking. To develop common European standards on prevention and management of WRSD and occupational skin diseases (OSD). Consensus amongst experts within occupational dermatology was achieved with regard to the definition of minimum evidence-based standards on prevention and management of WRSD/OSD. By definition, WRSDs/OSDs are (partially or fully) caused by occupational exposure. The definition of OSD sensu stricto additionally includes diverging national legal requirements, with an impact on registration, prevention, management, and compensation. With the implementation of the classification of WRSD/OSD in the International Classification of Diseases (ICD) 11th Revision in future, a valid surveillance and comparability across countries will be possible. Currently, WRDS and OSD are still under-reported. Depending on legislation and regulations, huge differences exist in notification procedures in Europe, although notification is crucial to prevent chronic and relapsing disease. Facilities for early diagnosis, essential for individual patient management, should be based on existing guidelines and include a multidisciplinary approach. Patch testing is essential if contact dermatitis persists or relapses. Workplace exposure assessment of WRSD/OSD requires full labelling of product ingredients on material safety data sheets helping to identify allergens, irritants and skin carcinogens. Comparable standards in primary, secondary and tertiary prevention must be established in Europe to reduce the burden of WRSD/OSD in Europe. The adoption of common European standards on prevention of WRSD/OSD will contribute to reduce the incidence of

  17. [Registry of the Italian Institute for Occupational Prevention and Safety of local productive units: methodology and structure].

    PubMed

    Scarselli, A; Leva, A; Campo, G; Marconi, M; Nesti, M; Erba, P

    2005-01-01

    The Italian Institute for Occupational Prevention and Safety (ISPESL) carried out a register of enterprises operating in industry, services and agriculture sector to provide information on their location, economical activity and occupational data. This database has been built merging administrative files from the National Institute of Social Security (INPS) and the Computer Science Society of Italian Chambers of Commerce (InfoCamere). Enterprises have been classified by economic sector - in accordance with ISTAT (National Statistics Institute) "Ateco91" classification--and by accuracy level of the record linkage. In details, three different subsystems have been set up: (A) enterprises satisfying linkage; (B) enterprises in InfoCamere file not linked with INPS file; (C) enterprises in INPS file not linked with InfoCamere file. In the whole, 6.026.676 factories have been collected, of which 1.188.784 in group A, 4.543.091 in group B and 294.801 in group C. Establishing a database of information on industries may be useful to improve preventive programs and to plan health care surveillance systems.

  18. Supporting our military families: a case for a larger role for occupational therapy in prevention and mental health care.

    PubMed

    Cogan, Alison M

    2014-01-01

    More than 2 million U.S. military servicemembers have deployed to Afghanistan or Iraq since September 11, 2001. Unlike during prior conflicts, many servicemembers leave spouses and children behind. Long, multiple deployments cause strain on family at home, with new challenges arising when servicemembers return from combat and reintegrate into family and civilian life. In World Wars I and II, occupational therapy practitioners played a significant role in supporting servicemember reintegration. However, their presence in program delivery in this practice area is limited. Occupational therapy researchers and practitioners can make a valuable contribution by helping families tailor daily activities and routines to address challenges and optimize health and wellness. However, barriers such as reimbursement for services, workforce availability, and access to military families have limited the profession's full engagement. Advocacy is needed to help establish occupational therapy as a key component of the mental and preventive health care teams serving military servicemembers. Copyright © 2014 by the American Occupational Therapy Association, Inc.

  19. [Individual prevention of occupational contact dermatitis: protective gloves and skin protection recommendations as part of the patient management scheme by the public statutory employers' liability insurance].

    PubMed

    Wilke, A; Skudlik, C; Sonsmann, F K

    2018-05-02

    The dermatologist's procedure is a pivotal tool for early recognition of occupational contact dermatitis (OCD), for reporting OCD cases to the statutory accident insurance and for treating the diseases. The employer is in charge of implementing skin protection measures at the workplace. However, in terms of an individual prevention approach it may be necessary to propose targeted skin protection recommendations in specific patient cases. The patient's own skin protection behavior significantly contributes to regenerating and maintaining healthy skin. This behavior includes the use of occupational skin products, and in particular the correct use of appropriately selected protective gloves. Protective gloves are the most important personal protective measure in the prevention of OCD. Prevention services, occupational health and safety specialists, occupational physicians and centers specialized in occupational dermatology can support the identification of suitable protective measures. Nowadays, suitable protective gloves exist for (almost) every occupational activity and exposure. However, improper use in practice can become a risk factor by itself for the skin (e. g., incorrectly used gloves). Therefore, it is of utmost importance to identify application errors, to educate patients in terms of skin protection and to motivate them to perform an appropriate skin protection behavior. With particular focus on protective gloves, this article gives an overview of various types, materials and potentially glove-related allergens, presents strategies for reducing occlusion effects and discusses some typical application errors and solutions.

  20. Differential regulation of macrophage inflammatory activation by fibrin and fibrinogen.

    PubMed

    Hsieh, Jessica Y; Smith, Tim D; Meli, Vijaykumar S; Tran, Thi N; Botvinick, Elliot L; Liu, Wendy F

    2017-01-01

    Fibrin is a major component of the provisional extracellular matrix formed during tissue repair following injury, and enables cell infiltration and anchoring at the wound site. Macrophages are dynamic regulators of this process, advancing and resolving inflammation in response to cues in their microenvironment. Although much is known about how soluble factors such as cytokines and chemokines regulate macrophage polarization, less is understood about how insoluble and adhesive cues, specifically the blood coagulation matrix fibrin, influence macrophage behavior. In this study, we observed that fibrin and its precursor fibrinogen elicit distinct macrophage functions. Culturing macrophages on fibrin gels fabricated by combining fibrinogen with thrombin stimulated secretion of the anti-inflammatory cytokine, interleukin-10 (IL-10). In contrast, exposure of macrophages to soluble fibrinogen stimulated high levels of inflammatory cytokine tumor necrosis factor alpha (TNF-α). Macrophages maintained their anti-inflammatory behavior when cultured on fibrin gels in the presence of soluble fibrinogen. In addition, adhesion to fibrin matrices inhibited TNF-α production in response to stimulation with LPS and IFN-γ, cytokines known to promote inflammatory macrophage polarization. Our data demonstrate that fibrin exerts a protective effect on macrophages, preventing inflammatory activation by stimuli including fibrinogen, LPS, and IFN-γ. Together, our study suggests that the presentation of fibrin(ogen) may be a key switch in regulating macrophage phenotype behavior, and this feature may provide a valuable immunomodulatory strategy for tissue healing and regeneration. Fibrin is a fibrous protein resulting from blood clotting and provides a provisional matrix into which cells migrate and to which they adhere during wound healing. Macrophages play an important role in this process, and are needed for both advancing and resolving inflammation. We demonstrate that culture of

  1. Exposure to Stress: Occupational Hazards in Hospitals

    MedlinePlus

    EXPOSURE TO STRESS Occupational Hazards in Hospitals DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health Exposure to Stress Occupational Hazards in Hospitals DEPARTMENT OF HEALTH AND ...

  2. The cost effectiveness of occupational health interventions: preventing occupational back pain.

    PubMed

    Lahiri, Supriya; Markkanen, Pia; Levenstein, Charles

    2005-12-01

    Occupational back pain exacts a toll on society with concomitant economic losses; it is imperative to evaluate the cost-effectiveness of interventions to reduce the relevant ergonomic stressors at work. This study estimates and evaluates the average and incremental cost-effectiveness ratios (CERs) of specific interventions for the prevention of occupationally induced back pain for the World Health Organization (WHO) defined subregions of the world. Four back-pain interventions were selected from the literature: training (T), engineering controls (EC), engineering controls and training (EC&T), and a comprehensive full ergonomics program (EP) for evaluation. A simulation model for a 100-year time horizon, developed by the WHO CHOICE initiative project was used to estimate the effectiveness of the interventions in healthy year equivalents. The intervention costs were adjusted for all WHO subregions. In all of the subregions, training was the most cost-effective with CERs varying from 74 dollars per healthy life years gained in the subregion comprising of Egypt, Iraq, Morocco, Yemen (EMROD) to approximately 567 dollars in the subregion covering Canada and the United States (AMROA). Training is considered to be very cost-effective and would be the first choice option where resources are scarce. However, the overall effectiveness of training is low. Although other interventions such as engineering controls and total ergonomic interventions are relatively more expensive, the addition to health outcome through these interventions is much higher. The difference in the CERs for training and other engineering controls and full ergonomic interventions is relatively small for most of the industrialized regions of the world. It is clear from the ranked CERs and incremental CERs over the different subregions that in most of the industrialized regions of the world additional resources, if they become available, should go straight to the full ergonomics program. The model results

  3. Macrophages Inhibit Neovascularization in a Murine Model of Age-Related Macular Degeneration

    PubMed Central

    Apte, Rajendra S; Richter, Jennifer; Herndon, John; Ferguson, Thomas A

    2006-01-01

    Background Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 y of age in at least three continents. Choroidal neovascularization (CNV) is the process by which abnormal blood vessels develop underneath the retina. CNV develops in 10% of patients with AMD but accounts for up to 90% of the blindness from AMD. Although the precise etiology of CNV in AMD remains unknown, the macrophage component of the inflammatory response, which has been shown to promote tumor growth and support atherosclerotic plaque formation, is thought to stimulate aberrant angiogenesis in blinding eye diseases. The current theory is that macrophage infiltration promotes the development of neovascularization in CNV. Methods and Findings We examined the role of macrophages in a mouse model of CNV. IL-10 −/− mice, which have increased inflammation in response to diverse stimuli, have significantly reduced CNV with increased macrophage infiltrates compared to wild type. Prevention of macrophage entry into the eye promoted neovascularization while direct injection of macrophages significantly inhibited CNV. Inhibition by macrophages was mediated by the TNF family death molecule Fas ligand (CD95-ligand). Conclusions Immune vascular interactions can be highly complex. Normal macrophage function is critical in controlling pathologic neovascularization in the eye. IL-10 regulates macrophage activity in the eye and is an attractive therapeutic target in order to suppress or inhibit CNV in AMD that can otherwise lead to blindness. PMID:16903779

  4. [A quality assessment of notified occupational diseases submitted to the National Occupational Environment Service].

    PubMed

    Lander, F; Bach, B; Laursen, P

    1999-08-09

    The aim of this study was to assess the quality of a consecutive sample of occupational disease notifications submitted to the National Working Environment Service during 1994. The sample consisted of 860 notifications describing occupational diseases among persons working in companies situated in the county of Vejle. The data information e.g. company name and address, time of employment, harmful exposure and disease, were registered. An overall data quality assessment was performed including evaluation of the etiological connection between described occupational exposure and disease and potential preventive perspectives. The study showed that the notified informations in general were adequate, but doctors need to pay more attention to dose description of the harmful exposure. About 80% of the notifications presented an adequate connection between occupational exposure and disease. Only half of the notifications described preventable and recent (less than five years) harmful exposure. In conclusion, the Danish occupational disease notification system is in general of a high standard, and the National Working Environment Service could make more use of doctors' information provided in these notifications.

  5. Acid sphingomyelinase-deficient macrophages have defective cholesterol trafficking and efflux.

    PubMed

    Leventhal, A R; Chen, W; Tall, A R; Tabas, I

    2001-11-30

    Cholesterol efflux from macrophage foam cells, a key step in reverse cholesterol transport, requires trafficking of cholesterol from intracellular sites to the plasma membrane. Sphingomyelin is a cholesterol-binding molecule that transiently exists with cholesterol in endosomes and lysosomes but is rapidly hydrolyzed by lysosomal sphingomyelinase (L-SMase), a product of the acid sphingomyelinase (ASM) gene. We therefore hypothesized that sphingomyelin hydrolysis by L-SMase enables cholesterol efflux by preventing cholesterol sequestration by sphingomyelin. Macrophages from wild-type and ASM knockout mice were incubated with [(3)H]cholesteryl ester-labeled acetyl-LDL and then exposed to apolipoprotein A-I or high density lipoprotein. In both cases, [(3)H]cholesterol efflux was decreased substantially in the ASM knockout macrophages. Similar results were shown for ASM knockout macrophages labeled long-term with [(3)H]cholesterol added directly to medium, but not for those labeled for a short period, suggesting defective efflux from intracellular stores but not from the plasma membrane. Cholesterol trafficking to acyl-coenzyme A:cholesterol acyltransferase (ACAT) was also defective in ASM knockout macrophages. Using filipin to probe cholesterol in macrophages incubated with acetyl-LDL, we found there was modest staining in the plasma membrane of wild-type macrophages but bright, perinuclear fluorescence in ASM knockout macrophages. Last, when wild-type macrophages were incubated with excess sphingomyelin to "saturate" L-SMase, [(3)H]cholesterol efflux was decreased. Thus, sphingomyelin accumulation due to L-SMase deficiency leads to defective cholesterol trafficking and efflux, which we propose is due to sequestration of cholesterol by sphingomyelin and possibly other mechanisms. This model may explain the low plasma high density lipoprotein found in ASM-deficient humans and may implicate L-SMase deficiency and/or sphingomyelin enrichment of lipoproteins as novel

  6. DHA Suppresses Primary Macrophage Inflammatory Responses via Notch 1/ Jagged 1 Signaling

    PubMed Central

    Ali, Mehboob; Heyob, Kathryn; Rogers, Lynette K.

    2016-01-01

    Persistent macrophages were observed in the lungs of murine offspring exposed to maternal LPS and neonatal hyperoxia. Maternal docosahexaenoic acid (DHA) supplementation prevented the accumulation of macrophages and improved lung development. We hypothesized that these macrophages are responsible for pathologies observed in this model and the effects of DHA supplementation. Primary macrophages were isolated from adult mice fed standard chow, control diets, or DHA supplemented diets. Macrophages were exposed to hyperoxia (O2) for 24 h and LPS for 6 h or 24 h. Our data demonstrate significant attenuation of Notch 1 and Jagged 1 protein levels in response to DHA supplementation in vivo but similar results were not evident in macrophages isolated from mice fed standard chow and supplemented with DHA in vitro. Co-culture of activated macrophages with MLE12 epithelial cells resulted in the release of high mobility group box 1 and leukotriene B4 from the epithelial cells and this release was attenuated by DHA supplementation. Collectively, our data indicate that long term supplementation with DHA as observed in vivo, resulted in deceased Notch 1/Jagged 1 protein expression however, DHA supplementation in vitro was sufficient to suppress release LTB4 and to protect epithelial cells in co-culture. PMID:26940787

  7. DHA Suppresses Primary Macrophage Inflammatory Responses via Notch 1/ Jagged 1 Signaling.

    PubMed

    Ali, Mehboob; Heyob, Kathryn; Rogers, Lynette K

    2016-03-04

    Persistent macrophages were observed in the lungs of murine offspring exposed to maternal LPS and neonatal hyperoxia. Maternal docosahexaenoic acid (DHA) supplementation prevented the accumulation of macrophages and improved lung development. We hypothesized that these macrophages are responsible for pathologies observed in this model and the effects of DHA supplementation. Primary macrophages were isolated from adult mice fed standard chow, control diets, or DHA supplemented diets. Macrophages were exposed to hyperoxia (O2) for 24 h and LPS for 6 h or 24 h. Our data demonstrate significant attenuation of Notch 1 and Jagged 1 protein levels in response to DHA supplementation in vivo but similar results were not evident in macrophages isolated from mice fed standard chow and supplemented with DHA in vitro. Co-culture of activated macrophages with MLE12 epithelial cells resulted in the release of high mobility group box 1 and leukotriene B4 from the epithelial cells and this release was attenuated by DHA supplementation. Collectively, our data indicate that long term supplementation with DHA as observed in vivo, resulted in deceased Notch 1/Jagged 1 protein expression however, DHA supplementation in vitro was sufficient to suppress release LTB4 and to protect epithelial cells in co-culture.

  8. Dexamethasone targeted directly to macrophages induces macrophage niches that promote erythroid expansion.

    PubMed

    Falchi, Mario; Varricchio, Lilian; Martelli, Fabrizio; Masiello, Francesca; Federici, Giulia; Zingariello, Maria; Girelli, Gabriella; Whitsett, Carolyn; Petricoin, Emanuel F; Moestrup, Søren Kragh; Zeuner, Ann; Migliaccio, Anna Rita

    2015-02-01

    Cultures of human CD34(pos) cells stimulated with erythroid growth factors plus dexamethasone, a model for stress erythropoiesis, generate numerous erythroid cells plus a few macrophages (approx. 3%; 3:1 positive and negative for CD169). Interactions occurring between erythroblasts and macrophages in these cultures and the biological effects associated with these interactions were documented by live phase-contrast videomicroscopy. Macrophages expressed high motility interacting with hundreds/thousands of erythroblasts per hour. CD169(pos) macrophages established multiple rapid 'loose' interactions with proerythroblasts leading to formation of transient erythroblastic island-like structures. By contrast, CD169(neg) macrophages established 'tight' interactions with mature erythroblasts and phagocytosed these cells. 'Loose' interactions of CD169(pos) macrophages were associated with proerythroblast cytokinesis (the M phase of the cell cycle) suggesting that these interactions may promote proerythroblast duplication. This hypothesis was tested by experiments that showed that as few as 103 macrophages significantly increased levels of 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide incorporation frequency in S/G2/M and cytokinesis expressed by proerythroblasts over 24 h of culture. These effects were observed also when macrophages were co-cultured with dexamethasone directly conjugated to a macrophage-specific CD163 antibody. In conclusion, in addition to promoting proerythroblast proliferation directly, dexamethasone stimulates expansion of these cells indirectly by stimulating maturation and cytokinesis supporting activity of macrophages. Copyright© Ferrata Storti Foundation.

  9. [Role of specialized care services of the national health service in the framework for the prevention of occupational risks (II)].

    PubMed

    Gallo-Fernández, M

    Since 1986, the Government of Navarra has taken over the functions of security and health as part of the health 'area', with a broad conception of health, avoiding separating the citizen from the worker. In 1993, the Instituto Navarro de Salud Laboral created, under the direction of the departments of Health and Labor, combined diverse functions and resources, integrating preexisting structures into a technical department to be responsible for the overall health care of workers. The structure is based on two coordinated pillars, security and hygiene at work and occupational health. As more specifically to do with health, we describe the systems of epidemiological information and vigilance and programs for occupational disabilities, health activities in industry and investigation of diseases. The Unidades de Salud Laboral link the workplace with the public health service. The occupational health plan of Navarra will set out future strategies. It is necessary to involve neurologists in occupational health. Occupational risks and injury are everyone's problem. The neurologist's role in accidents is usually of health care; detection of illness is more difficult when an occupational relationship is not considered. Data from work should be included in the clinical history. The official figures for occupational neurological diseases are ridiculous and more cases should be detected. There should be a fluid relationship between neurologists, occupational doctors and experts in prevention.

  10. Phagocytosis of Candida albicans Inhibits Autophagic Flux in Macrophages.

    PubMed

    Duan, Zhimin; Chen, Qing; Du, Leilei; Tong, Jianbo; Xu, Song; Zeng, Rong; Ma, Yuting; Chen, Xu; Li, Min

    2018-01-01

    Autophagy machinery has roles in the defense against microorganisms such as Candida albicans . Lipidated LC3, the marker protein of autophagy, participates in the elimination of C. albicans by forming a single-membrane phagosome; this process is called LC3-associated phagocytosis (LAP). However, the influence of C. albicans on autophagic flux is not clear. In this study, we found that C. albicans inhibited LC3 turnover in macrophages. After the phagocytosis of C. albicans in macrophages, we observed fewer acridine orange-positive vacuoles and RFP-GFP-LC3 puncta without colocalization with phagocytized C. albicans . However, phagocytosis of C. albicans led to LC3 recruitment, but p62 and ATG9A did not colocalize with LC3 or C. albicans . These effects are due to an MTOR-independent pathway. Nevertheless, we found that the C. albicans pattern-associated molecular pattern β -glucan increased LC3 turnover. In addition, phagocytosis of C. albicans caused a decrease in BrdU incorporation. Blocking autophagic flux aggravated this effect. Our findings suggest that phagocytosis of C. albicans decreases autophagic flux but induces LAP in an MTOR-independent manner in macrophages. Occupation of LC3 by recruiting engulfed C. albicans might contribute to the inhibition of autophagic flux. Our study highlights the coordinated machinery between canonical autophagy and LAP that defends against C. albicans challenge.

  11. Purinergic signaling during macrophage differentiation results in M2 alternative activated macrophages.

    PubMed

    Barberà-Cremades, Maria; Baroja-Mazo, Alberto; Pelegrín, Pablo

    2016-02-01

    Macrophages represent a highly heterogenic cell population of the innate immune system, with important roles in the initiation and resolution of the inflammatory response. Purinergic signaling regulates both M1 and M2 macrophage function at different levels by controlling the secretion of cytokines, phagocytosis, and the production of reactive oxygen species. We found that extracellular nucleotides arrest macrophage differentiation from bone marrow precursors via adenosine and P2 receptors. This results in a mature macrophage with increased expression of M2, but not M1, genes. Similar to adenosine and ATP, macrophage growth arrested with LPS treatment resulted in an increase of the M2-related marker Ym1. Recombinant Ym1 was able to affect macrophage proliferation and could, potentially, be involved in the arrest of macrophage growth during hematopoiesis. © Society for Leukocyte Biology.

  12. Interventions to prevent occupational noise-induced hearing loss: A Cochrane systematic review

    PubMed Central

    Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wouter A.; Mischke, Christina

    2015-01-01

    Objective To assess the effectiveness of interventions for preventing occupational noise exposure or hearing loss compared to no intervention or alternative interventions. Design We searched biomedical databases up to 25 January 2012 for randomized controlled trials (RCT), controlled before-after studies and interrupted time-series of hearing loss prevention among workers exposed to noise. Study sample We included 19 studies with 82 794 participants evaluating effects of hearing loss prevention programs (HLPP). The overall quality of studies was low to very low, as rated using the GRADE approach. Results One study of stricter legislation showed a favorable effect on noise levels. Three studies, of which two RCTs, did not find an effect of a HLPP. Four studies showed that better use of hearing protection devices in HLPPs decreased the risk of hearing loss. In four other studies, workers in a HLPP still had a 0.5 dB greater hearing loss at 4 kHz (95% CI – 0.5 to 1.7) than non-exposed workers. In two similar studies there was a substantial risk of hearing loss in spite of a HLPP. Conclusions Stricter enforcement of legislation and better implementation of HLPPs can reduce noise levels in workplaces. Better evaluations of technical interventions and long-term effects are needed. PMID:24564697

  13. Occupational cancer in Britain

    PubMed Central

    Chen, Yiqun; Osman, John

    2012-01-01

    Although only a relatively small proportion of cancer is attributable to occupational exposure to carcinogenic agents, the estimated number of deaths due to occupational cancer is high when compared to other deaths due to work-related ill health and injury. However, risk from occupational exposure to carcinogens can be minimised through proportionate but effective risk management. The Health and Safety Executive (HSE) is the regulator of workplace health and safety in Great Britain. As part of its aim to reduce ill health arising from failures to control properly exposure to hazards at work, HSE commissioned the research presented elsewhere in this supplement to enable it to identify priorities for preventing occupational cancer. The research has shown that occupational cancer remains a key health issue and that low-level exposure of a large number of workers to carcinogens is important. The finding that a small number of carcinogens have been responsible for the majority of the burden of occupational cancer provides key evidence in the development of priorities for significant reduction of occupational cancer. Although the research presented in this supplement reflects the consequences of past exposures to carcinogens, occupational cancer remains a problem. The potential for exposure to the agents considered in this research is still present in the workplace and the findings are relevant to prevention of future disease. In this article, the principle approaches for risk reduction are described. It provides supporting information on some of the initiatives already being undertaken, or those being put in place, to reduce occupational cancer in Great Britain. The need also for systematic collection of exposure information and the importance of raising awareness and changing behaviours are discussed. PMID:22710673

  14. SNAPIN is critical for lysosomal acidification and autophagosome maturation in macrophages

    PubMed Central

    Shi, Bo; Huang, Qi-Quan; Birkett, Robert; Doyle, Renee; Dorfleutner, Andrea; Stehlik, Christian; He, Congcong; Pope, Richard M.

    2017-01-01

    ABSTRACT We previously observed that SNAPIN, which is an adaptor protein in the SNARE core complex, was highly expressed in rheumatoid arthritis synovial tissue macrophages, but its role in macrophages and autoimmunity is unknown. To identify SNAPIN's role in these cells, we employed siRNA to silence the expression of SNAPIN in primary human macrophages. Silencing SNAPIN resulted in swollen lysosomes with impaired CTSD (cathepsin D) activation, although total CTSD was not reduced. Neither endosome cargo delivery nor lysosomal fusion with endosomes or autophagosomes was inhibited following the forced silencing of SNAPIN. The acidification of lysosomes and accumulation of autolysosomes in SNAPIN-silenced cells was inhibited, resulting in incomplete lysosomal hydrolysis and impaired macroautophagy/autophagy flux. Mechanistic studies employing ratiometric color fluorescence on living cells demonstrated that the reduction of SNAPIN resulted in a modest reduction of H+ pump activity; however, the more critical mechanism was a lysosomal proton leak. Overall, our results demonstrate that SNAPIN is critical in the maintenance of healthy lysosomes and autophagy through its role in lysosome acidification and autophagosome maturation in macrophages largely through preventing proton leak. These observations suggest an important role for SNAPIN and autophagy in the homeostasis of macrophages, particularly long-lived tissue resident macrophages. PMID:27929705

  15. [Noise-related occupational risk aboard fishing vessels: considerations on prevention and the protection of exposed workers].

    PubMed

    Rapisarda, V; Valentino, M; Bolognini, S; Fenga, C

    2004-01-01

    Recent legislation regarding the safety of workers aboard fishing vessels requires the appointment by ship owners of a Reference Physician in charge of health surveillance, preventive inspections and related tasks. As maritime workers, especially fishermen, have always been excluded from legal protection of occupational health, there are no exhaustive data on the incidence of their occupational disease. Several epidemiological studies of fishermen have evidenced a high prevalence and incidence of occupational conditions, among which noise-related hypoacousia. We report data of a phonometric survey conducted aboard six fishing vessels carrying a crew of less than six fishing in the mid-Adriatic. Measurements were performed during fishing and navigation aboard five vessels fitted with a fixed-pitch propeller and during fishing only aboard one vessel fitted with an controllable pitch propeller. Measurements were conducted: 1) in the engine rooms; 2) in the work area on deck; 3) at the winch; 4) in the wheelhouse; 5) in the mess-room and kitchen; 6) in the sleeping quarters. Results show that the equivalent sound pressure level in the engine rooms consistently exceeded 90 dBA on all vessels. The speed of the vessels fitted with the fixed-pitch propeller is 3-4 knots in the fishing phase and around 10 knots during navigation to and from the fishing grounds; noise emission is lower with the former regimen because of the smaller number of engine revolutions per minute. Our survey demonstrated considerably different noise levels in the various areas of vessels. One key element in workers' exposure, the tasks assigned and the environmental working conditions is of course the type of fishing in which the vessel is engaged. Further phonometric studies are required to assess the daily level of exposure per crew member, which represents the reference for the noise-related risk of each subject. Knowledge of the sound pressure levels in the work environment and the length of

  16. Macrophage Function in Early Dissemination and Dormancy of Breast Cancer

    DTIC Science & Technology

    2015-09-01

    decades after removal of the primary tumor, suggesting there is a window of opportunity to prevent their outgrowth. Additionally, the field of... prevent their outgrowth. Additionally, recent clinical data demonstrating that dissemination can occur much earlier than assumed and that patients...727-40. 7. Qian, B., et al., A distinct macrophage population mediates metastatic breast cancer cell extravasation , establishment and growth. PLoS One

  17. [Agricultural occupational health and social security].

    PubMed

    Lancry, Pierre-Jean; Crochet, Benoît; Richard-Hamelin, Géraldine; Grillet, Jean-Pierre

    2007-06-15

    The Mutualité Sociale Agricole (MSA) is the French social security agency for all agricultural wage earners and non-wage earners. It is the second French social security scheme after the general scheme, providing coverage for wage earners in commerce and industry. The MSA covers the whole spectrum of benefits (recovery, illness, family, retirement, occupational injury and disease) within a unique business window. The management of the MSA is overseen by elected representatives, thus creating a unique social democracy in the world of social security. Among the services managed by the MSA, occupational health and safety hold an original position: the MSA is indeed the only social security agency dealing with occupational health. 350 occupational physicians and 250 prevention consultants work in a multidisciplinary environment for the benefit of agricultural wage earners, as well as farmers, since the MSA implemented in 2002 an occupational risk prevention scheme for farmers.

  18. Occupational skin diseases and prevention among sanitation workers in China.

    PubMed

    Yan, Yuehua; Wang, Xinggang; Wu, Jianbo; Xu, Li

    2015-09-01

    Little research has been focused on the health status or the occupational protection awareness of sanitation workers. The policy recommendations on the occupational safety and health of sanitation workers based on the scientific research are also insufficient in developing countries like China. To study the incidence of dermatoses and the relevance with occupational exposure, protection awareness and protective measures among sanitation workers for better management and protection of the sanitation workers. 273 sanitation workers and 113 administrative staff from 11 streets of Wuhan were recruited. Dermatological problems were evaluated and recorded by physical examination. Occupational exposure, protection awareness, the use of protective equipments and personal history of skin disease were assessed by questionnaires. Compared with administrative staff, sanitation workers had much more occupational dermatological problems and had a much higher rate of harmful ultraviolet ray exposure. Young sanitation workers were more aware of occupational self-protection and a relatively higher rate of them using protective equipments compared with old ones. Exposure to multiple health hazards and the poor use of protective equipments are related to skin diseases in sanitation workers. Prejob training of self-protection and the use of protective equipments are recommended.

  19. [Medicolegal aspects of occupational dermatitis].

    PubMed

    Frimat, P; Fantoni-Quinton, S

    2009-01-01

    Occupational dermatitis is very common with considerable social and economic implications. Routine screening for occupational factors is essential since it may be necessary to introduce preventive measures and compensation could be due to the patient. The general practitioner may be assisted either by the occupational therapist or by specialised services to help the patient take the administrative steps necessary in order to identify a professional disease.

  20. LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

    PubMed

    van der Does, Anne M; Beekhuizen, Henry; Ravensbergen, Bep; Vos, Tim; Ottenhoff, Tom H M; van Dissel, Jaap T; Drijfhout, Jan W; Hiemstra, Pieter S; Nibbering, Peter H

    2010-08-01

    The human cathelicidin LL-37 has broad-spectrum antimicrobial activity. It also participates at the interface of innate and adaptive immunity by chemoattracting immune effector cells, modulating the production of a variety of inflammatory mediators by different cell types, and regulating the differentiation of monocytes into dendritic cells. In this study, we investigated the effects of LL-37 on the differentiation of human monocytes into anti-inflammatory macrophages (MPhi-2; driven by M-CSF) versus proinflammatory macrophages (MPhi-1; driven by GM-CSF) as well as on fully differentiated MPhi-1 and MPhi-2. Results revealed that monocytes cultured with M-CSF in the presence of LL-37 resulted in macrophages displaying a proinflammatory signature, namely, low expression of CD163 and little IL-10 and profound IL-12p40 production on LPS stimulation. The effects of LL-37 on M-CSF-driven macrophage differentiation were dose- and time-dependent with maximal effects observed at 10 microg/ml when the peptide was present from the start of the cultures. The peptide enhanced the GM-CSF-driven macrophage differentiation. Exposure of fully differentiated MPhi-2 to LL-37 for 6 d resulted in macrophages that produced less IL-10 and more IL-12p40 on LPS stimulation than control MPhi-2. In contrast, LL-37 had no effect on fully differentiated MPhi-1. Peptide mapping using a set of 16 overlapping 22-mer peptides covering the complete LL-37 sequence revealed that the C-terminal portion of LL-37 is responsible for directing macrophage differentiation. Our results furthermore indicate that the effects of LL-37 on macrophage differentiation required internalization of the peptide. Together, we conclude that LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

  1. Listing Occupational Carcinogens

    PubMed Central

    Siemiatycki, Jack; Richardson, Lesley; Straif, Kurt; Latreille, Benoit; Lakhani, Ramzan; Campbell, Sally; Rousseau, Marie-Claude; Boffetta, Paolo

    2004-01-01

    The occupational environment has been a most fruitful one for investigating the etiology of human cancer. Many recognized human carcinogens are occupational carcinogens. There is a large volume of epidemiologic and experimental data concerning cancer risks in different work environments. It is important to synthesize this information for both scientific and public health purposes. Various organizations and individuals have published lists of occupational carcinogens. However, such lists have been limited by unclear criteria for which recognized carcinogens should be considered occupational carcinogens, and by inconsistent and incomplete information on the occupations and industries in which the carcinogenic substances may be found and on their target sites of cancer. Based largely on the evaluations published by the International Agency for Research on Cancer, and augmented with additional information, the present article represents an attempt to summarize, in tabular form, current knowledge on occupational carcinogens, the occupations and industries in which they are found, and their target organs. We have considered 28 agents as definite occupational carcinogens, 27 agents as probable occupational carcinogens, and 113 agents as possible occupational carcinogens. These tables should be useful for regulatory or preventive purposes and for scientific purposes in research priority setting and in understanding carcinogenesis. PMID:15531427

  2. The cardiovascular macrophage: a missing link between gut microbiota and cardiovascular diseases?

    PubMed

    Chen, X; Zheng, L; Zheng, Y-Q; Yang, Q-G; Lin, Y; Ni, F-H; Li, Z-H

    2018-03-01

    The prevalence of cardiovascular diseases is on the rise. Interventions that would aid prevention or treatment of these diseases are essential. The microbes residing in the gut, collectively called "gut microbiota", produce a plethora of compounds that enter the bloodstream and affect the cardiovascular system. Signals ascending from gut microbiome are believed to modulate differentiation and functional activity of macrophages residing in perivascular tissue, atherosclerotic plaques, and perivascular areas of the brain. Cardiovascular macrophages may be the key players that transform the signals ascending from gut microbiome into increased predisposition to cardiovascular diseases. The present review summarizes the knowledge to date on potential relationships between gut microbiota, cardiovascular macrophages, and cardiovascular diseases.

  3. Macrophages under pressure: the role of macrophage polarization in hypertension.

    PubMed

    Harwani, Sailesh C

    2018-01-01

    Hypertension is a multifactorial disease involving the nervous, renal, and cardiovascular systems. Macrophages are the most abundant and ubiquitous immune cells, placing them in a unique position to serve as key mediators between these components. The polarization of macrophages confers vast phenotypic and functional plasticity, allowing them to act as proinflammatory, homeostatic, and anti-inflammatory agents. Key differences between the M1 and M2 phenotypes, the 2 subsets at the extremes of this polarization spectrum, place macrophages at a juncture to mediate many mechanisms involved in the pathogenesis of hypertension. Neuronal and non-neuronal regulation of the immune system, that is, the "neuroimmuno" axis, plays an integral role in the polarization of macrophages. In hypertension, the neuroimmuno axis results in synchronization of macrophage mobilization from immune cell reservoirs and their chemotaxis, via increased expression of chemoattractants, to end organs critical in the development of hypertension. This complicated system is largely coordinated by the dichotomous actions of the autonomic neuronal and non-neuronal activation of cholinergic, adrenergic, and neurohormonal receptors on macrophages, leading to their ability to "switch" between phenotypes at sites of active inflammation. Data from experimental models and human studies are in concordance with each other and support a central role for macrophage polarization in the pathogenesis of hypertension. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. [Life style and occupational factors and prevention of second primary cancers after childhood and adolescent cancer: Current state of knowledge].

    PubMed

    Duval, Sarah; Carretier, Julien; Boyle, Helen; Philip, Thierry; Berger, Claire; Marec-Bérard, Perrine; Fervers, Béatrice

    2015-01-01

    Survival of children, adolescents and young adults treated for cancer increased with improved treatments. But there is still an increased risk of second primary cancer (SPC) in the long term compared to the population of the same age, especially related to treatments. A reflection on the follow-up of this population and the prevention of SPC is an important issue. To perform a synthesis of the available literature on SCP risk factors, related risk behaviors, occupational exposures and prevention strategies. Literature search on PubMed from the following equation: "cancer [Tiab] AND young adult [Tiab] or teen [Tiab] or childhood [Tiab] AND prevention [Tiab] AND survivors [Mesh term]". Twenty-seven articles were included in this synthesis. Children, adolescents and young adults have similar risk behaviors than those of their peers regarding tobacco, diet and sun exposure; however, they have lower physical activity. There are few studies on prevention strategies focused on this population. Results of available studies remain inconclusive. No publication was found in relation to occupational exposure and risk of second cancer. Children, adolescents and young adults treated for cancer are a population at risk and require long-term follow-up and the implementation of effective prevention strategies tailored to this population. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  5. Inhibition of VDAC1 prevents Ca²⁺-mediated oxidative stress and apoptosis induced by 5-aminolevulinic acid mediated sonodynamic therapy in THP-1 macrophages.

    PubMed

    Chen, Haibo; Gao, Weiwei; Yang, Yang; Guo, Shuyuan; Wang, Huan; Wang, Wei; Zhang, Shuisheng; Zhou, Qi; Xu, Haobo; Yao, Jianting; Tian, Zhen; Li, Bicheng; Cao, Wenwu; Zhang, Zhiguo; Tian, Ye

    2014-12-01

    Ultrasound combined with endogenous protoporphyrin IX derived from 5-aminolevulinic acid (ALA-SDT) is known to induce apoptosis in multiple cancer cells and macrophages. Persistent retention of macrophages in the plaque has been implicated in the pathophysiology and progression of atherosclerosis. Here we investigated the effects of inhibition of voltage-dependent anion channel 1 (VDAC1) on ALA-SDT-induced THP-1 macrophages apoptosis. Cells were pre-treated with VDAC1 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) disodium salt for 1 h or downregulated VDAC1 expression by small interfering RNA and exposed to ultrasound. Cell viability was assessed by MTT assay, and cell apoptosis along with necrosis was evaluated by Hoechst 33342/propidium iodide staining and flow cytometry. Levels of cytochrome c release was assessed by confocal microscope and Western blot. The levels of full length caspases, caspase activation, and VDAC isoforms were analyzed by Western blot. Intracellular reactive oxygen species generation, mitochondrial membrane permeability, and intracellular Ca(2+) [Ca(2+)]i levels were measured with fluorescent probes. We confirmed that the pharmacological inhibition of VDAC1 by DIDS notably prevented ALA-SDT-induced cell apoptosis in THP-1 macrophages. Additionally, DIDS significantly inhibited intracellular ROS generation and apoptotic biochemical changes such as inner mitochondrial membrane permeabilization, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 and caspase-9. Moreover, ALA-SDT elevated the [Ca(2+)]i levels and it was also notably reduced by DIDS. Furthermore, both of intracellular ROS generation and cell apoptosis were predominately inhibited by Ca(2+) chelating reagent BAPTA-AM. Intriguingly, ALA-treatment markedly augmented VDAC1 protein levels exclusively, and the downregulation of VDAC1 expression by specific siRNA also significantly abolished cell apoptosis. Altogether, these

  6. Occupational Health

    MedlinePlus

    Occupational health problems occur at work or because of the kind of work you do. These problems can include ... by exposure to radiation Exposure to germs in health care settings Good job safety and prevention practices ...

  7. Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.

    PubMed

    Nishiwaki, Satoshi; Nakayama, Takayuki; Murata, Makoto; Nishida, Tetsuya; Terakura, Seitaro; Saito, Shigeki; Kato, Tomonori; Mizuno, Hiroki; Imahashi, Nobuhiko; Seto, Aika; Ozawa, Yukiyasu; Miyamura, Koichi; Ito, Masafumi; Takeshita, Kyosuke; Kato, Hidefumi; Toyokuni, Shinya; Nagao, Keisuke; Ueda, Ryuzo; Naoe, Tomoki

    2014-01-01

    Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.

  8. The response of macrophages to titanium particles is determined by macrophage polarization.

    PubMed

    Pajarinen, Jukka; Kouri, Vesa-Petteri; Jämsen, Eemeli; Li, Tian-Fang; Mandelin, Jami; Konttinen, Yrjö T

    2013-11-01

    Aseptic loosening of total joint replacements is driven by the reaction of macrophages to foreign body particles released from the implant. It was hypothesized that the macrophages' response to these particles is dependent, in addition to particle characteristics and contaminating biomolecules, on the state of macrophage polarization as determined by the local cytokine microenvironment. To test this hypothesis we differentiated M1 and M2 macrophages from human peripheral blood monocytes and compared their responses to titanium particles using genome-wide microarray analysis and a multiplex cytokine assay. In comparison to non-activated M0 macrophages, the overall chemotactic and inflammatory responses to titanium particles were greatly enhanced in M1 macrophages and effectively suppressed in M2 macrophages. In addition, the genome-wide approach revealed several novel, potentially osteolytic, particle-induced mediators, and signaling pathway analysis suggested the involvement of toll-like and nod-like receptor signaling in particle recognition. It is concluded that the magnitude of foreign body reaction caused by titanium particles is dependent on the state of macrophage polarization. Thus, by limiting the action of M1 polarizing factors, e.g. bacterial biofilm formation, in peri-implant tissues and promoting M2 macrophage polarization by biomaterial solutions or pharmacologically, it might be possible to restrict wear-particle-induced inflammation and osteolysis. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. [Informatics support for risk assessment and identification of preventive measures in small and micro-enterprises: occupational hazard datasheets].

    PubMed

    de Merich, D; Forte, Giulia

    2011-01-01

    Risk assessment is the fundamental process of an enterprise's prevention system and is the principal mandatory provision contained in the Health and Safety Law (Legislative Decree 81/2008) amended by Legislative Decree 106/2009. In order to properly comply with this obligation also in small-sized enterprises, the appropriate regulatory bodies should provide the enterprises with standardized tools and methods for identifying, assessing and managing risks. To assist in particular small and micro-enterprises (SMEs) with risk assessment, by providing a flexible tool that can also be standardized in the form of a datasheet, that can be updated with more detailed information on the various work contexts in Italy. Official efforts to provide Italian SMEs with information may initially make use of the findings of research conducted by ISPESL over the past 20 years, thanks in part to cooperation with other institutions (Regions, INAIL-National Insurance Institute for Occupational Accidents and Diseases), which have led to the creation of an information system on prevention consisting of numerous databases, both statistical and documental ("National System of Surveillance on fatal and serious accidents", "National System of Surveillance on work-related diseases", "Sector hazard profiles" database, "Solutions and Best Practices" database, "Technical Guidelines" database, "Training packages for prevention professionals in enterprises" database). With regard to evaluation criteria applicable within the enterprise, the possibility of combining traditional and uniform areas of assessment (by sector or by risk factor) with assessments by job/occupation has become possible thanks to the cooperation agreement made in 2009 by ISPESL, the ILO (International Labour Organisation) of Geneva and IIOSH (Israel Institute for Occupational Health and Hygiene) regarding the creation of an international Database (HDODB) based on risk datasheets per occupation. The project sets out to assist in

  10. Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway.

    PubMed

    Digiacomo, Graziana; Tusa, Ignazia; Bacci, Marina; Cipolleschi, Maria Grazia; Dello Sbarba, Persio; Rovida, Elisabetta

    2017-07-04

    Integrins, following binding to proteins of the extracellular matrix (ECM) including collagen, laminin and fibronectin (FN), are able to transduce molecular signals inside the cells and to regulate several biological functions such as migration, proliferation and differentiation. Besides activation of adaptor molecules and kinases, integrins transactivate Receptor Tyrosine Kinases (RTK). In particular, adhesion to the ECM may promote RTK activation in the absence of growth factors. The Colony-Stimulating Factor-1 Receptor (CSF-1R) is a RTK that supports the survival, proliferation, and motility of monocytes/macrophages, which are essential components of innate immunity and cancer development. Macrophage interaction with FN is recognized as an important aspect of host defense and wound repair. The aim of the present study was to investigate on a possible cross-talk between FN-elicited signals and CSF-1R in macrophages. FN induced migration in BAC1.2F5 and J774 murine macrophage cell lines and in human primary macrophages. Adhesion to FN determined phosphorylation of the Focal Adhesion Kinase (FAK) and Src Family Kinases (SFK) and activation of the SFK/FAK complex, as witnessed by paxillin phosphorylation. SFK activity was necessary for FAK activation and macrophage migration. Moreover, FN-induced migration was dependent on FAK in either murine macrophage cell lines or human primary macrophages. FN also induced FAK-dependent/ligand-independent CSF-1R phosphorylation, as well as the interaction between CSF-1R and β1. CSF-1R activity was necessary for FN-induced macrophage migration. Indeed, genetic or pharmacological inhibition of CSF-1R prevented FN-induced macrophage migration. Our results identified a new SFK-FAK/CSF-1R signaling pathway that mediates FN-induced migration of macrophages.

  11. Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway.

    PubMed

    Lin, Wen; Wu, Rachel T; Wu, Tienyuan; Khor, Tin-Oo; Wang, Hu; Kong, Ah-Ng

    2008-10-15

    Sulforaphane (SFN) is a natural isothiocyanate that is present in cruciferous vegetables such as broccoli and cabbage. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents, which is related in part to its potent anti-inflammation properties. In the present study, we compared the anti-inflammatory effect of SFN on LPS-stimulated inflammation in primary peritoneal macrophages derived from Nrf2 (+/+) and Nrf2 (-/-) mice. Pretreatment of SFN in Nrf2 (+/+) primary peritoneal macrophages potently inhibited LPS-stimulated mRNA expression, protein expression and production of TNF-alpha, IL-1beta, COX-2 and iNOS. HO-1 expression was significantly augmented in LPS-stimulated Nrf2 (+/+) primary peritoneal macrophages by SFN. Interestingly, the anti-inflammatory effect was attenuated in Nrf2 (-/-) primary peritoneal macrophages. We concluded that SFN exerts its anti-inflammatory activity mainly via activation of Nrf2 in mouse peritoneal macrophages.

  12. Leucine supplementation attenuates macrophage foam-cell formation: Studies in humans, mice, and cultured macrophages.

    PubMed

    Grajeda-Iglesias, Claudia; Rom, Oren; Hamoud, Shadi; Volkova, Nina; Hayek, Tony; Abu-Saleh, Niroz; Aviram, Michael

    2018-02-05

    Whereas atherogenicity of dietary lipids has been largely studied, relatively little is known about the possible contribution of dietary amino acids to macrophage foam-cell formation, a hallmark of early atherogenesis. Recently, we showed that leucine has antiatherogenic properties in the macrophage model system. In this study, an in-depth investigation of the role of leucine in macrophage lipid metabolism was conducted by supplementing humans, mice, or cultured macrophages with leucine. Macrophage incubation with serum obtained from healthy adults supplemented with leucine (5 g/d, 3 weeks) significantly decreased cellular cholesterol mass by inhibiting the rate of cholesterol biosynthesis and increasing cholesterol efflux from macrophages. Similarly, leucine supplementation to C57BL/6 mice (8 weeks) resulted in decreased cholesterol content in their harvested peritoneal macrophages (MPM) in relation with reduced cholesterol biosynthesis rate. Studies in J774A.1 murine macrophages revealed that leucine dose-dependently decreased cellular cholesterol and triglyceride mass. Macrophages treated with leucine (0.2 mM) showed attenuated uptake of very low-density lipoproteins and triglyceride biosynthesis rate, with a concurrent down-regulation of diacylglycerol acyltransferase-1, a key enzyme catalyzing triglyceride biosynthesis in macrophages. Similar effects were observed when macrophages were treated with α-ketoisocaproate, a key leucine metabolite. Finally, both in vivo and in vitro leucine supplementation significantly improved macrophage mitochondrial respiration and ATP production. The above studies, conducted in human, mice, and cultured macrophages, highlight a protective role for leucine attenuating macrophage foam-cell formation by mechanisms related to the metabolism of cholesterol, triglycerides, and energy production. © 2018 BioFactors, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  13. Innate NK cells and macrophages recognize and reject allogeneic nonself in vivo via different mechanisms.

    PubMed

    Liu, Wentao; Xiao, Xiang; Demirci, Gulcin; Madsen, Joren; Li, Xian C

    2012-03-15

    Both innate and adaptive immune cells are involved in the allograft response. But how the innate immune cells respond to allotransplants remains poorly defined. In the current study, we examined the roles of NK cells and macrophages in recognizing and rejecting allogeneic cells in vivo. We found that in naive mice NK cells are the primary effector cells in the killing of allogeneic cells via "missing self" recognition. However, in alloantigen-presensitized mice, NK cells are dispensable. Instead, macrophages become alloreactive and readily recognize and reject allogeneic nonself. This effect requires help from activated CD4(+) T cells and involves CD40/CD40L engagement, because blocking CD40/CD40L interactions prevents macrophage-mediated rejection of allogeneic cells. Conversely, actively stimulating CD40 triggers macrophage-mediated rejection in the absence of CD4(+) T cells. Importantly, alloantigen-primed and CD4(+) T cell-helped macrophages (licensed macrophages) exhibit potent regulatory function in vivo in an acute graft-versus-host disease model. Together, our data uncover an important role for macrophages in the alloimmune response and may have important clinical implications.

  14. [Occupational diseases in an airline company].

    PubMed

    Lie, A

    1998-06-30

    617 cases of occupational health disorders in an average population of approximately 4,400 were reported by the Occupational Health Services of the Norwegian section of SAS during the period 1985 to 1996. Musculoskeletal disorders accounted for approximately 75% of all registered disorders. Wherever possible, occupational disorders should be registered and preventive measures initiated by the company. It is therefore of great importance that a registration system should include all occupational disorders. If we compare our figures with the official Norwegian figures from the Labour Inspectorate, we may conclude that only 3-4% of occupational disorders are reported to the Authorities. In particular it seems that many disorders which do not yield economic compensation (musculoskeletal disorders, and mental stress and burnout syndromes) are not reported at all, making it less likely that preventive measures are implemented. The Nordic figures indicate that inadequate reporting occurs more frequently in Norway than in Sweden, Denmark and Finland.

  15. Inhibition of differentiation of monocyte to macrophages in atherosclerosis by oligomeric proanthocyanidins -In-vivo and in-vitro study.

    PubMed

    Mohana, Thiruchenduran; Navin, Alukkathara Vijayan; Jamuna, Sanker; Sakeena Sadullah, Mohammed Sadullah; Niranjali Devaraj, Sivasithamparam

    2015-08-01

    Monocyte to macrophage differentiation is a key event in the progression of atherosclerosis. An understanding on the fundamental molecular mechanisms and the identification of regulatory mechanisms behind this differentiation may aid in the identification of new therapeutic strategies. Inhibition of this phenomenon will form first line of defense in the prevention and treatment of atherosclerosis. In the current study we explored hypercholesterolemia induced monocyte to macrophage differentiation in-vivo (Wistar rats) leading to atherosclerosis and OxyLDL, M-CSF induced monocyte differentiation in-vitro (U937 cells). Oligomeric proanthocyanidin (OPC) isolated from Crataegus oxyacantha was tested for its efficacy in downregulating this differentiation and in preventing atherogenic disturbances. Cholesterol cholic acid diet induced an increased monocyte to macrophage differentiation by upregulating MCP1 and VCAM1 which induced the inflammatory cytokines that further substantiated the monocyte conversion and infiltration into the vascular walls. On addition of OxyLDL and M-CSF to U937 cells, macrophage markers CD36 and CD 68, PPARγ, MMP2 and 9 were elevated, suggesting differentiation. OPC downregulated this differentiation and thus could prevent the initiation of atherosclerosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Long non-coding RNA cox-2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization.

    PubMed

    Ye, Yibiao; Xu, Yunxiuxiu; Lai, Yu; He, Wenguang; Li, Yanshan; Wang, Ruomei; Luo, Xinxi; Chen, Rufu; Chen, Tao

    2018-03-01

    Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. We investigate long non-coding RNA (lncRNA) cox-2 in macrophage polarization and the regulatory mechanism functions in hepatocellular carcinoma (HCC). Lipopolysaccharide (LPS) was used to induce RAW264.7 macrophages into M1 type, and IL-4 was to induce RAW264.7 macrophages into M2 type. We selected mouse hepatic cell line Hepal-6 and hepatoma cell line HepG2 for co-incubation with M1 or M2 macrophages. Quantitative real-time PCR was used to detect the expressions of lncRNA cox-2 and mRNAs. ELISA was conducted for testing IL-12 and IL-10 expressions; Western blotting for epithelial mesenchymal transition related factors (E-cadherin and Vimentin). An MTT, colony formation assay, flow cytometry, transwell assay, and stretch test were conducted to test cell abilities. The M1 macrophages had higher lncRNA cox-2 expression than that in the non-polarized macrophages and M2 macrophages. The lncRNA cox-2 siRNA decreased the expression levels of IL-12, iNOS, and TNF-α in M1 macrophages, increased the expression levels of IL-10, Arg-1, and Fizz-1 in M2 macrophages (all P < 0.05). The lncRNA cox-2 siRNA reduces the ability of M1 macrophages to inhibit HCC cell proliferation, invasion, migration, EMT, angiogenesis and facilitate apoptosis while strengthening the ability of M2 macrophages to promote proliferation HCC cell growth and inhibit apoptosis. These findings indicate that lncRNA cox-2 inhibits HCC immune evasion and tumor growth by inhibiting the polarization of M2 macrophages. © 2017 Wiley Periodicals, Inc.

  17. 78 FR 64504 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-29

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH or..., Number 177, Pages 56235-56236. Contact Person for More Information: Price Connor, Ph.D., NIOSH Health...

  18. [Occupational injury, a public health priority].

    PubMed

    Benavides, Fernando G; Delclos, Jordi; Benach, Joan; Serra, Consol

    2006-01-01

    The aim of this review is to stimulate new ideas and actions for the prevention of this important public health problem. In 2002 and 2003, respectively, the number of non-fatal occupational injuries was 971,406 and 906,638. Thus, every day in Spain there are more than 2500 non-fatal and between 2 and 3 fatal occupational injuries. Although the profile of the at-risk worker population has changed greatly over the past decade, both quantitatively and qualitatively, the risk of occupational injury still centers on blue collar workers, whether qualified or nonqualified, in the primary and secondary sectors of economic activity. The most common mechanisms of occupational injuries are overexertion for non-fatal injuries and traffic-related for fatal events. The adverse health consequences of new types of employment, which emphasize flexibility and deregulation of the labour market, are exemplified by the association between temporary employment and increased risk of occupational injury. New injury prevention programs have emerged in the last decade, but they appear to have had limited impact. Preventive activities should focus both on working conditions at the company level (micro) as well as on employment and industrial public policies (macro). Greater evaluation is needed of these latter policies.

  19. Fatalities from occupational diseases in Connecticut.

    PubMed

    Morse, T; Storey, E

    1999-08-01

    Occupational diseases in Connecticut were identified using reports to the Workers' Compensation Commission, Connecticut OSHA, Vital Statistics, and the Tumor Registry. There were 93 identified fatalities from occupational disease in 1995, and 90 in 1994, approximately three times the number of traumatic occupational fatalities. Identified fatalities were predominantly from asbestos-related diseases, including mesothelioma and asbestosis. Most occupational diseases are not readily identifiable with current reporting mechanisms. Based on national estimates, these figures are considered to be an underestimate of the true burden of occupational disease. Increased awareness and reporting of occupational diseases is needed to properly identify and prevent these common conditions.

  20. Peculiar macrophagous adaptations in a new Cretaceous pliosaurid

    PubMed Central

    Arkhangelsky, Maxim S.; Stenshin, Ilya M.; Uspensky, Gleb N.; Zverkov, Nikolay G.

    2015-01-01

    During the Middle and Late Jurassic, pliosaurid plesiosaurs evolved gigantic body size and a series of craniodental adaptations that have been linked to the occupation of an apex predator niche. Cretaceous pliosaurids (i.e. Brachaucheninae) depart from this morphology, being slightly smaller and lacking the macrophagous adaptations seen in earlier forms. However, the fossil record of Early Cretaceous pliosaurids is poor, concealing the evolution and ecological diversity of the group. Here, we report a new pliosaurid from the Late Hauterivian (Early Cretaceous) of Russia. Phylogenetic analyses using reduced consensus methods recover it as the basalmost brachauchenine. This pliosaurid is smaller than other derived pliosaurids, has tooth alveoli clustered in pairs and possesses trihedral teeth with complex serrated carinae. Maximum-likelihood ancestral state reconstruction suggests early brachauchenines retained trihedral teeth from their ancestors, but modified this feature in a unique way, convergent with macrophagous archosaurs or sphenacodontoids. Our findings indicate that Early Cretaceous marine reptile teeth with serrated carinae cannot be unequivocally assigned to metriorhynchoid crocodylomorphs. Furthermore, they extend the known diversity of dental adaptations seen in Sauropterygia, the longest lived clade of marine tetrapods. PMID:27019740

  1. Macrophage-Specific Expression of IL-37 in Hyperlipidemic Mice Attenuates Atherosclerosis.

    PubMed

    McCurdy, Sara; Baumer, Yvonne; Toulmin, Emma; Lee, Bog-Hieu; Boisvert, William A

    2017-11-15

    Atherosclerosis, the progressive buildup of plaque within arterial blood vessels, can lead to fatal downstream events, such as heart attack or stroke. A key event contributing to the development of atherosclerosis is the infiltration of monocytes and its associated inflammation, as well as the formation of lipid-laden macrophage foam cells within the vessel wall. IL-37 is recognized as an important anti-inflammatory cytokine expressed especially by immune cells. This study was undertaken to elucidate the role of macrophage-expressed IL-37 in reducing the production and effects of proinflammatory cytokines, preventing foam cell formation, and reducing the development of atherosclerosis. Expression of human IL-37 was achieved with a macrophage-specific overexpression system, using the CD68 promoter in mouse primary bone marrow-derived macrophages via retroviral transduction. Macrophage IL-37 expression in vitro resulted in decreased mRNA (e.g., IL-1B, IL-6, and IL-12) and secreted protein production (e.g., IL-6, M-CSF, and ICAM-1) of key inflammatory mediators. IL-37 expression also inhibited macrophage proliferation, apoptosis, and transmigration, as well as reduced lipid uptake, compared with controls in vitro. The in vivo effects of macrophage-expressed IL-37 were investigated through bone marrow transplantation of transduced hematopoietic stem cells into irradiated atherosclerosis-prone Ldlr -/- mice. After 10 wk on a high-fat/high-cholesterol diet, mice with IL-37-expressing macrophages showed reduced disease pathogenesis, which was demonstrated by significantly less arterial plaque development and systemic inflammation compared with control mice. The athero-protective effect of macrophage-expressed IL-37 has implications for development of future therapies to treat atherosclerosis, as well as other chronic inflammatory diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

  2. [Macrophage activation in atherosclerosis. Message 1: Activation of macrophages normally and in atherosclerotic lesions].

    PubMed

    Nikiforov, N G; Kornienko, V Y; Karagodin, V P; Orekhov, A N

    2015-01-01

    Macrophages play important role in initiation and progression of inflammation in atherosclerosis. Plaque macrophages were shown to exhibit a phenotypic range that is intermediate between two extremes, M1 (proinflammatory) and M2 (anti-inflammatory). Indeed, in atherosclerosis, macrophages demonstrate phenotypic plasticity to rapidly adjust to changing microenvironmental conditions. In plaque macrophages demonstrate different phenotypes, and besides macrophage phenotypes could be changed. Phenotypes M1, M2, M4, Mhem, HA-mac, M(Hb) u Mox are described in the article. Ability of macrophages change their phenotype also considered.

  3. Ethanol increases matrix metalloproteinase-12 expression via NADPH oxidase-dependent ROS production in macrophages

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Mi Jin; Nepal, Saroj; Lee, Eung-Seok

    2013-11-15

    Matrix metalloproteinase-12 (MMP-12), an enzyme responsible for degradation of extracellular matrix, plays an important role in the progression of various diseases, including inflammation and fibrosis. Although most of those are pathogenic conditions induced by ethanol ingestion, the effect of ethanol on MMP-12 has not been explored. In the present study, we investigated the effect of ethanol on MMP-12 expression and its potential mechanisms in macrophages. Here, we demonstrated that ethanol treatment increased MMP-12 expression in primary murine peritoneal macrophages and RAW 264.7 macrophages at both mRNA and protein levels. Ethanol treatment also significantly increased the activity of nicotinamide adenine dinucleotidemore » (NADPH) oxidase and the expression of NADPH oxidase-2 (Nox2). Pretreatment with an anti-oxidant (N-acetyl cysteine) or a selective inhibitor of NADPH oxidase (diphenyleneiodonium chloride (DPI)) prevented ethanol-induced MMP-12 expression. Furthermore, knockdown of Nox2 by small interfering RNA (siRNA) prevented ethanol-induced ROS production and MMP-12 expression in RAW 264.7 macrophages, indicating a critical role for Nox2 in ethanol-induced intracellular ROS production and MMP-12 expression in macrophages. We also showed that ethanol-induced Nox2 expression was suppressed by transient transfection with dominant negative IκB-α plasmid or pretreatment with Bay 11-7082, a selective inhibitor of NF-κB, in RAW 264.7 macrophages. In addition, ethanol-induced Nox2 expression was also attenuated by treatment with a selective inhibitor of p38 MAPK, suggesting involvement of p38 MAPK/NF-κB pathway in ethanol-induced Nox2 expression. Taken together, these results demonstrate that ethanol treatment elicited increase in MMP-12 expression via increase in ROS production derived from Nox2 in macrophages. - Highlights: • Ethanol increases ROS production through up-regulation of Nox2 in macrophages. • Enhanced oxidative stress contributes to

  4. Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention.

    PubMed

    Quinn, Margaret M; Henneberger, Paul K; Braun, Barbara; Delclos, George L; Fagan, Kathleen; Huang, Vanthida; Knaack, Jennifer L S; Kusek, Linda; Lee, Soo-Jeong; Le Moual, Nicole; Maher, Kathryn A E; McCrone, Susan H; Mitchell, Amber Hogan; Pechter, Elise; Rosenman, Kenneth; Sehulster, Lynne; Stephens, Alicia C; Wilburn, Susan; Zock, Jan-Paul

    2015-05-01

    The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

  5. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    PubMed

    Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald

    2013-01-01

    Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

  6. Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi anemia macrophages.

    PubMed

    Garbati, Michael R; Hays, Laura E; Rathbun, R Keaney; Jillette, Nathaniel; Chin, Kathy; Al-Dhalimy, Muhsen; Agarwal, Anupriya; Newell, Amy E Hanlon; Olson, Susan B; Bagby, Grover C

    2016-03-01

    The Fanconi anemia proteins participate in a canonical pathway that repairs cross-linking agent-induced DNA damage. Cells with inactivated Fanconi anemia genes are universally hypersensitive to such agents. Fanconi anemia-deficient hematopoietic stem cells are also hypersensitive to inflammatory cytokines, and, as importantly, Fanconi anemia macrophages overproduce such cytokines in response to TLR4 and TLR7/8 agonists. We questioned whether TLR-induced DNA damage is the primary cause of aberrantly regulated cytokine production in Fanconi anemia macrophages by quantifying TLR agonist-induced TNF-α production, DNA strand breaks, crosslinker-induced chromosomal breakage, and Fanconi anemia core complex function in Fanconi anemia complementation group C-deficient human and murine macrophages. Although both M1 and M2 polarized Fanconi anemia cells were predictably hypersensitive to mitomycin C, only M1 macrophages overproduced TNF-α in response to TLR-activating signals. DNA damaging agents alone did not induce TNF-α production in the absence of TLR agonists in wild-type or Fanconi anemia macrophages, and mitomycin C did not enhance TLR responses in either normal or Fanconi anemia cells. TLR4 and TLR7/8 activation induced cytokine overproduction in Fanconi anemia macrophages. Also, although TLR4 activation was associated with induced double strand breaks, TLR7/8 activation was not. That DNA strand breaks and chromosome breaks are neither necessary nor sufficient to account for the overproduction of inflammatory cytokines by Fanconi anemia cells suggests that noncanonical anti-inflammatory functions of Fanconi anemia complementation group C contribute to the aberrant macrophage phenotype and suggests that suppression of macrophage/TLR hyperreactivity might prevent cytokine-induced stem cell attrition in Fanconi anemia. © Society for Leukocyte Biology.

  7. Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway

    PubMed Central

    Lin, Wen; Wu, Rachel T; Wu, Tienyuan; Khor, Tin-Oo; Wang, Hu; Kong, Ah-Ng

    2008-01-01

    Sulforaphane (SFN) is a natural isothiocyanate that is present in cruciferous vegetables such as broccoli and cabbage. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents, which is related in part to its potent anti-inflammation properties. In the present study, we compared the anti-inflammatory effect of SFN on LPS-stimulated inflammation in primary peritoneal macrophages derived from Nrf2 (+/+) and Nrf2 mice. Pretreatment of SFN in Nrf2 (+/+) primary peritoneal macrophages potently inhibited LPS-stimulated mRNA expression, protein expression and production of TNFα, IL-1β, Cox-2 and iNOS. HO-1 expression, which is significantly augmented in LPS-stimulated Nrf2 (+/+) primary peritoneal macrophages by SFN. Interestingly, the anti-inflammatory effect was attenuated in Nrf2 (−/−) primary peritoneal macrophages. We concluded that SFN exerts its anti-inflammatory activity mainly via activation of Nrf2 in mouse peritoneal macrophages. PMID:18755157

  8. Immobilized heavy chain-hyaluronic acid polarizes lipopolysaccharide-activated macrophages toward M2 phenotype.

    PubMed

    He, Hua; Zhang, Suzhen; Tighe, Sean; Son, Ji; Tseng, Scheffer C G

    2013-09-06

    Despite the known anti-inflammatory effect of amniotic membrane, its action mechanism remains largely unknown. HC-HA complex (HC-HA) purified from human amniotic membrane consists of high molecular weight hyaluronic acid (HA) covalently linked to the heavy chain (HC) 1 of inter-α-trypsin inhibitor. In this study, we show that soluble HC-HA also contained pentraxin 3 and induced the apoptosis of both formyl-Met-Leu-Phe or LPS-activated neutrophils and LPS-activated macrophages while not affecting the resting cells. This enhanced apoptosis was caused by the inhibition of cell adhesion, spreading, and proliferation caused by HC-HA binding of LPS-activated macrophages and preventing adhesion to the plastic surface. Preferentially, soluble HC-HA promoted phagocytosis of apoptotic neutrophils in resting macrophages, whereas immobilized HC-HA promoted phagocytosis in LPS-activated macrophages. Upon concomitant LPS stimulation, immobilized HC-HA but not HA polarized macrophages toward the M2 phenotype by down-regulating IRF5 protein and preventing its nuclear localization and by down-regulating IL-12, TNF-α, and NO synthase 2. Additionally, IL-10, TGF-β1, peroxisome proliferator-activated receptor γ, LIGHT (TNF superfamily 14), and sphingosine kinase-1 were up-regulated, and such M2 polarization was dependent on TLR ligation. Collectively, these data suggest that HC-HA is a unique matrix component different from HA and uses multiple mechanisms to suppress M1 while promoting M2 phenotype. This anti-inflammatory action of HC-HA is highly desirable to promote wound healing in diseases heightened by unsuccessful transition from M1 to M2 phenotypes.

  9. [Macrophages in human semen].

    PubMed

    Bouvet, Beatriz Reina; Brufman, Adriana Silvia; Paparella, Cecilia Vicenta; Feldman, Rodolfo Nestor; Gatti, Vanda Nora; Solis, Edita Amalia

    2003-11-01

    To investigate the presence of macrophages in human semen samples and the function they carry out in the seminal fluid. Their presence was studied in relation to spermatic morphology, percentage of spermatozoids with native DNA, and presence of antispermatic antibodies. The work was performed with semen samples from 31 unfertile males from 63 couples in which the "female factor" was ruled out as the cause of infertility. Sperm study according to WHO (1992) was carried out in all samples, in addition to: DNA study with acridine orange as fluorocrom, macrophage concentration by neutral red in a Neubauer camera, and detection of antispermatic antibodies with a mixed agglutination test (TAC II) (validated with Mar Screen-Fertility technologies). Sperm morphology was evaluated by Papanicolaou test. 19/31 selected sperm samples (61.3%) showed increased concentration of macrophages, 13 of them (41.9%) with denaturalized DNA, and 8 (25.8%) abnormal morphology. Six samples showed increased macrophage concentration and predominance of native DNA, whereas 11 samples showed increased macrophages and abnormal morphology. Among 18 (58.1%) samples showing antispermatic antibodies 14 (77.7%) had an increased concentration of macrophages. Statistical analysis resulted in a high correlation between macrophage concentration and increased percentage of spermatozoids with denaturalized DNA (p < 0.05). An increased concentration of macrophages is associated with the presence of antispermatic antibodies (p < 0.05). There was not evidence of significant association between concentration of macrophages and percentage of morphologically normal spermatozoids (p < 0.05). We can conclude that macrophages are present in human semen and participate in immunovigilance contributing to improve the seminal quality.

  10. Viral Infection of Human Lung Macrophages Increases PDL1 Expression via IFNβ

    PubMed Central

    Staples, Karl J.; Nicholas, Ben; McKendry, Richard T.; Spalluto, C. Mirella; Wallington, Joshua C.; Bragg, Craig W.; Robinson, Emily C.; Martin, Kirstin; Djukanović, Ratko; Wilkinson, Tom M. A.

    2015-01-01

    Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM) and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production. PMID:25775126

  11. Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

    PubMed

    Staples, Karl J; Nicholas, Ben; McKendry, Richard T; Spalluto, C Mirella; Wallington, Joshua C; Bragg, Craig W; Robinson, Emily C; Martin, Kirstin; Djukanović, Ratko; Wilkinson, Tom M A

    2015-01-01

    Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM) and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

  12. Changing pattern of the subcellular distribution of erythroblast macrophage protein (Emp) during macrophage differentiation.

    PubMed

    Soni, Shivani; Bala, Shashi; Kumar, Ajay; Hanspal, Manjit

    2007-01-01

    Erythroblast macrophage protein (Emp) mediates the attachment of erythroid cells to macrophages and is required for normal differentiation of both cell lineages. In erythroid cells, Emp is believed to be involved in nuclear extrusion, however, its role in macrophage differentiation is unknown. Information on the changes in the expression level and subcellular distribution of Emp in differentiating macrophages is essential for understanding the function of Emp. Macrophages of varying maturity were examined by immunofluorescence microscopy and biochemical methods. Our data show that Emp is expressed in all stages of maturation, but its localization pattern changes dramatically during maturation: in immature macrophages, a substantial fraction of Emp is associated with the nuclear matrix, whereas in more mature cells, Emp is expressed largely at cell surface. Pulse-chase experiments show that nascent Emp migrates intracellularly from the cytoplasm to the plasma membrane more efficiently in mature macrophages than in immature cells. Incubation of erythroid cells with macrophages in culture shows that erythroid cells attach to mature macrophages but not to immature macrophage precursors. Together, our data show that the temporal and spatial expression of Emp correlates with its role in erythroblastic island formation and suggest that Emp may be involved in multiple cellular functions.

  13. *CHANGING PATTERN OF THE SUBCELLULAR DISTRIBUTION OF ERYTHROBLAST MACROPHAGE PROTEIN (EMP) DURING MACROPHAGE DIFFERENTIATION

    PubMed Central

    Soni, Shivani; Bala, Shashi; Kumar, Ajay; Hanspal, Manjit

    2007-01-01

    Erythroblast macrophage protein (Emp), mediates the attachment of erythroid cells to macrophages, and is required for normal differentiation of both cell lineages. In erythroid cells Emp is believed to be involved in nuclear extrusion however, its role in macrophage differentiation is unknown. Information on the changes in the expression level and subcellular distribution of Emp in differentiating macrophages is essential for understanding the function of Emp. Macrophages of varying maturity were examined by immunofluorescence microscopy and biochemical methods. Our data shows that Emp is expressed in all stages of maturation, but its localization pattern changes dramatically during maturation: in immature macrophages, a substantial fraction of Emp is associated with the nuclear matrix, whereas in more mature cells, Emp is expressed largely at cell surface. Pulse-chase experiments show that nascent Emp migrates intracellularly from the cytoplasm to the plasma membrane more efficiently in mature macrophages than in immature cells. Incubation of erythroid cells with macrophages in culture show that erythroid cells attach to mature macrophages but not to immature macrophage precursors. Together, our data shows that the temporal and spatial expression of Emp correlates with its role in erythroblastic island formation, and suggests that Emp may be involved in multiple cellular functions. PMID:17071116

  14. Opportunities and obstacles in translating evidence to policy in occupational asthma.

    PubMed

    Tarlo, Susan M; Arif, Ahmed A; Delclos, George L; Henneberger, Paul; Patel, Jenil

    2018-06-01

    Occupational asthma (OA), a common respiratory disorder in Western countries, is caused by exposures at the workplace. It is part of a broader definition of work-related asthma (WRA) that also includes pre-existing asthma aggravated by substances present in the workplace environment, and it is potentially preventable. The purpose of this paper is to illustrate preventive measures for occupational asthma by case studies. In three case studies we discuss preventive measures that have been associated with reductions in incidence of occupational asthma from natural rubber latex and from diisocyanates as supported by published literature. We also discuss challenges in relation to asthma from cleaning products in healthcare work. Several preventive measures have been associated with reduction in incidence of occupational asthma from natural rubber latex and from diisocyanates, and may provide lessons for prevention of other causes of occupational asthma. Cleaning products remain an unresolved problem at present with respect to asthma risks but potential measures include the use of safer products and safer applications such as avoidance of spray products, use of occupational hygiene methods such as improving local ventilation, and when appropriate, the use of personal protective devices. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Opportunities and obstacles in translating evidence to policy in occupational asthma

    PubMed Central

    Tarlo, Susan M.; Arif, Ahmed A.; Delclos, George L.; Henneberger, Paul; Patel, Jenil

    2018-01-01

    Purpose Occupational asthma (OA), a common respiratory disorder in Western countries, is caused by exposures at the workplace. It is part of a broader definition of work-related asthma (WRA) that also includes pre-existing asthma aggravated by substances present in the workplace environment, and it is potentially preventable. The purpose of this paper is to illustrate preventive measures for occupational asthma by case studies. Methods In three case studies we discuss preventive measures that have been associated with reductions in incidence of occupational asthma from natural rubber latex and from diisocyanates as supported by published literature. We also discuss challenges in relation to asthma from cleaning products in healthcare work. Results and conclusions Several preventive measures have been associated with reduction in incidence of occupational asthma from natural rubber latex and from diisocyanates, and may provide lessons for prevention of other causes of occupational asthma. Cleaning products remain an unresolved problem at present with respect to asthma risks but potential measures include the use of safer products and safer applications such as avoidance of spray products, use of occupational hygiene methods such as improving local ventilation, and when appropriate, the use of personal protective devices. PMID:28434545

  16. Classical and alternative macrophages have impaired function during acute and chronic HIV-1 infection.

    PubMed

    Galvão-Lima, Leonardo J; Espíndola, Milena S; Soares, Luana S; Zambuzi, Fabiana A; Cacemiro, Maira; Fontanari, Caroline; Bollela, Valdes R; Frantz, Fabiani G

    Three decades after HIV recognition and its association with AIDS development, many advances have emerged - especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (M GM-CSF+IFN-γ ) or alternative (M IL-4+IL13 ) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Our therapy protocols were not effective in restoring the functional alterations induced

  17. Macrophages Exhibit a Large Repertoire of Activation States via Multiple Mechanisms of Macrophage-activating Factors.

    PubMed

    Sumiya, Y U; Inoue, Takahiro; Ishikawa, Mami; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

    2016-07-01

    Macrophages are important components of human defense systems and consequently key to antitumor immunity. Human-serum macrophage activation factor (serum MAF) can activate macrophages, making it a promising reagent for anticancer therapy. We established four different macrophage subtypes through introduction of different culture conditions to THP-1- and U937-derived macrophages. We assessed phagocytic activity to understand subtype responses to typical macrophage activation factors (MAFs) and the activation mechanisms of serum MAF. All four macrophage subtypes differed in their response to all MAFs. Moreover, serum MAF had two different activation mechanisms: N-acetylgalactosamine (GalNAc)-dependent and GalNAc-independent. Macrophage activation states and mechanisms are heterogeneous. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Occupational Health Update: Focus on Preventing the Acquisition of Infections with Pre-exposure Prophylaxis and Postexposure Prophylaxis.

    PubMed

    Weber, David J; Rutala, William A

    2016-09-01

    Health care personnel are commonly exposed to infectious agents via sharp injuries (eg, human immunodeficiency virus, hepatitis B virus, and hepatitis C virus), direct patient care (eg, pertussis and meningococcus), and the contaminated environment (eg, Clostridium difficile). An effective occupational program is a key aspect of preventing acquisition of an infection by offering the following: (1) education of health care personnel regarding proper handling of sharps, early identification and isolation of potentially infectious patients, and hand hygiene; (2) assuring immunity to vaccine-preventable diseases; and, (3) immediate availability of a medical evaluation after a nonprotected exposure to an infectious disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cell Elasticity Determines Macrophage Function

    PubMed Central

    Patel, Naimish R.; Bole, Medhavi; Chen, Cheng; Hardin, Charles C.; Kho, Alvin T.; Mih, Justin; Deng, Linhong; Butler, James; Tschumperlin, Daniel; Fredberg, Jeffrey J.; Krishnan, Ramaswamy; Koziel, Henry

    2012-01-01

    Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function. PMID:23028423

  20. Mycobacteria, Metals, and the Macrophage

    PubMed Central

    Niederweis, Michael; Wolschendorf, Frank; Mitra, Avishek; Neyrolles, Olivier

    2015-01-01

    Summary Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi-faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal-targeted approaches might complement existing TB chemotherapeutic regimens with novel anti-infective therapies. PMID:25703564

  1. Inhibition of Neddylation Represses Lipopolysaccharide-induced Proinflammatory Cytokine Production in Macrophage Cells

    PubMed Central

    Chang, Fang-Mei; Reyna, Sara M.; Granados, Jose C.; Wei, Sung-Jen; Innis-Whitehouse, Wendy; Maffi, Shivani K.; Rodriguez, Edward; Slaga, Thomas J.; Short, John D.

    2012-01-01

    Cullin-RING E3 ligases (CRLs) are a class of ubiquitin ligases that control the proteasomal degradation of numerous target proteins, including IκB, and the activity of these CRLs are positively regulated by conjugation of a Nedd8 polypeptide onto Cullin proteins in a process called neddylation. CRL-mediated degradation of IκB, which normally interacts with and retains NF-κB in the cytoplasm, permits nuclear translocation and transactivation of the NF-κB transcription factor. Neddylation occurs through a multistep enzymatic process involving Nedd8 activating enzymes, and recent studies have shown that the pharmacological agent, MLN4924, can potently inhibit Nedd8 activating enzymes, thereby preventing neddylation of Cullin proteins and preventing the degradation of CRL target proteins. In macrophages, regulation of NF-κB signaling functions as a primary pathway by which infectious agents such as lipopolysaccharides (LPSs) cause the up-regulation of proinflammatory cytokines. Here we have analyzed the effects of MLN4924, and compared the effects of MLN4924 with a known anti-inflammatory agent (dexamethasone), on certain proinflammatory cytokines (TNF-α and IL-6) and the NF-κB signaling pathway in LPS-stimulated macrophages. We also used siRNA to block neddylation to assess the role of this molecular process during LPS-induced cytokine responsiveness. Our results demonstrate that blocking neddylation, either pharmacologically or using siRNA, abrogates the increase in certain proinflammatory cytokines secreted from macrophages in response to LPS. In addition, we have shown that MLN4924 and dexamethasone inhibit LPS-induced cytokine up-regulation at the transcriptional level, albeit through different molecular mechanisms. Thus, neddylation represents a novel molecular process in macrophages that can be targeted to prevent and/or treat the LPS-induced up-regulation of proinflammatory cytokines and the disease processes associated with their up-regulation. PMID

  2. Regulation of the macrophage oxytocin receptor in response to inflammation

    PubMed Central

    Szeto, Angela; Sun-Suslow, Ni; Mendez, Armando J.; Hernandez, Rosa I.; Wagner, Klaus V.

    2017-01-01

    It has been demonstrated that the neuropeptide oxytocin (OT) attenuates oxidative stress and inflammation in macrophages. In the current study, we examined the role of inflammation on the expression of the oxytocin receptor (OXTR). We hypothesized that OXTR expression is increased during the inflammation through a nuclear factor-κB (NF-κB)-mediated pathway, thus responding as an acute-phase protein. Inflammation was induced by treating macrophages (human primary, THP-1, and murine) with lipopolysaccharide (LPS) and monitored by expression of IL-6. Expression of OXTR and vasopressin receptors was assessed by qPCR, and OXTR expression was confirmed by immunoblotting. Inflammation upregulated OXTR transcription 10- to 250-fold relative to control in THP-1 and human primary macrophages and increased OXTR protein expression. In contrast, vasopressin receptor-2 mRNA expression was reduced following LPS treatment. Blocking NF-κB activation prevented the increase in OXTR transcription. OT treatment of control cells and LPS-treated cells increased ERK1/2 phosphorylation, demonstrating activation of the OXTR/Gαq/11 signaling pathway. OT activation of OXTR reduced secretion of IL-6 in LPS-activated macrophages. Collectively, these findings suggest that OXTR is an acute-phase protein and that its increased expression is regulated by NF-κB and functions to attenuate cellular inflammatory responses in macrophages. PMID:28049625

  3. Proprotein convertase 1/3 inhibited macrophages: A novel therapeutic based on drone macrophages.

    PubMed

    Duhamel, Marie; Rodet, Franck; Murgoci, Adriana; Wisztorski, Maxence; Day, Robert; Fournier, Isabelle; Salzet, Michel

    2016-06-01

    We demonstrated here thanks to proteomic, that proprotein convertase 1/3 knockdown macrophages present all the characteristic of activated pro-inflammatory macrophages. TLR4 and TLR9 signaling pathways can be enhanced leading to the secretion of pro-inflammatory factors and antitumor factors. We can control their activation by controlling one enzyme, PC1/3. In a tumor context, PC1/3 inhibition in macrophages may reactivate them and lead to a cytokine storm after stimulation "at distance" with a TLR ligand. Therefore, we name these proprotein convertase inhibited macrophages the "drone macrophages". They constitute an innovative cell therapy to treat efficiently tumors.

  4. Early Macrophage Recruitment and Alternative Activation Are Critical for the Later Development of Hypoxia-induced Pulmonary Hypertension

    PubMed Central

    Vergadi, Eleni; Chang, Mun Seog; Lee, Changjin; Liang, Olin; Liu, Xianlan; Fernandez-Gonzalez, Angeles; Mitsialis, S. Alex; Kourembanas, Stella

    2011-01-01

    Background Lung inflammation precedes the development of hypoxia-induced pulmonary hypertension (HPH); however its role in the pathogenesis of HPH is poorly understood. We sought to characterize the hypoxic inflammatory response and elucidate its role in the development of HPH. We also aimed to investigate the mechanisms by which heme oxygenase-1 (HO-1), an anti-inflammatory enzyme, is protective in HPH. Methods and Results We generated bitransgenic mice that overexpress human HO-1 under doxycycline (dox) control in an inducible, lung-specific manner. Hypoxic exposure of mice in the absence of dox resulted in early transient accumulation of monocytes/macrophages in the bronchoalveolar lavage. Alveolar macrophages acquired an alternatively activated phenotype (M2) in response to hypoxia, characterized by the expression of Found in Inflammatory Zone-1, Arginase-1 and Chitinase-3-like-3. A brief, two-day pulse of dox delayed but did not prevent the peak of hypoxic inflammation, and could not protect from HPH. In contrast, a seven-day dox treatment sustained high HO-1 levels during the entire period of hypoxic inflammation, inhibited macrophage accumulation and activation, induced macrophage IL-10 expression, and prevented the development of HPH. Supernatants from hypoxic M2 macrophages promoted proliferation of pulmonary artery smooth muscle cells while treatment with carbon monoxide, a HO-1 enzymatic product, abrogated this effect. Conclusions Early recruitment and alternative activation of macrophages in hypoxic lungs is critical for the later development of HPH. HO-1 may confer protection from HPH by effectively modifing macrophage activation state in hypoxia. PMID:21518986

  5. Occupational injuries in Italy.

    PubMed

    Baldasseroni, Alberto; Chellini, Elisabetta; Mantero, Silvia; Giovannetti, Lucia

    2005-01-01

    Data collected by the Italian Funds for Occupational Injuries and Diseases (INAIL) on incidence and mortality for occupational injuries in Italy during 1951-2001 are described with respect to the two main occupational sectors, Industry and Services, and Agriculture. Comparisons with other EU countries are included to place the current severe phenomenon in context. An ad hoc analysis aimed at verifying the completeness of the data on occupational fatal accidents collected by INAIL in Tuscany is reported: a linkage between the INAIL data and those registered by the Tuscan Regional Mortality Registry highlights that a number of working areas are not covered by INAIL, a problem whose solution would be useful for primary prevention.

  6. Invasive breast carcinoma cells from patients exhibit MenaINV- and macrophage-dependent transendothelial migration

    PubMed Central

    Pignatelli, Jeanine; Goswami, Sumanta; Jones, Joan G.; Rohan, Thomas E.; Pieri, Evan; Chen, Xiaoming; Adler, Esther; Cox, Dianne; Maleki, Sara; Bresnick, Anne; Gertler, Frank B.; Condeelis, John S.; Oktay, Maja H.

    2014-01-01

    Metastasis is a complex, multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epidermal growth factor (EGF)–responsive cell migration protein] are present with macrophages at sites of intravasation, called TMEM sites (for tumor microenvironment of metastasis), in patient tumor samples. Furthermore, the density of these intravasation sites correlates with metastatic risk in patients. We found that intravasation of breast cancer cells may be prevented by blocking the signaling between cancer cells and macrophages. We obtained invasive breast ductal carcinoma cells of various subtypes by fine-needle aspiration (FNA) biopsies from patients and found that, in an in vitro transendothelial migration assay, cells that migrated through a layer of human endothelial cells were enriched for the transcript encoding MenaINV, an invasive isoform of Mena. This enhanced transendothelial migration required macrophages and occurred with all of the breast cancer subtypes. Using mouse macrophages and the human cancer cells from the FNAs, we identified paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R). The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down MenaINV or adding an antibody that blocks CSF-1R function prevented transendothelial migration. Our findings indicate that MenaINV and TMEM frequency are correlated prognostic markers and CSF-1 and MenaINV may be therapeutic targets to prevent metastasis of multiple breast cancer subtypes. PMID:25429076

  7. Biomaterial adherent macrophage apoptosis is increased by hydrophilic and anionic substrates in vivo

    NASA Astrophysics Data System (ADS)

    Brodbeck, William G.; Patel, Jasmine; Voskerician, Gabriela; Christenson, Elizabeth; Shive, Matthew S.; Nakayama, Yasuhide; Matsuda, Takehisa; Ziats, Nicholas P.; Anderson, James M.

    2002-08-01

    An in vivo rat cage implant system was used to identify potential surface chemistries that prevent failure of implanted biomedical devices and prostheses by limiting monocyte adhesion and macrophage fusion into foreign-body giant cells while inducing adherent-macrophage apoptosis. Hydrophobic, hydrophilic, anionic, and cationic surfaces were used for implantation. Analysis of the exudate surrounding the materials revealed no differences between surfaces in the types or levels of cells present. Conversely, the proportion of adherent cells undergoing apoptosis was increased significantly on anionic and hydrophilic surfaces (46 ± 3.7 and 57 ± 5.0%, respectively) when compared with the polyethylene terephthalate base surface. Additionally, hydrophilic and anionic substrates provided decreased rates of monocyte/macrophage adhesion and fusion. These studies demonstrate that biomaterial-adherent cells undergo material-dependent apoptosis in vivo, rendering potentially harmful macrophages nonfunctional while the surrounding environment of the implant remains unaffected.

  8. [Need for occupational and environmental allergology in occupational health - the 45th Japanese society of Occupational and Environmental Allergy Annual Meeting 2014 in Fukuoka].

    PubMed

    Kishikawa, Reiko; Oshikawa, Chie

    2014-12-01

    The 45th Japanese Society of Occupational and Environmental Allergy (OEA) Annual Meeting 2014 was held in Fukuoka city in conjunction with a technical course for occupational health physicians to learn occupational and environmental diseases more deeply. Allergic reaction due to low concentrations of chemical and biological materials is important in toxicological diseases due to highly concentrated chemical materials in the field of occupational and environmental medicine. In this paper we describe the activities of the OEA, which was established in 1970 and has completely cured patients with severe occupational asthma, such as the regional Konjac asthma in Gunma prefecture and Sea Squirt asthma in Hiroshima prefecture. Regard for the occupational environment will prevent the onset and/or exacerbation of allergic occupational disease in individual employees with allergy. Occupational cancer of the bile duct and asbestosis are also current, serious issues that should be resolved as soon as possible. It is desirable for the occupational health physician to have a large stock of knowledge about toxicological and allergic diseases in various occupational settings to maintain the health and safety of workers.

  9. Soybean-derived Bowman-Birk inhibitor (BBI) blocks HIV entry into macrophages.

    PubMed

    Ma, Tong-Cui; Le Guo; Zhou, Run-Hong; Wang, Xu; Liu, Jin-Biao; Li, Jie-Liang; Zhou, Yu; Hou, Wei; Ho, Wen-Zhe

    2018-01-01

    Bowman-Birk inhibitor (BBI) is a soybean-derived protease inhibitor that has anti-inflammation and anti-HIV effect. Here, we further investigated the anti-HIV action of BBI in macrophages, focusing on its effect on viral entry. We found that BBI could significantly block HIV entry into macrophages. Investigation of the mechanism(s) of the BBI action on HIV inhibition showed that BBI down-regulated the expression of CD4 receptor (as much as 80%) and induced the production of the CC chemokines (up to 60 folds at protein level) in macrophages. This inhibitory effect of BBI on HIV entry could be blocked by the neutralization antibodies to CC chemokines. These findings indicate that BBI may have therapeutic potential as a viral entry inhibitor for the prevention and treatment of HIV infection. Copyright © 2017. Published by Elsevier Inc.

  10. Candida albicans Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions

    PubMed Central

    MacCallum, Donna M.; Brown, Gordon D.

    2017-01-01

    ABSTRACT   The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid l-arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host’s arginase activity to prevent the conversion of l-arginine to nitric oxide. We report here that C. albicans blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the C. albicans-induced arginase activity with the arginase-specific substrate inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that C. albicans influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore, C. albicans modulates l-arginine metabolism in macrophages during an infection, potentiating its own survival. PMID:28119468

  11. Occupational injuries in Canadian youth: an analysis of 22 years of surveillance data collected from the Canadian Hospitals Injury Reporting and Prevention Program

    PubMed Central

    Pratt, B.; Cheesman, J.; Breslin, C.; Do, M. T.

    2016-01-01

    Abstract Introduction: Inexperience, inadequate training and differential hazard exposure may contribute to a higher risk of injury in young workers. This study describes features of work-related injuries in young Canadians to identify areas for potential occupational injury prevention strategies. Methods: We analyzed records for youth aged 10–17 presenting to Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) emergency departments (EDs) from 1991–2012. We classified work-related injuries into job groups corresponding to National Occupational Classification for Statistics 2006 codes and conducted descriptive analyses to assess injury profiles by job group. Age- and sex-adjusted proportionate injury ratios (PIRs) and 95% confidence intervals (CIs) were calculated to compare the nature of injuries between occupational and non-occupational events overall and by job group. Results: Of the 6046 injuries (0.72% of events in this age group) that occurred during work, 63.9% were among males. Youth in food and beverage occupations (54.6% males) made up 35.4% of work-related ED visits and 10.2% of work-related hospital admissions, while primary industry workers (76.4% males) made up 4.8% of work-related ED visits and 24.6% of work-related hospital admissions. PIRs were significantly elevated for burns (9.77, 95% CI: 8.94–10.67), crushing/amputations (6.72, 95% CI: 5.79–7.80), electrical injuries (6.04, 95% CI: 3.64–10.00), bites (5.09, 95% CI: 4.47–5.79), open wounds (2.68, 95% CI: 2.59–2.78) and eye injuries (2.50, 95% CI: 2.20–2.83) in occupational versus non-occupational events. These were largely driven by high proportional incidence of injury types unique to job groups. Conclusion: Our findings provide occupation group-specific information on common injury types that can be used to support targeted approaches to reduce incidence of youth injury in the workplace. PMID:27172126

  12. Isolation and Differentiation of Murine Macrophages.

    PubMed

    Rios, Francisco J; Touyz, Rhian M; Montezano, Augusto C

    2017-01-01

    Macrophages play a major role in inflammation, wound healing, and tissue repair. Infiltrated monocytes differentiate into different macrophage subtypes with protective or pathogenic activities in vascular lesions. In the heart and vascular tissues, pathological activation promotes cardiovascular inflammation and remodeling and there is increasing evidence that macrophages play important mechanisms in this environment. Primary murine macrophages can be obtained from: bone marrow by different treatments (granulocyte-macrophage colony-stimulating factor-GM-CSF, macrophage colony-stimulating factor-M-CSF or supernatant of murine fibroblast L929), peritoneal cavity (resident or thioglycolate elicit macrophages), from the lung (alveolar macrophages) or from adipose tissue. In this chapter we describe some protocols to obtain primary murine macrophages and how to identify a pure macrophage population or activation phenotypes using different markers.

  13. Development of the Final Version of the Classification and Assessment of Occupational Dysfunction Scale

    PubMed Central

    Teraoka, Mutsumi; Kyougoku, Makoto

    2015-01-01

    Occupational therapy is involved in disability prevention and health enhancement through the prevention of occupational dysfunction. Although many occupational dysfunction scales exist, no standard method is available for the assessment and classification of occupational dysfunction, which may include occupational imbalance, occupational deprivation, occupational alienation, and occupational marginalization. The purpose of this study was to develop the final version of Classification and Assessment of Occupational Dysfunction (CAOD). Our study demonstrated the validity and reliability of CAOD in a group of undergraduate students. The CAOD scale includes 16 items and addresses the following 4 domains: occupational imbalance, occupational deprivation, occupational alienation, and occupational marginalization. PMID:26263375

  14. Probiotic Bacillus amyloliquefaciens mediate M1 macrophage polarization in mouse bone marrow-derived macrophages.

    PubMed

    Ji, Jian; Hu, Sheng-Lan; Cui, Zhi-Wen; Li, Wei-Fen

    2013-05-01

    Depending on the microenvironment, macrophages can acquire distinct functional phenotypes, referred to as classically activated M1 and M2. M1 macrophages are considered potent effector cells that kill intracellular pathogens, and M2 macrophages promote the resolution of wound healing. In this study, we are interested to know whether probiotic Bacillus amyloliquefaciens (Ba) can induce macrophages polarization. Real-time fluorescence PCR analysis demonstrated that the expression of IL-1β, iNOS, TNF-α and IL-6 genes for M1 macrophages was significantly increased at 1.5 h after probiotic Ba treatment compared to the probiotic Ba-free treatment (P < 0.01), whereas the expression of M2 macrophage marker genes (Arg1, Fizz1, MR, Ym1) was decreased (P < 0.05). Furthermore, the phagocytic activity was dramatically increased in the Ba-treated BMDMs using a FITC-dextran endocytosis assay. Together, these findings indicated that probiotic Ba facilitated polarization of M1 macrophages and enhanced its phagocytic capacity. The results expanded our knowledge about probiotic function-involved macrophage polarization.

  15. Alternatively activated macrophages (M2 macrophages) in the skin of patient with localized scleroderma.

    PubMed

    Higashi-Kuwata, Nobuyo; Makino, Takamitsu; Inoue, Yuji; Takeya, Motohiro; Ihn, Hironobu

    2009-08-01

    Localized scleroderma is a connective tissue disorder that is limited to the skin and subcutaneous tissue. Macrophages have been reported to be particularly activated in patients with skin disease including systemic sclerosis and are potentially important sources for fibrosis-inducing cytokines, such as transforming growth factor beta. To clarify the features of immunohistochemical characterization of the immune cell infiltrates in localized scleroderma focusing on macrophages, skin biopsy specimens were analysed by immunohistochemistry. The number of cells stained with monoclonal antibodies, CD68, CD163 and CD204, was calculated. An evident macrophage infiltrate and increased number of alternatively activated macrophages (M2 macrophages) in their fibrotic areas were observed along with their severity of inflammation. This study revealed that alternatively activated macrophages (M2 macrophages) may be a potential source of fibrosis-inducing cytokines in localized scleroderma, and may play a crucial role in the pathogenesis of localized scleroderma.

  16. Eliminating Legionella by inhibiting BCL-XL to induce macrophage apoptosis.

    PubMed

    Speir, Mary; Lawlor, Kate E; Glaser, Stefan P; Abraham, Gilu; Chow, Seong; Vogrin, Adam; Schulze, Keith E; Schuelein, Ralf; O'Reilly, Lorraine A; Mason, Kylie; Hartland, Elizabeth L; Lithgow, Trevor; Strasser, Andreas; Lessene, Guillaume; Huang, David C S; Vince, James E; Naderer, Thomas

    2016-02-24

    Human pathogenic Legionella replicate in alveolar macrophages and cause a potentially lethal form of pneumonia known as Legionnaires' disease(1). Here, we have identified a host-directed therapeutic approach to eliminate intracellular Legionella infections. We demonstrate that the genetic deletion, or pharmacological inhibition, of the host cell pro-survival protein BCL-XL induces intrinsic apoptosis of macrophages infected with virulent Legionella strains, thereby abrogating Legionella replication. BCL-XL is essential for the survival of Legionella-infected macrophages due to bacterial inhibition of host-cell protein synthesis, resulting in reduced levels of the short-lived, related BCL-2 pro-survival family member, MCL-1. Consequently, a single dose of a BCL-XL-targeted BH3-mimetic therapy, or myeloid cell-restricted deletion of BCL-XL, limits Legionella replication and prevents lethal lung infections in mice. These results indicate that repurposing BH3-mimetic compounds, originally developed to induce cancer cell apoptosis, may have efficacy in treating Legionnaires' and other diseases caused by intracellular microbes.

  17. Occupational pressure-targeting organisational factors to ameliorate occupational dysfunction.

    PubMed

    Loh, Siew Yim; Than, Winn; Quek, Kia Fatt

    2011-12-01

    Chronic pressure at work has debilitating impact on healthcare employers (e.g. reduced productivity, high costs, poor patient care) and on female healthcare employees (e.g. sickness, dysfunction). This paper highlights relationship at work as the key occupational source of work-stress which is organisational in nature. A cross-sectional study (n = 230) was conducted using the Pressure Management Inventory on several female dominated health professions within a large public hospital. Analysis of variance was used to show relationship between sources and outcome of pressure. Linear regressions were used to predict which sources of pressure (IV) was linked to the outcomes of occupational pressure (DV). The number one source of occupational pressure is relationships at work (i.e. with supervisors), and not workload. 'Relationship' is also the key predictor of several negative outcomes of pressure at work. Analysis of variance showed significant differences in two sources of pressures, i.e. Workload (P = 0.04) and Home-work balance (P = 0.03). This paper provides insights into the occupational pressure of women health professionals by highlighting the organisational sources of pressure and the implications for preventing occupational dysfunction secondary to stress at work.

  18. Preventing Protein Adsorption and Macrophage Uptake of Gold Nanoparticles via a Hydrophobic Shield

    PubMed Central

    Larson, Timothy A.; Joshi, Pratixa P.; Sokolov, Konstantin

    2012-01-01

    Polyethylene glycol (PEG) surface coatings are widely used to render stealth properties to nanoparticles in biological applications. There is abundant literature on benefits of PEG coatings and their ability to reduce protein adsorption, to diminish non-specific interactions with cells, and to improve pharmacokinetics, but very little discussion of the limitations of PEG coatings. Here, we show that physiological concentrations of cysteine and cystine can displace methoxy-PEG-thiol molecules from the gold nanoparticle (GNP) surface that leads to protein adsorption and cell uptake in macrophages within 24 hours. Furthermore, we address this problem by incorporating an alkyl linker between the PEG and the thiol moieties that provides a hydrophobic shield layer between the gold surface and the hydrophilic outer PEG layer. The mPEG-alkyl-thiol coating greatly reduces protein adsorption on GNPs and their macrophage uptake. This has important implications for the design of GNP for biological systems. PMID:23009596

  19. [An analysis of eligibility for occupational health inspection agencies in eight provinces of China].

    PubMed

    Qi, Fang; Wang, Huanqiang; Li, Tao; Lyu, Xiangpei; Zhu, Qiuhong; Yu, Chen

    2015-06-01

    To investigate the eligibility and main problems for occupational health inspection agencies in China, and to provide technical references for improvement of occupational health inspection. A survey was performed in occupational health inspection agencies that obtained eligibility before June 2011 in eight provinces: Zhejiang, Jiangsu, Shandong, Hubei, Guangxi, Shanghai, Chongqing, and Shenzhen. The survey used the General Information Questionnaire for Occupational Health Inspection Agency made by the project of Occupational Health Surveillance and Diagnosis and Identification of Occupational Diseases in China and Australia. A total of 650 agencies obtained eligibility for occupational health inspection in the eight provinces. These agencies contained 343 centers of disease control and prevention (CDC) or health and epidemic prevention stations (52.8%), 219 hospitals (33.7%), 25 institutes or centers for occupational disease prevention and control (3.8%), 29 community health service centers (4.5%), and 34 other agencies (5.2%) including departments of preventive and health care and preventive medicine outpatient departments. Four hundred and fifty-three agencies completed the questionnaire survey with a response rate of 69.7%. The main types of eligible agencies were different among various regions. A majority of occupational health inspection agencies were hospitals in Shanghai and Zhejiang (67.1%, 62.3%), departments of preventive and health care in Shenzhen (70.0%), and CDCs in Chongqing, Jiangsu, Hubei, and Guangxi. Each agency obtained 3.5 occupational health inspection eligibilities on average. Most of agencies could perform eligible health inspection for dust, harmful physical factors, or harmful chemical factors (84.8%, 87.9%, 87.2%). Moreover, 72.8% of agencies were eligible for all the three types of inspections. A few agencies were able to perform eligible health inspection for harmful biological factors or radiation work (22.5%, 23.0%). An occupational

  20. Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis.

    PubMed

    Pirdel, Leila; Pirdel, Manijeh

    2014-06-01

    This article presents an overview of the involvement of iron overload-induced nitric oxide (NO) overproduction in apoptosis of peritoneal macrophages of women with endometriosis. We have postulated that the peritoneal iron overload originated from retrograde menstruation or bleeding lesions in the ectopic endometrium, which may contribute to the development of endometriosis by a wide range of mechanisms, including oxidative damage and chronic inflammation. Excessive NO production may also be associated with impaired clearance of endometrial cells by macrophages, which promotes cell growth in the peritoneal cavity. Therefore, further research of the mechanisms and consequences of macrophage apoptosis in endometriosis helps discover novel therapeutic strategies that are designed to prevent progression of endometriosis. © 2014 Society for Reproduction and Fertility.

  1. Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-α Pathway

    PubMed Central

    Kim, Joo Young; Sohn, Jung Ho; Choi, Je-Min; Lee, Jae-Hyun; Hong, Chein-Soo; Lee, Joo-Shil; Park, Jung-Won

    2012-01-01

    The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-α. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-α production by alveolar macrophages through the PAR-2 pathway and whether the TNF-α production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-α production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-α. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-α production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-α blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-α level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-α dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model. PMID:23094102

  2. Adipocyte-Macrophage Cross-Talk in Obesity.

    PubMed

    Engin, Ayse Basak

    2017-01-01

    Obesity is characterized by the chronic low-grade activation of the innate immune system. In this respect, macrophage-elicited metabolic inflammation and adipocyte-macrophage interaction has a primary importance in obesity. Large amounts of macrophages are accumulated by different mechanisms in obese adipose tissue. Hypertrophic adipocyte-derived chemotactic monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) pathway also promotes more macrophage accumulation into the obese adipose tissue. However, increased local extracellular lipid concentrations is a final mechanism for adipose tissue macrophage accumulation. A paracrine loop involving free fatty acids and tumor necrosis factor-alpha (TNF-alpha) between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue. Adipocyte-specific caspase-1 and production of interleukin-1beta (IL-1beta) by macrophages; both adipocyte and macrophage induction by toll like receptor-4 (TLR4) through nuclear factor-kappaB (NF-kappaB) activation; free fatty acid-induced and TLR-mediated activation of c-Jun N-terminal kinase (JNK)-related pro-inflammatory pathways in CD11c+ immune cells; are effective in macrophage accumulation and in the development of adipose tissue inflammation. Old adipocytes are removed by macrophages through trogocytosis or sending an "eat me" signal. The obesity-induced changes in adipose tissue macrophage numbers are mainly due to increases in the triple-positive CD11b+ F4/80+ CD11c+ adipose tissue macrophage subpopulation. The ratio of M1-to-M2 macrophages is increased in obesity. Furthermore, hypoxia along with higher concentrations of free fatty acids exacerbates macrophage-mediated inflammation in obesity. The metabolic status of adipocytes is a major determinant of macrophage inflammatory output. Macrophage/adipocyte fatty-acid-binding proteins act at the interface of metabolic and inflammatory pathways. Both macrophages and

  3. CXCL4 downregulates the atheroprotective hemoglobin receptor CD163 in human macrophages.

    PubMed

    Gleissner, Christian A; Shaked, Iftach; Erbel, Christian; Böckler, Dittmar; Katus, Hugo A; Ley, Klaus

    2010-01-08

    CXCL4 is a platelet-derived chemokine that promotes macrophage differentiation from monocytes. Deletion of the PF4 gene that encodes CXCL4 reduces atherosclerotic lesions in ApoE(-/-) mice. We sought to study effects of CXCL4 on macrophage differentiation with possible relevance for atherogenesis. Flow cytometry for expression of surface markers in macrophage colony-stimulating factor (M-CSF)- and CXCL4-induced macrophages demonstrated virtually complete absence of the hemoglobin scavenger receptor CD163 in CXCL4-induced macrophages. mRNA for CD163 was downregulated as early as 2 hours after CXCL4. CD163 protein reached a minimum after 3 days, which was not reversed by treatment of cells with M-CSF. The CXCL4 effect was entirely neutralized by heparin, which bound CXCL4 and prevented CXCL4 surface binding to monocytes. Pretreatment of cells with chlorate, which inhibits glycosaminoglycan synthesis, strongly inhibited CXCL4-dependent downregulation of CD163. Similar to recombinant CXCL4, releasate from human platelets also reduced CD163 expression. CXCL4-differentiated macrophages were unable to upregulate the atheroprotective enzyme heme oxygenase-1 at the RNA and protein level in response to hemoglobin-haptoglobin complexes. Immunofluorescence of human atherosclerotic plaques demonstrated presence of both CD68+CD163+ and CD68+CD163- macrophages. PF4 and CD163 gene expression within human atherosclerotic lesions were inversely correlated, supporting the in vivo relevance of CXCL4-induced downregulation of CD163. CXCL4 may promote atherogenesis by suppressing CD163 in macrophages, which are then unable to upregulate the atheroprotective enzyme heme oxygenase-1 in response to hemoglobin.

  4. CXCL4 Downregulates the Atheroprotective Hemoglobin Receptor CD163 in Human Macrophages

    PubMed Central

    Gleissner, Christian A.; Shaked, Iftach; Erbel, Christian; Böckler, Dittmar; Katus, Hugo A.; Ley, Klaus

    2010-01-01

    Rationale CXCL4 is a platelet-derived chemokine that promotes macrophage differentiation from monocytes. Deletion of the PF4 gene that encodes CXCL4 reduces atherosclerotic lesions in ApoE−/− mice. Objective We sought to study effects of CXCL4 on macrophage differentiation with possible relevance for atherogenesis. Methods and Results Flow cytometry for expression of surface markers in macrophage colony–stimulating factor (M-CSF)– and CXCL4-induced macrophages demonstrated virtually complete absence of the hemoglobin scavenger receptor CD163 in CXCL4-induced macrophages. mRNA for CD163 was downregulated as early as 2 hours after CXCL4. CD163 protein reached a minimum after 3 days, which was not reversed by treatment of cells with M-CSF. The CXCL4 effect was entirely neutralized by heparin, which bound CXCL4 and prevented CXCL4 surface binding to monocytes. Pretreatment of cells with chlorate, which inhibits glycosaminoglycan synthesis, strongly inhibited CXCL4-dependent downregulation of CD163. Similar to recombinant CXCL4, releasate from human platelets also reduced CD163 expression. CXCL4-differentiated macrophages were unable to upregulate the atheroprotective enzyme heme oxygenase-1 at the RNA and protein level in response to hemoglobin–haptoglobin complexes. Immunofluorescence of human atherosclerotic plaques demonstrated presence of both CD68+CD163+ and CD68+CD163− macrophages. PF4 and CD163 gene expression within human atherosclerotic lesions were inversely correlated, supporting the in vivo relevance of CXCL4-induced downregulation of CD163. Conclusions CXCL4 may promote atherogenesis by suppressing CD163 in macrophages, which are then unable to upregulate the atheroprotective enzyme heme oxygenase-1 in response to hemoglobin. PMID:19910578

  5. Occupational skin cancer: Systematic review.

    PubMed

    Sena, Jéssica Suellen; Girão, Régio José Santiago; Carvalho, Sionara Melo Figueiredo de; Tavares, Rosielly Melo; Fonseca, Fernando Luiz Affonso; Silva, Patrícia Barros Aquino; Barbosa, Maria Clara Fortes Portela

    2016-01-01

    To analyze the epidemiological profile, risk factors in the workplace environment and prevention methods for professionals at risk of skin cancer. A systematic review of articles on occupational skin cancer, published in the Lilacs, Scielo, Medline and Cochrane Library from January 1st, 2008, to December 31st, 2013, was performed. The search included the following terms: "neoplasias cutâneas" (DeCS), "exposição ocupacional" (DeCS), "epidemiologia" (DeCS) as well as the keyword "prevenção", and their equivalents in English. After analyzing the titles and summaries of articles, the search strategy resulted in 83 references, of which 22 articles met the eligibility criteria. We found that sun exposure is the main occupational risk factor for skin cancer, causing outdoor workers to be the most vulnerable to developing occupational skin cancer. Professionals with low levels of education and European descent are at increased risk of developing this cancer. Outdoor workers are more vulnerable to developing occupational skin cancer, estimating that professionals with low level of education and European descent are at increased risk of developing this cancer. Therefore, companies need to invest more in the health of workers by providing protective equipment and thus preventing occupational skin cancer.

  6. Occupational contact allergic dermatitis in dentistry.

    PubMed

    Mikov, Ivan; Turkalj, Ivan; Jovanović, Marina

    2011-06-01

    Dental professionals may be at increased risk of developing occupational allergic diseases specially to methacrylates that can permeate protective disposable gloves. We presented a case of occupational allergic contact dermatitis in a 28-year-old dental technician. The patient had complained of itching and cracking of fingers for 6 months. The dermatitis improved over weekends. Skin erythema and scaling were present with primarily involvement of the fingertips. Patch testing with dental series gave positive vesicular reaction to methyl methacrylate. Follow-up after 6 months of allergen avoidance showed a complete regression of dermatitis. Methacrylates serve as bases for acrylic resins which are used in prosthetics. Methyl methacrylate as a small molecular acrylate can permeate thin protective disposable gloves. Using adequate personal protective equipment, like nitrile rubber gloves, is the most important preventive measure in this occupation. Health practitioners should recognize possible occupational hazards in dentistry and implement appropriate preventive measures to protect health of workers.

  7. Escherichia coli K1 induces pterin production for enhanced expression of Fcγ receptor I to invade RAW 264.7 macrophages

    PubMed Central

    Shanmuganathan, Muthusamy V.; Krishnan, Subramanian; Fu, Xiaowei; Prasadarao, Nemani V.

    2013-01-01

    Macrophages serve as permissive niches for Escherichia coli (E. coli) K1 to attain high grade bacteremia in the pathogenesis of meningitis in neonates. Although pterin levels are a diagnostic marker for immune activation, the role of macrophages in pterin production and in the establishment of meningitis is unknown. Here, we demonstrate that macrophages infected with E. coli K1 produce both neopterin and biopterin through increased expression of GTP-cyclohydrolase 1 (GCH1). Of note, increased production of biopterin enhances the expression of Fc-gamma receptor I (CD64), which in turn, aided the entry of E. coli K1 in macrophages while increased neopterin suppresses reactive oxygen species (ROS), thereby aiding bacterial survival. Inhibition of GCH1 by 2, 4-Diamino-6-hydroxypyrimidine (DAHP) prevented the E. coli K1 induced expression of CD64 in macrophages in vitro and the development of bacteremia in a newborn mouse model of meningitis. These studies suggest that targeting GCH1 could be therapeutic strategy for preventing neonatal meningitis by E. coli K1. PMID:24161960

  8. [News on occupational contact dermatitis].

    PubMed

    Crépy, Marie-Noëlle; Bensefa-Colas, Lynda

    2014-03-01

    Contact dermatitis--irritant contact dermatitis, allergic contact dermatitis and protein contact dermatitis--are the most common occupational skin diseases, most often localized to the hands. Contact urticaria is rarer The main occupational irritants are wet work, detergents and disinfectants, cutting oils, and solvents. The main occupational allergens are rubber additives, metals (chromium, nickel, cobalt), plastics (epoxy resins, acrylic), biocides and plants. Diagnosis is based on clinical examination, medical history and allergy testing. For a number of irritating or sensitizing agents, irritant or allergic dermatitis can be notified as occupational diseases. The two main prevention measures are reducing skin contact with irritants and complete avoidance of skin contact with offending allergens.

  9. The Macrophage Inhibitor CNI-1493 Blocks Metastasis in a Mouse Model of Ewing Sarcoma through Inhibition of Extravasation

    PubMed Central

    Hesketh, Anthony J.; Maloney, Caroline; Behr, Christopher A.; Edelman, Morris C.; Glick, Richard D.; Al-Abed, Yousef; Symons, Marc; Soffer, Samuel Z.; Steinberg, Bettie M.

    2015-01-01

    Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma. PMID:26709919

  10. The Macrophage Inhibitor CNI-1493 Blocks Metastasis in a Mouse Model of Ewing Sarcoma through Inhibition of Extravasation.

    PubMed

    Hesketh, Anthony J; Maloney, Caroline; Behr, Christopher A; Edelman, Morris C; Glick, Richard D; Al-Abed, Yousef; Symons, Marc; Soffer, Samuel Z; Steinberg, Bettie M

    2015-01-01

    Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma.

  11. Type I interferon induces necroptosis in macrophages during infection with Salmonella enterica serovar Typhimurium

    PubMed Central

    Robinson, Nirmal; McComb, Scott; Mulligan, Rebecca; Dudani, Renu; Krishnan, Lakshmi; Sad, Subash

    2014-01-01

    Salmonella enterica serovar Typhimurium (S. Typhimurium) is a virulent pathogen that induces rapid host death. Here we observed that host survival after infection with S. Typhimurium was enhanced in the absence of type I interferon signaling, with improved survival of mice deficient in the receptor for type I interferons (Ifnar1−/− mice) that was attributed to macrophages. Although there was no impairment in cytokine expression or inflammasome activation in Ifnar1−/− macrophages, they were highly resistant to S. Typhimurium–induced cell death. Specific inhibition of the kinase RIP1or knockdown of the gene encoding the kinase RIP3 prevented the death of wild-type macrophages, which indicated that necroptosis was a mechanism of cell death. Finally, RIP3-deficient macrophages, which cannot undergo necroptosis, had similarly less death and enhanced control of S. Typhimurium in vivo. Thus, we propose that S. Typhimurium induces the production of type I interferon, which drives necroptosis of macrophages and allows them to evade the immune response. PMID:22922364

  12. CSF-1–dependant donor-derived macrophages mediate chronic graft-versus-host disease

    PubMed Central

    Alexander, Kylie A.; Flynn, Ryan; Lineburg, Katie E.; Kuns, Rachel D.; Teal, Bianca E.; Olver, Stuart D.; Lor, Mary; Raffelt, Neil C.; Koyama, Motoko; Leveque, Lucie; Le Texier, Laetitia; Melino, Michelle; Markey, Kate A.; Varelias, Antiopi; Engwerda, Christian; Serody, Jonathan S.; Janela, Baptiste; Ginhoux, Florent; Clouston, Andrew D.; Blazar, Bruce R.; Hill, Geoffrey R.; MacDonald, Kelli P.A.

    2014-01-01

    Chronic GVHD (cGVHD) is the major cause of late, nonrelapse death following stem cell transplantation and characteristically develops in organs such as skin and lung. Here, we used multiple murine models of cGVHD to investigate the contribution of macrophage populations in the development of cGVHD. Using an established IL-17–dependent sclerodermatous cGVHD model, we confirmed that macrophages infiltrating the skin are derived from donor bone marrow (F4/80+CSF-1R+CD206+iNOS–). Cutaneous cGVHD developed in a CSF-1/CSF-1R–dependent manner, as treatment of recipients after transplantation with CSF-1 exacerbated macrophage infiltration and cutaneous pathology. Additionally, recipients of grafts from Csf1r–/– mice had substantially less macrophage infiltration and cutaneous pathology as compared with those receiving wild-type grafts. Neither CCL2/CCR2 nor GM-CSF/GM-CSFR signaling pathways were required for macrophage infiltration or development of cGVHD. In a different cGVHD model, in which bronchiolitis obliterans is a prominent manifestation, F4/80+ macrophage infiltration was similarly noted in the lungs of recipients after transplantation, and lung cGVHD was also IL-17 and CSF-1/CSF-1R dependent. Importantly, depletion of macrophages using an anti–CSF-1R mAb markedly reduced cutaneous and pulmonary cGVHD. Taken together, these data indicate that donor macrophages mediate the development of cGVHD and suggest that targeting CSF-1 signaling after transplantation may prevent and treat cGVHD. PMID:25157821

  13. [The implementation of legislation acts regarding prevention of occupational exposure to bloodborne pathogens from perspective of Poland as the ue country].

    PubMed

    Szczeniowski, Adam; Gańczak, Maria

    2011-01-01

    The paper presents the history of implementation of legislation related to prevention of occupational exposure to blood-borne pathogens in the U.S.A. and EU, including a detailed description of existing regulations. The pioneering role of American legislation in establishing relevant legal acts to prevent employees from sharp injuries is also stressed. In this context the European road towards safer work in the healthcare sector is discussed. The legal acts, currently functioning in the EU, including Council Directive 2010/32/EU of 10 May 2010, are described. The Directive implements the Framework Agreement on prevention from sharp injuries in the hospital and healthcare sector concluded by the European Hospital and Healthcare Employers' Association (HOSPEEM) and the European Federation of Public Service Unions (EPSU). The arguments for the universal implementation of legal acts, protecting medical staff in all EU Member States, are pointed out. As far as Poland is concerned, a great need for an urgent action mobilising all social partners (i.e., nurses, doctors, other employees at potential risk of acquiring an occupational infection, employers, professional organisations and scientific bodies) to develop relevant regulations and to assure sufficient funds for their broad implementation is underlined.

  14. Biology of Bony Fish Macrophages

    PubMed Central

    Hodgkinson, Jordan W.; Grayfer, Leon; Belosevic, Miodrag

    2015-01-01

    Macrophages are found across all vertebrate species, reside in virtually all animal tissues, and play critical roles in host protection and homeostasis. Various mechanisms determine and regulate the highly plastic functional phenotypes of macrophages, including antimicrobial host defenses (pro-inflammatory, M1-type), and resolution and repair functions (anti-inflammatory/regulatory, M2-type). The study of inflammatory macrophages in immune defense of teleosts has garnered much attention, and antimicrobial mechanisms of these cells have been extensively studied in various fish models. Intriguingly, both similarities and differences have been documented for the regulation of lower vertebrate macrophage antimicrobial defenses, as compared to what has been described in mammals. Advances in our understanding of the teleost macrophage M2 phenotypes likewise suggest functional conservation through similar and distinct regulatory strategies, compared to their mammalian counterparts. In this review, we discuss the current understanding of the molecular mechanisms governing teleost macrophage functional heterogeneity, including monopoetic development, classical macrophage inflammatory and antimicrobial responses as well as alternative macrophage polarization towards tissues repair and resolution of inflammation. PMID:26633534

  15. Biology of Bony Fish Macrophages.

    PubMed

    Hodgkinson, Jordan W; Grayfer, Leon; Belosevic, Miodrag

    2015-11-30

    Macrophages are found across all vertebrate species, reside in virtually all animal tissues, and play critical roles in host protection and homeostasis. Various mechanisms determine and regulate the highly plastic functional phenotypes of macrophages, including antimicrobial host defenses (pro-inflammatory, M1-type), and resolution and repair functions (anti-inflammatory/regulatory, M2-type). The study of inflammatory macrophages in immune defense of teleosts has garnered much attention, and antimicrobial mechanisms of these cells have been extensively studied in various fish models. Intriguingly, both similarities and differences have been documented for the regulation of lower vertebrate macrophage antimicrobial defenses, as compared to what has been described in mammals. Advances in our understanding of the teleost macrophage M2 phenotypes likewise suggest functional conservation through similar and distinct regulatory strategies, compared to their mammalian counterparts. In this review, we discuss the current understanding of the molecular mechanisms governing teleost macrophage functional heterogeneity, including monopoetic development, classical macrophage inflammatory and antimicrobial responses as well as alternative macrophage polarization towards tissues repair and resolution of inflammation.

  16. Fire Prevention Inspection Procedures.

    ERIC Educational Resources Information Center

    Pribyl, Paul F.

    Lesson plans are provided for a fire prevention inspection course of the Wisconsin Fire Service Training program. Objectives for the course are to enable students to describe and conduct fire prevention inspections, to identify and correct hazards common to most occupancies, to understand the types of building construction and occupancy, and to…

  17. Primary cilia disruption differentially affects the infiltrating and resident macrophage compartment in the liver.

    PubMed

    Zimmerman, Kurt A; Song, Cheng Jack; Gonzalez-Mize, Nancy; Li, Zhang; Yoder, Bradley K

    2018-06-01

    fibrocystic disease (HRFCD). We show that the number of infiltrating macrophages is significantly upregulated in HRFCD mouse models. Finally, we show that prevention of Ly6c hi infiltrating macrophage accumulation significantly reduces biliary fibrosis, but not biliary hyperplasia, suggesting that this population may be responsible for the fibrotic progression of the disease in HRFCD patients.

  18. Occupational poison ivy and oak dermatitis.

    PubMed

    Epstein, W L

    1994-07-01

    Among the growing and diverse groups of outdoor and environmental workers, poison ivy and poison oak continue to be the major cause of occupational contact dermatitis. This article reviews the practical and theoretic means to prevent poison ivy and poison oak dermatitis in workers occupationally exposed to these weeds.

  19. An Interview with an Occupational Therapist

    ERIC Educational Resources Information Center

    Crane, Sharon

    2005-01-01

    Sharon Crane is a pediatric occupational therapist with over 20 years of experience working with children and families. "Zero to Three" interviews her to discuss how occupational therapy may move beyond a strictly therapeutic orientation toward services that address wellness and prevention. Crane has created programs for parents and…

  20. Occupation and thyroid cancer.

    PubMed

    Aschebrook-Kilfoy, Briseis; Ward, Mary H; Della Valle, Curt T; Friesen, Melissa C

    2014-05-01

    Numerous occupational and environmental exposures have been shown to disrupt thyroid hormones, but much less is known about their relationships with thyroid cancer. Here we review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. The published literature was searched using the Web of Knowledge database for all articles through August 2013 that had in their text 'occupation' 'job' 'employment' or 'work' and 'thyroid cancer'. After excluding 10 mortality studies and 4 studies with less than 5 exposed incident cases, we summarised the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The studies were grouped by exposure/occupation category, study design and exposure assessment approach. Where available, gender-stratified results are reported. The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and healthcare occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations. Findings for other exposures and occupation groups were largely null. The majority of studies had few exposed cases and assessed exposure based on occupation or industry category, self-report, or generic (population-based) job exposure matrices. The suggestive, but inconsistent findings for many of the occupational exposures reviewed here indicate that more studies with larger numbers of cases and better exposure assessment are necessary, particularly for exposures known to disrupt thyroid homeostasis.

  1. [Quality assurance systems and occupational medicine system: an history twenty years along].

    PubMed

    Apostoli, Pietro

    2014-01-01

    Along the last tventy years, in our country the quality assurance systems and the occupational medicine deeply interacted both in theoretical and practical fields of interest at three levels: (i) the need of preventive and therefore of occupational medicine in quality assurance systems; (ii) the need on reverse of quality in prevention and occupational mnedicine mainly in qualification and updating process; (iii) the evidence, proofs of efficacy or appropriateness of different preventive procedures and occupational physician activities; (iv) the connection with European and national legal directives and with technical or good practice norms. Finally we discuss about the role of occupational physician as the global consultant for enterprise, as a mandatory strategic technical figure in a typical multidisciplinary processes as the implementation of the quality systems.

  2. Bioelectric modulation of macrophage polarization

    NASA Astrophysics Data System (ADS)

    Li, Chunmei; Levin, Michael; Kaplan, David L.

    2016-02-01

    Macrophages play a critical role in regulating wound healing and tissue regeneration by changing their polarization state in response to local microenvironmental stimuli. The native roles of polarized macrophages encompass biomaterials and tissue remodeling needs, yet harnessing or directing the polarization response has been largely absent as a potential strategy to exploit in regenerative medicine to date. Recent data have revealed that specific alteration of cells’ resting potential (Vmem) is a powerful tool to direct proliferation and differentiation in a number of complex tissues, such as limb regeneration, craniofacial patterning and tumorigenesis. In this study, we explored the bioelectric modulation of macrophage polarization by targeting ATP sensitive potassium channels (KATP). Glibenclamide (KATP blocker) and pinacidil (KATP opener) treatment not only affect macrophage polarization, but also influence the phenotype of prepolarized macrophages. Furthermore, modulation of cell membrane electrical properties can fine-tune macrophage plasticity. Glibenclamide decreased the secretion and gene expression of selected M1 markers, while pinacidil augmented M1 markers. More interestingly, glibencalmide promoted macrophage alternative activation by enhancing certain M2 markers during M2 polarization. These findings suggest that control of bioelectric properties of macrophages could offer a promising approach to regulate macrophage phenotype as a useful tool in regenerative medicine.

  3. Occupational injury among migrant workers in China: a systematic review.

    PubMed

    Fitzgerald, Simon; Chen, Xin; Qu, Hui; Sheff, Mira Grice

    2013-10-01

    This review considers the state of occupational injury surveillance and prevention among migrant workers in China and suggests areas of focus for future research on the topic. Bibliographic databases were searched for qualitative and quantitative studies on surveillance of and interventions to prevent occupational injury among migrant workers in mainland China. Additional abstracts were identified from the citations of relevant articles from the database search. Studies fitting the inclusion criteria were evaluated, and findings were extracted and summarised. The search uncovered 726 studies in the English-language databases searched, and 3109 in the Chinese database. This article analyses a total of 19 research articles that fit the inclusion criteria with qualitative or quantitative data on occupational injury surveillance and prevention of migrant workers in China. Despite evidence of the vulnerability of migrant workers in the workplace, there is little systematic surveillance of occupational injury and few evaluated interventions. Migrant workers account for a disproportionate burden of occupational injury morbidity and mortality in China. However, data are inconsistent and inadequate to detail injury incidence or to evaluate interventions. The following are suggestions to decrease injury incidence among migrants: strengthen the national system of occupational injury surveillance; focus surveillance and interventions on high-risk occupations employing migrants such as construction, manufacturing and small mining operations; improve occupational safety training and access to appropriate safety equipment; evaluate recent changes in occupational health and safety and evaluate outcome of multi-party interventions to reduce occupational injury among migrant workers.

  4. Macrophage Phenotype Controls Long-Term AKI Outcomes—Kidney Regeneration versus Atrophy

    PubMed Central

    Gröbmayr, Regina; Ryu, Mi; Lorenz, Georg; Hartter, Ingo; Mulay, Shrikant R.; Susanti, Heni Eka; Kobayashi, Koichi S.; Flavell, Richard A.; Anders, Hans-Joachim

    2014-01-01

    The mechanisms that determine full recovery versus subsequent progressive CKD after AKI are largely unknown. Because macrophages regulate inflammation as well as epithelial recovery, we investigated whether macrophage activation influences AKI outcomes. IL-1 receptor–associated kinase-M (IRAK-M) is a macrophage-specific inhibitor of Toll-like receptor (TLR) and IL-1 receptor signaling that prevents polarization toward a proinflammatory phenotype. In postischemic kidneys of wild-type mice, IRAK-M expression increased for 3 weeks after AKI and declined thereafter. However, genetic depletion of IRAK-M did not affect immunopathology and renal dysfunction during early postischemic AKI. Regarding long-term outcomes, wild-type kidneys regenerated completely within 5 weeks after AKI. In contrast, IRAK-M−/− kidneys progressively lost up to two-thirds of their original mass due to tubule loss, leaving atubular glomeruli and interstitial scarring. Moreover, M1 macrophages accumulated in the renal interstitial compartment, coincident with increased expression of proinflammatory cytokines and chemokines. Injection of bacterial CpG DNA induced the same effects in wild-type mice, and TNF-α blockade with etanercept partially prevented renal atrophy in IRAK-M−/− mice. These results suggest that IRAK-M induction during the healing phase of AKI supports the resolution of M1 macrophage– and TNF-α–dependent renal inflammation, allowing structural regeneration and functional recovery of the injured kidney. Conversely, IRAK-M loss-of-function mutations or transient exposure to bacterial DNA may drive persistent inflammatory mononuclear phagocyte infiltrates, which impair kidney regeneration and promote CKD. Overall, these results support a novel role for IRAK-M in the regulation of wound healing and tissue regeneration. PMID:24309188

  5. Effects of macrophage colony-stimulating factor on macrophages and their related cell populations in the osteopetrosis mouse defective in production of functional macrophage colony-stimulating factor protein.

    PubMed Central

    Umeda, S.; Takahashi, K.; Shultz, L. D.; Naito, M.; Takagi, K.

    1996-01-01

    The development of macrophage populations in osteopetrosis (op) mutant mice defective in production of functional macrophage colony-stimulating factor (M-CSF) and the response of these cell populations to exogenous M-CSF were used to classify macrophages into four groups: 1) monocytes, monocyte-derived macrophages, and osteoclasts, 2) MOMA-1-positive macrophages, 3) ER-TR9-positive macrophages, and 4) immature tissue macrophages. Monocytes, monocyte-derived macrophages, osteoclasts in bone, microglia in brain, synovial A cells, and MOMA-1- or ER-TR9-positive macrophages were deficient in op/op mice. The former three populations expanded to normal levels in op/op mice after daily M-CSF administration, indicating that they are developed and differentiated due to the effect of M-CSF supplied humorally. In contrast, the other cells did not respond or very slightly responded to M-CSF, and their development seems due to either M-CSF produced in situ or expression of receptor for M-CSF. Macrophages present in tissues of the mutant mice were immature and appear to be regulated by either granulocyte/macrophage colony-stimulating factor and/or interleukin-3 produced in situ or receptor expression. Northern blot analysis revealed different expressions of GM-CSF and IL-3 mRNA in various tissues of the op/op mice. However, granulocyte/macrophage colony-stimulating factor and interleukin-3 in serum were not detected by enzyme-linked immunosorbent assay. The immature macrophages differentiated and matured into resident macrophages after M-CSF administration, and some of these cells proliferated in response to M-CSF. Images Figure 4 Figure 6 Figure 8 Figure 10 Figure 11 PMID:8701995

  6. Resident alveolar macrophages are master regulators of arrested alveolarization in experimental bronchopulmonary dysplasia.

    PubMed

    Kalymbetova, Tatiana V; Selvakumar, Balachandar; Rodríguez-Castillo, José Alberto; Gunjak, Miša; Malainou, Christina; Heindl, Miriam Ruth; Moiseenko, Alena; Chao, Cho-Ming; Vadász, István; Mayer, Konstantin; Lohmeyer, Jürgen; Bellusci, Saverio; Böttcher-Friebertshäuser, Eva; Seeger, Werner; Herold, Susanne; Morty, Rory E

    2018-06-01

    Trophic functions for macrophages are emerging as key mediators of developmental processes, including bone, vessel, and mammary gland development. Yolk sac-derived macrophages mature in the distal lung shortly after birth. Myeloid-lineage macrophages are recruited to the lung and are activated under pathological conditions. These pathological conditions include bronchopulmonary dysplasia (BPD), a common complication of preterm birth characterized by stunted lung development, where the formation of alveoli is blocked. No study has addressed causal roles for immune cells in lung alveolarization. We employed antibody-based and transgenic death receptor-based depletion approaches to deplete or prevent lung recruitment of immune cell populations in a hyperoxia-based mouse model of BPD. Neither neutrophils nor exudate macrophages (which might include lung interstitial macrophages) contributed to structural perturbations to the lung that were provoked by hyperoxia; however, cells of the Csf1r-expressing monocyte/macrophage lineage were implicated as causal mediators of stunted lung development. We propose that resident alveolar macrophages differentiate into a population of CD45 + CD11c + SiglecF + CD11b + CD68 + MHCII + cells, which are activated by hyperoxia, and contribute to disturbances to the structural development of the immature lung. This is the first report that causally implicates immune cells in pathological disturbances to postnatal lung organogenesis. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  7. Stem bromelain-induced macrophage apoptosis and activation curtail Mycobacterium tuberculosis persistence.

    PubMed

    Mahajan, Sahil; Chandra, Vemika; Dave, Sandeep; Nanduri, Ravikanth; Gupta, Pawan

    2012-08-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis, has a remarkable ability to usurp its host's innate immune response, killing millions of infected people annually. One approach to manage infection is prevention through the use of natural agents. In this regard, stem bromelain (SBM), a pharmacologically active member of the sulfhydryl proteolytic enzyme family, obtained from Ananas comosus and possessing a remarkable ability to induce the innate and acquired immune systems, is important. We evaluated SBM's ability to induce apoptosis and free-radical generation in macrophages. We also studied antimycobacterial properties of SBM and its effect on foamy macrophages. SBM treatment of peritoneal macrophages resulted in the upregulation of proapoptotic proteins and downregulation of antiapoptotic proteins. Additionally, SBM treatment activated macrophages, curtailed the levels of free glutathione, and augmented the production of hydrogen peroxide, superoxide anion, peroxynitrite, and nitric oxide. SBM cleaves CD36 and reduced the formation of foam cells, the hallmark of M. tuberculosis infection. These conditions created an environment for the increased clearance of M. tuberculosis. Together these data provide a mechanism for antimycobacterial activity of SBM and provide important insights for the use of cysteine proteases as immunomodulatory agents.

  8. Vitamin A mediates conversion of monocyte-derived macrophages into tissue resident macrophages during alternative activation

    PubMed Central

    Gundra, Uma Mahesh; Girgis, Natasha M; Gonzalez, Michael A; Tang, Mei San; Van Der Zande, Hendrik J P; Lin, Jian-Da; Ouimet, Mireille; Ma, Lily J; Poles, Jordan A; Vozhilla, Nikollaq; Fisher, Edward A; Moore, Kathryn J; Loke, P’ng

    2017-01-01

    Whether activated inflammatory macrophages can adopt features of tissue resident macrophages and what mechanisms mediate this phenotypic conversion remain unclear. Here we show that vitamin A was required for phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80intCD206+PD-L2+MHCII+ macrophages into macrophages with a tissue-resident F4/80hiCD206−PD-L2−MHCII−UCP1+ phenotype in the peritoneal cavity of mice and during liver granuloma formation in mice infected with Schistosoma mansoni. Phenotypic conversion of F4/80intCD206+ macrophages into F4/80hiCD206− macrophages was associated with almost complete remodeling of the chromatin landscape, as well as alteration of the transcriptional profiles. Vitamin A deficient mice infected with S. mansoni had disrupted liver granuloma architecture and increased mortality, indicating that failure to convert from F4/80intCD206+ macrophages to F4/80hiCD206− macrophages may lead to dysregulated inflammation during helminth infection. PMID:28436955

  9. Interactions between neutrophils and macrophages promote macrophage killing of rat muscle cells in vitro

    NASA Technical Reports Server (NTRS)

    Nguyen, Hal X.; Tidball, James G.

    2003-01-01

    Current evidence indicates that the physiological functions of inflammatory cells are highly sensitive to their microenvironment, which is partially determined by the inflammatory cells and their potential targets. In the present investigation, interactions between neutrophils, macrophages and muscle cells that may influence muscle cell death are examined. Findings show that in the absence of macrophages, neutrophils kill muscle cells in vitro by superoxide-dependent mechanisms, and that low concentrations of nitric oxide (NO) protect against neutrophil-mediated killing. In the absence of neutrophils, macrophages kill muscle cells through a NO-dependent mechanism, and the presence of target muscle cells causes a three-fold increase in NO production by macrophages, with no change in the concentration of inducible nitric oxide synthase. Muscle cells that are co-cultured with both neutrophils and macrophages in proportions that are observed in injured muscle show cytotoxicity through a NO-dependent, superoxide-independent mechanism. Furthermore, the concentration of myeloid cells that is necessary for muscle killing is greatly reduced in assays that use mixed myeloid cell populations, rather than uniform populations of neutrophils or macrophages. These findings collectively show that the magnitude and mechanism of muscle cell killing by myeloid cells are modified by interactions between muscle cells and neutrophils, between muscle cells and macrophages and between macrophages and neutrophils.

  10. Potential role of macrophages as immunoregulators of pregnancy

    PubMed Central

    Mor, Gil; Abrahams, Vikki M

    2003-01-01

    The role of the maternal immune system during pregnancy has focused mainly on the aspect of immune tolerance to the invading trophoblast and, therefore, fetus. While this is a critical aspect of reproductive immunology, it is also important to consider the function of the maternal immune system in the promotion of implantation and maintenance of pregnancy. Apoptosis or cell death is not the final stage in tissue development. The quick and effective removal of apoptotic cells by tissue macrophages represents a vital process preventing "leak" of self-antigens and promoting the production of proliferative/survival factors. One of the key requirements of apoptotic cell clearance is the resolution of inflammatory conditions, which, as in the case of pregnancy, may have lethal consequences. This review will focus on decidual macrophages and their role on apoptosis and cell clearance during pregnancy. PMID:14651752

  11. MiR-146a modulates macrophage polarization by inhibiting Notch1 pathway in RAW264.7 macrophages.

    PubMed

    Huang, Cheng; Liu, Xue-Jiao; QunZhou; Xie, Juan; Ma, Tao-Tao; Meng, Xiao-Ming; Li, Jun

    2016-03-01

    Macrophages are heterogeneous and plastic cells which are able to undergo dynamic transition between M1 and M2 polarized phenotypes in response to the microenvironment signals. However, the underlying molecular mechanisms of macrophage polarization are still obscure. In the current study, it was revealed that miR-146a might play a pivotal role in macrophage polarization. As our results indicated, miR-146a was highly expressed in M2 macrophages rather than M1 macrophages. Over-expression of miR-146a resulted in significantly decreased production of pro-inflammatory cytokines including iNOS and TNF-α in M1 macrophages, while increased production of M2 marker genes such as Arg1 and CD206 in M2 macrophages. In contrast, knockdown of miR-146a promoted M1 macrophage polarization but diminished M2 macrophage polarization. Mechanistically, it was revealed that miR-146a modulated macrophage polarization by targeting Notch1. Of note, PPARγ was responsible as another target for miR-146a-mediated macrophage polarization. Taken together, it was suggested that miR-146a might serve as a molecular regulator in macrophage polarization and is a potential therapeutic target for inflammatory diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Macrophages: development and tissue specialization.

    PubMed

    Varol, Chen; Mildner, Alexander; Jung, Steffen

    2015-01-01

    Macrophages are myeloid immune cells that are strategically positioned throughout the body tissues, where they ingest and degrade dead cells, debris, and foreign material and orchestrate inflammatory processes. Here we review two major recent paradigm shifts in our understanding of tissue macrophage biology. The first is the realization that most tissue-resident macrophages are established prenatally and maintained through adulthood by longevity and self-renewal. Their generation and maintenance are thus independent from ongoing hematopoiesis, although the cells can be complemented by adult monocyte-derived macrophages. Second, aside from being immune sentinels, tissue macrophages form integral components of their host tissue. This entails their specialization in response to local environmental cues to contribute to the development and specific function of their tissue of residence. Factors that govern tissue macrophage specialization are emerging. Moreover, tissue specialization is reflected in discrete gene expression profiles of macrophages, as well as epigenetic signatures reporting actual and potential enhancer usage.

  13. Loss of autophagy enhances MIF/macrophage migration inhibitory factor release by macrophages.

    PubMed

    Lee, Jacinta P W; Foote, Andrew; Fan, Huapeng; Peral de Castro, Celia; Lang, Tali; Jones, Sarah A; Gavrilescu, Nichita; Mills, Kingston H G; Leech, Michelle; Morand, Eric F; Harris, James

    2016-06-02

    MIF (macrophage migration inhibitory factor [glycosylation-inhibiting factor]) is a pro-inflammatory cytokine expressed in multiple cells types, including macrophages. MIF plays a pathogenic role in a number of inflammatory diseases and has been linked to tumor progression in some cancers. Previous work has demonstrated that loss of autophagy in macrophages enhances secretion of IL1 family cytokines. Here, we demonstrate that loss of autophagy, by pharmacological inhibition or siRNA silencing of Atg5, enhances MIF secretion by monocytes and macrophages. We further demonstrate that this is dependent on mitochondrial reactive oxygen species (ROS). Induction of autophagy with MTOR inhibitors had no effect on MIF secretion, but amino acid starvation increased secretion. This was unaffected by Atg5 siRNA but was again dependent on mitochondrial ROS. Our data demonstrate that autophagic regulation of mitochondrial ROS plays a pivotal role in the regulation of inflammatory cytokine secretion in macrophages, with potential implications for the pathogenesis of inflammatory diseases and cancers.

  14. ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation

    PubMed Central

    Schumacher, Michael A; Hedl, Matija; Abraham, Clara; Bernard, Jessica K; Lozano, Patricia R; Hsieh, Jonathan J; Almohazey, Dana; Bucar, Edie B; Punit, Shivesh; Dempsey, Peter J; Frey, Mark R

    2017-01-01

    Efficient clearance of pro-inflammatory macrophages from tissues after resolution of a challenge is critical to prevent prolonged inflammation. Defects in clearance can contribute to conditions such as inflammatory bowel disease, and thus may be therapeutically targetable. However, the signaling pathways that induce termination of pro-inflammatory macrophages are incompletely defined. We tested whether the ErbB4 receptor tyrosine kinase, previously not known to have role in macrophage biology, is involved in this process. In vitro, pro-inflammatory activation of cultured murine and human macrophages induced ErbB4 expression; in contrast, other ErbB family members were not induced in pro-inflammatory cells, and other innate immune lineages (dendritic cells, neutrophils) did not express detectable ErbB4 levels. Treatment of activated pro-inflammatory macrophages with the ErbB4 ligand neuregulin-4 (NRG4) induced apoptosis. ErbB4 localized to the mitochondria in these cells. Apoptosis was accompanied by loss of mitochondrial membrane potential, and was dependent upon the proteases that generate the cleaved ErbB4 intracellular domain fragment, suggesting a requirement for this fragment and mitochondrial pathway apoptosis. In vivo, ErbB4 was highly expressed on pro-inflammatory macrophages but not neutrophils during experimental DSS colitis in C57Bl/6 mice. Active inflammation in this model suppressed NRG4 expression, which may allow for macrophage persistence and ongoing inflammation. Consistent with this notion, NRG4 levels rebounded during the recovery phase, and administration of exogenous NRG4 during colitis reduced colonic macrophage numbers and ameliorated inflammation. These data define a novel role for ErbB4 in macrophage apoptosis, and outline a mechanism of feedback inhibition that may promote resolution of colitis. PMID:28230865

  15. Occupational health issues affecting the pharmaceutical sales force.

    PubMed

    Harris, G; Mayho, G; Page, L

    2003-09-01

    The sales force forms a significant sub-population in the pharmaceutical industry workforce. Role and organizational characteristics, such as isolation, peripatetic working and car travel and the psychosocial and ergonomic hazards related to work tasks, present particular occupational health risks. To review the occupational risks associated with peripatetic sales force work and evidence for the effectiveness of preventive interventions. We carried out a review of the available literature between 1990 and 2003. The following hazards were identified as significant and worthy of further investigation for this occupational group: driving on company business; violence in the workplace; stress; ergonomic issues; and mobile phone use. To ensure effective prevention and management of employee health problems, specific health management strategies and interventions must be developed to meet the occupational health needs of this group.

  16. An overview of Japanese occupational health.

    PubMed Central

    Reich, M R; Frumkin, H

    1988-01-01

    This paper provides an overview of Japanese occupational health and evaluates the current situation from three perspectives. Major occupational health hazards are assessed using four sources of data, showing patterns similar to those found in other advanced industrial societies. Institutional structures for occupational health policy are then examined, illustrating strengths and weaknesses of the Japanese legal and administrative systems. Trade union activities are presented, indicating the constraints of enterprise unions, and the tendency for a greater orientation toward compensation than prevention. Significant occupational health problems persist among marginal workers in Japan, including women and various minority groups. The analysis demonstrates a record for occupational health in Japan considerably more mixed than the conventional view. PMID:2968056

  17. Imaging Macrophage-associated Inflammation.

    PubMed

    Foss, Catherine A; Sanchez-Bautista, Julian; Jain, Sanjay K

    2018-05-01

    Macrophages belong to the mononuclear phagocyte system comprising closely related cells of bone marrow origin. Activated macrophages are critical in several diseases such as tuberculosis, sarcoidosis, Crohn's disease, and atherosclerosis. Noninvasive imaging techniques that can specifically image activated macrophages could therefore help in differentiating various forms of inflammatory diseases and to monitor therapeutic responses. Copyright © 2017. Published by Elsevier Inc.

  18. Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation.

    PubMed

    Dang, Eric V; McDonald, Jeffrey G; Russell, David W; Cyster, Jason G

    2017-11-16

    Type I interferon restrains interleukin-1β (IL-1β)-driven inflammation in macrophages by upregulating cholesterol-25-hydroxylase (Ch25h) and repressing SREBP transcription factors. However, the molecular links between lipid metabolism and IL-1β production remain obscure. Here, we demonstrate that production of 25-hydroxycholesterol (25-HC) by macrophages is required to prevent inflammasome activation by the DNA sensor protein absent in melanoma 2 (AIM2). We find that in response to bacterial infection or lipopolysaccharide (LPS) stimulation, macrophages upregulate Ch25h to maintain repression of SREBP2 activation and cholesterol synthesis. Increasing macrophage cholesterol content is sufficient to trigger IL-1β release in a crystal-independent but AIM2-dependent manner. Ch25h deficiency results in cholesterol-dependent reduced mitochondrial respiratory capacity and release of mitochondrial DNA into the cytosol. AIM2 deficiency rescues the increased inflammasome activity observed in Ch25h -/- . Therefore, activated macrophages utilize 25-HC in an anti-inflammatory circuit that maintains mitochondrial integrity and prevents spurious AIM2 inflammasome activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Fluid-phase pinocytosis of LDL by macrophages: a novel target to reduce macrophage cholesterol accumulation in atherosclerotic lesions.

    PubMed

    Kruth, Howar S

    2013-01-01

    Circulating low-density lipoprotein (LDL) that enters the blood vessel wall is the main source of cholesterol that accumulates within atherosclerotic plaques. Much of the deposited cholesterol accumulates within plaque macrophages converting these macrophages into cholesterol-rich foamy looking cells. Cholesterol accumulation in macrophages contributes to cholesterol retention within the vessel wall, and promotes vessel wall inflammation and thrombogenicity. Thus, how macrophages accumulate cholesterol and become foam cells has been the subject of intense investigation. It is generally believed that macrophages accumulate cholesterol only through scavenger receptor-mediated uptake of modified LDL. However, an alternative mechanism for macrophage foam cell formation that does not depend on LDL modification or macrophage receptors has been elucidated. By this alternative mechanism, macrophages show receptor-independent uptake of unmodified native LDL that is mediated by fluid-phase pinocytosis. In receptor-independent, fluid-phase pinocytosis, macrophages take up LDL as part of the fluid that they ingest during micropinocytosis within small vesicles called micropinosomes, and by macropinocytosis within larger vacuoles called macropinosomes. This produces cholesterol accumulation in macrophages to levels characteristic of macrophage foam cells in atherosclerotic plaques. Fluid-phase pinocytosis of LDL is a plausible mechanism that can explain how macrophages accumulate cholesterol and become disease-causing foam cells. Fluid-phase pinocytosis of LDL is a relevant pathway to target for modulating macrophage cholesterol accumulation in atherosclerosis. Recent studies show that phosphoinositide 3-kinase (PI3K), liver X receptors (LXRs), the macrophage colony-stimulating factor (M-CSF) receptor, and protein kinase C (PKC) mediate macrophage macropinocytosis of LDL, and thus, these may be relevant targets to inhibit macrophage cholesterol accumulation in atherosclerosis.

  20. Moderate restriction of macrophage-tropic human immunodeficiency virus type 1 by SAMHD1 in monocyte-derived macrophages.

    PubMed

    Taya, Kahoru; Nakayama, Emi E; Shioda, Tatsuo

    2014-01-01

    Macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains are able to grow to high titers in human monocyte-derived macrophages. However, it was recently reported that cellular protein SAMHD1 restricts HIV-1 replication in human cells of the myeloid lineage, including monocyte-derived macrophages. Here we show that degradation of SAMHD1 in monocyte-derived macrophages was associated with moderately enhanced growth of the macrophage-tropic HIV-1 strain. SAMHD1 degradation was induced by treating target macrophages with vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 2 (HIV-2) particles containing viral protein X. For undifferentiated monocytes, HIV-2 particle treatment allowed undifferentiated monocytes to be fully permissive for productive infection by the macrophage-tropic HIV-1 strain. In contrast, untreated monocytes were totally resistant to HIV-1 replication. These results indicated that SAMHD1 moderately restricts even a macrophage-tropic HIV-1 strain in monocyte-derived macrophages, whereas the protein potently restricts HIV-1 replication in undifferentiated monocytes.

  1. Modulation of Decidual Macrophage Polarization by Macrophage Colony-Stimulating Factor Derived from First-Trimester Decidual Cells

    PubMed Central

    Li, Min; Piao, Longzhu; Chen, Chie-Pein; Wu, Xianqing; Yeh, Chang-Ching; Masch, Rachel; Chang, Chi-Chang; Huang, S. Joseph

    2017-01-01

    During human pregnancy, immune tolerance of the fetal semiallograft occurs in the presence of abundant maternal leukocytes. At the implantation site, macrophages comprise approximately 20% of the leukocyte population and act as primary mediators of tissue remodeling. Decidual macrophages display a balance between anti-inflammatory and proinflammatory phenotypes. However, a shift to an M1 subtype is reported in preeclampsia. Granulocyte-macrophage colony-stimulating-factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are major differentiating factors that mediate M1 and M2 polarization, respectively. Previously, we observed the following: i) the preeclamptic decidua contains an excess of both macrophages and GM-CSF, ii) the preeclampsia-associated proinflammatory cytokines, IL-1β and tumor necrosis factor-α, markedly enhance GM-CSF and M-CSF expression in cultured leukocyte-free first-trimester decidual cells (FTDCs), iii) FTDC-secreted GM-CSF polarizes macrophages toward an M1 subtype. The microenvironment is a key determinant of macrophage phenotype. Thus, we examined proinflammatory stimulation of FTDC-secreted M-CSF and its role in macrophage development. Immunofluorescence staining demonstrated elevated M-CSF–positive decidual cell numbers in preeclamptic decidua. In FTDCs, IL-1β and tumor necrosis factor-α signal through the NF-κB pathway to induce M-CSF production, which does the following: i) enhances differentiation of and elevates CD163 expression in macrophages, ii) increases macrophage phagocytic capacity, and iii) inhibits signal-regulatory protein α expression by macrophages. These findings suggest that FTDC-secreted M-CSF modulates the decidual immune balance by inducing M2 macrophage polarization and phagocytic capacity in response to proinflammatory stimuli. PMID:26970370

  2. M1 Macrophages but Not M2 Macrophages Are Characterized by Upregulation of CRP Expression via Activation of NFκB: a Possible Role for Ox-LDL in Macrophage Polarization.

    PubMed

    Kaplan, Marielle; Shur, Anna; Tendler, Yvgeny

    2018-04-23

    Arterial macrophages comprise a heterogeneous population: pro-inflammatory (M1) and anti-inflammatory (M2). Since C-reactive protein (CRP) is produced by macrophages in atherosclerotic lesions, understanding of CRP regulation in macrophages could be crucial to decipher inflammatory patterns in atherogenesis. We aimed to analyze CRP expression in M1/M2 macrophages and to question whether it involves NFκB signaling pathway. Furthermore, we questioned whether oxidative stress affect macrophage phenotype and modulate macrophage CRP expression. M1/M2 macrophage polarization was validated using THP-1 macrophages. CRP mRNA and protein expression were determined using real-time PCR and immunohistochemistry. Involvement of NFκB was determined by nuclear translocation of p50 subunit and the use of NFκB inhibitor. Involvement of oxidative stress in macrophage phenotypes induction was studied using oxidized-LDL (Ox-LDL) and antioxidants. M1 macrophages were characterized by elevated CRP mRNA expression (by 67%), CRP protein levels (by 108%), and upregulation of NFκB activation compared to control, but these features were not shared by M2 macrophages. Macrophages incubation with Ox-LDL led to a moderate M1 phenotype combined with a M2 phenotype, correlated with increased CRP mRNA expression. Antioxidants inhibited by up to 86% IL6 expression but did not significantly affect IL10 secretion. Antioxidants significantly inhibited CRP expression in M1 macrophages, but not in M2 macrophages. Elevated expression of CRP was characteristic of M1 macrophages rather than M2 through NFκB activation. Oxidative stress could be one of the endogenous triggers for macrophage activation to a mixed M1 and M2 phenotype, in association with increased expression of CRP.

  3. Occupational injury among migrant workers in China: a systematic review

    PubMed Central

    Fitzgerald, Simon; Chen, Xin; Qu, Hui; Sheff, Mira Grice

    2017-01-01

    Objectives This review considers the state of occupational injury surveillance and prevention among migrant workers in China and suggests areas of focus for future research on the topic. Methods Bibliographic databases were searched for qualitative and quantitative studies on surveillance of and interventions to prevent occupational injury among migrant workers in mainland China. Additional abstracts were identified from the citations of relevant articles from the database search. Studies fitting the inclusion criteria were evaluated, and findings were extracted and summarised. Results The search uncovered 726 studies in the English-language databases searched, and 3109 in the Chinese database. This article analyses a total of 19 research articles that fit the inclusion criteria with qualitative or quantitative data on occupational injury surveillance and prevention of migrant workers in China. Despite evidence of the vulnerability of migrant workers in the workplace, there is little systematic surveillance of occupational injury and few evaluated interventions. Conclusions Migrant workers account for a disproportionate burden of occupational injury morbidity and mortality in China. However, data are inconsistent and inadequate to detail injury incidence or to evaluate interventions. The following are suggestions to decrease injury incidence among migrants: strengthen the national system of occupational injury surveillance; focus surveillance and interventions on high-risk occupations employing migrants such as construction, manufacturing and small mining operations; improve occupational safety training and access to appropriate safety equipment; evaluate recent changes in occupational health and safety and evaluate outcome of multi-party interventions to reduce occupational injury among migrant workers. PMID:23710065

  4. [A cost-benefit analysis of occupational disease reporting in China].

    PubMed

    Tang, X Z; Zeng, Q; Liu, D S

    2017-03-20

    Objective: To perform a cost-benefit analysis of the occupational disease reporting system in China, and to provide a basis for effective resource allocation. Methods: The data on the cost of occupational diseases were collected from China Health Statistics Yearbook 2013, the estimated benefit data were collected from published articles in China and foreign countries, and the probability data were collected from the occupational diseasereports published by health and family planning administrative departments. Adecision-making tree was used for the cost-benefit analysis. Results: The estimated cost of occupational disease reporting was about 102.47 million yuan/year, consisting of a cost of reporting in national medical institutions of 1.25 million yuan/year, a management cost of 30.35 million yuan/year, a management cost in local public health institutions of 69.80 million yuan/year, a management cost in national public health institutions of 370 thousand yuan/year, and a cost of construction and maintenance of reporting system of 700 thousand yuan/year. The results of the decision tree analysis showed that when an occupational disease monitoring system was established, the incremental input for occupational disease monitoring and prevention/control was 2.1 billion yuan/year, the output was 6.5 billion yuan/year, and the benefit of occupational disease reporting system was 4.4 billion yuan/year. Conclusion: The benefit of occupational disease reporting system depends on the cost-benefit of occupational disease prevention and control measures, and proper prevention and control measures are extremely important for improving the benefit of occupational disease reporting system.

  5. Suicide Rates by Occupational Group - 17 States, 2012.

    PubMed

    McIntosh, Wendy LiKamWa; Spies, Erica; Stone, Deborah M; Lokey, Colby N; Trudeau, Aimée-Rika T; Bartholow, Brad

    2016-07-01

    In 2012, approximately 40,000 suicides were reported in the United States, making suicide the 10th leading reported cause of death for persons aged ≥16 years (1). From 2000 to 2012, rates of suicide among persons in this age group increased 21.1%, from 13.3 per 100,000 to 16.1 (1). To inform suicide prevention efforts, CDC analyzed suicide by occupational group, by ascribing occupational codes to 12,312 suicides in 17 states in 2012 from the National Violent Death Reporting System (NVDRS) (2). The frequency of suicide in different occupational groups was examined, and rates of suicide were calculated by sex and age group for these categories. Persons working in the farming, fishing, and forestry group had the highest rate of suicide overall (84.5 per 100,000 population) and among males (90.5); the highest rates of suicide among females occurred among those working in protective service occupations (14.1). Overall, the lowest rate of suicide (7.5) was found in the education, training, and library occupational group. Suicide prevention approaches directed toward persons aged ≥16 years that enhance social support, community connectedness, access to preventive services, and the reduction of stigma and barriers to help-seeking are needed.

  6. Health Occupations: Grade 8. Cluster II.

    ERIC Educational Resources Information Center

    Calhoun, Olivia H.

    A curriculum guide for grade 8, the document is devoted to the occupational cluster "Health Occupations." It is divided into four units: the hospital, preventive medicine, drug use and abuse, and alcohol and tobacco. Each unit is introduced by a statement of the topic, the unit's purpose, main ideas, quests, and a list of career…

  7. IFN-ε protects primary macrophages against HIV infection.

    PubMed

    Tasker, Carley; Subbian, Selvakumar; Gao, Pan; Couret, Jennifer; Levine, Carly; Ghanny, Saleena; Soteropoulos, Patricia; Zhao, Xilin; Landau, Nathaniel; Lu, Wuyuan; Chang, Theresa L

    2016-12-08

    IFN-ε is a unique type I IFN that is not induced by pattern recognition response elements. IFN-ε is constitutively expressed in mucosal tissues, including the female genital mucosa. Although the direct antiviral activity of IFN-ε was thought to be weak compared with IFN-α, IFN-ε controls Chlamydia muridarum and herpes simplex virus 2 in mice, possibly through modulation of immune response. We show here that IFN-ε induces an antiviral state in human macrophages that blocks HIV-1 replication. IFN-ε had little or no protective effect in activated CD4 + T cells or transformed cell lines unless activated CD4 + T cells were infected with replication-competent HIV-1 at a low MOI. The block to HIV infection of macrophages was maximal after 24 hours of treatment and was reversible. IFN-ε acted on early stages of the HIV life cycle, including viral entry, reverse transcription, and nuclear import. The protection did not appear to operate through known type I IFN-induced HIV host restriction factors, such as APOBEC3A and SAMHD1. IFN-ε-stimulated immune mediators and pathways had the signature of type I IFNs but were distinct from IFN-α in macrophages. IFN-ε induced significant phagocytosis and ROS, which contributed to the block to HIV replication. These findings indicate that IFN-ε induces an antiviral state in macrophages that is mediated by different factors than those induced by IFN-α. Understanding the mechanism of IFN-ε-mediated HIV inhibition through immune modulation has implications for prevention.

  8. IFN-ε protects primary macrophages against HIV infection

    PubMed Central

    Tasker, Carley; Subbian, Selvakumar; Gao, Pan; Couret, Jennifer; Levine, Carly; Ghanny, Saleena; Soteropoulos, Patricia; Zhao, Xilin; Landau, Nathaniel; Lu, Wuyuan

    2016-01-01

    IFN-ε is a unique type I IFN that is not induced by pattern recognition response elements. IFN-ε is constitutively expressed in mucosal tissues, including the female genital mucosa. Although the direct antiviral activity of IFN-ε was thought to be weak compared with IFN-α, IFN-ε controls Chlamydia muridarum and herpes simplex virus 2 in mice, possibly through modulation of immune response. We show here that IFN-ε induces an antiviral state in human macrophages that blocks HIV-1 replication. IFN-ε had little or no protective effect in activated CD4+ T cells or transformed cell lines unless activated CD4+ T cells were infected with replication-competent HIV-1 at a low MOI. The block to HIV infection of macrophages was maximal after 24 hours of treatment and was reversible. IFN-ε acted on early stages of the HIV life cycle, including viral entry, reverse transcription, and nuclear import. The protection did not appear to operate through known type I IFN-induced HIV host restriction factors, such as APOBEC3A and SAMHD1. IFN-ε–stimulated immune mediators and pathways had the signature of type I IFNs but were distinct from IFN-α in macrophages. IFN-ε induced significant phagocytosis and ROS, which contributed to the block to HIV replication. These findings indicate that IFN-ε induces an antiviral state in macrophages that is mediated by different factors than those induced by IFN-α. Understanding the mechanism of IFN-ε–mediated HIV inhibition through immune modulation has implications for prevention. PMID:27942584

  9. Relationship of occupational and non-occupational stress with smoking in automotive industry workers.

    PubMed

    Hassani, Somayeh; Yazdanparast, Taraneh; Seyedmehdi, Seyed Mohammad; Ghaffari, Mostafa; Attarchi, Mirsaeed; Bahadori, Baharak

    2014-01-01

    Tobacco use is the second cause of death and first cause of preventable mortality worldwide. Smoking in the workplace is particularly concerning. Smoking-free workplaces decrease the risk of exposure of non-smoking personnel to cigarette smoke. Recent studies have mostly focused on the effect of daily or non-occupational stressors (in comparison with occupational stress) on prevalence of smoking. Occupational stress is often evaluated in workplaces for smoking cessation or control programs, but the role of non-occupational stressors is often disregarded in this respect. This cross-sectional study was conducted in an automobile manufacturing company. The response of automotive industry workers to parts of the validated, reliable, Farsi version of Musculoskeletal Intervention Center (MUSIC)-Norrtalje questionnaire was evaluated. A total of 3,536 factory workers participated in this study. Data were analyzed using SPSS and P<0.05 was considered statistically significant. The correlation of smoking with demographic factors, occupational stressors and life events was evaluated. The results of logistic regression analysis showed that even after adjusting for the confounding factors, cigarette smoking was significantly correlated with age, sex, level of education, job control and life events (P<0.05). The results showed that of occupational and non-occupational stressors, only job control was correlated with cigarette smoking. Non-occupational stressors had greater effect on cigarette smoking. Consideration of both non-occupational and occupational stressors can enhance the success of smoking control programs. On the other hand, a combination of smoking control and stress (occupational and non-occupational) control programs can be more effective than smoking cessation interventions alone.

  10. Soluble human leukocyte antigen G5 polarizes differentiation of macrophages toward a decidual macrophage-like phenotype.

    PubMed

    Lee, Cheuk-Lun; Guo, YiFan; So, Kam-Hei; Vijayan, Madhavi; Guo, Yue; Wong, Vera H H; Yao, YuanQing; Lee, Kai-Fai; Chiu, Philip C N; Yeung, William S B

    2015-10-01

    What are the actions of soluble human leukocyte antigen G5 (sHLAG5) on macrophage differentiation? sHLAG5 polarizes the differentiation of macrophages toward a decidual macrophage-like phenotype, which could regulate fetomaternal tolerance and placental development. sHLAG5 is a full-length soluble isoform of human leukocyte antigen implicated in immune tolerance during pregnancy. Low or undetectable circulating level of sHLAG5 in first trimester of pregnancy is associated with pregnancy complications such as pre-eclampsia and spontaneous abortion. Decidual macrophages are located in close proximity to invasive trophoblasts, and are involved in regulating fetomaternal tolerance and placental development. Human peripheral blood monocytes were differentiated into macrophages by treatment with granulocyte macrophage colony-stimulating factor in the presence or absence of recombinant sHLAG5 during the differentiation process. The phenotypes and the biological activities of the resulting macrophages were compared. Recombinant sHLAG5 was produced in Escherichia coli BL21 and the protein identity was verified by tandem mass spectrometry. The expression of macrophage markers were analyzed by flow cytometry and quantitative PCR. Phagocytosis was determined by flow cytometry. Indoleamine 2,3-dioxygenase 1 expression and activity were measured by western blot analysis and kynurenine assay, respectively. Cell proliferation and cell cycling were determined by fluorometric cell proliferation assay and flow cytometry, respectively. Cytokine secretion was determined by cytokine array and ELISA kits. Intracellular cytokine expression was measured by flow cytometry. Cell invasion and migration were determined by trans-well invasion and migration assay, respectively. sHLAG5 drove the differentiation of macrophages with 'immuno-modulatory' characteristics, including reduced expression of M1 macrophage marker CD86 and increased expression of M2 macrophage marker CD163. sHLAG5-polarized

  11. Vascular endothelial growth factor modified macrophages transdifferentiate into endothelial-like cells and decrease foam cell formation.

    PubMed

    Yan, Dan; He, Yujuan; Dai, Jun; Yang, Lili; Wang, Xiaoyan; Ruan, Qiurong

    2017-06-30

    Macrophages are largely involved in the whole process of atherosclerosis from an initiation lesion to an advanced lesion. Endothelial disruption is the initial step and macrophage-derived foam cells are the hallmark of atherosclerosis. Promotion of vascular integrity and inhibition of foam cell formation are two important strategies for preventing atherosclerosis. How can we inhibit even the reverse negative role of macrophages in atherosclerosis? The present study was performed to investigate if overexpressing endogenous human vascular endothelial growth factor (VEGF) could facilitate transdifferentiation of macrophages into endothelial-like cells (ELCs) and inhibit foam cell formation. We demonstrated that VEGF-modified macrophages which stably overexpressed human VEGF (hVEGF 165 ) displayed a high capability to alter their phenotype and function into ELCs in vitro Exogenous VEGF could not replace endogenous VEGF to induce the transdifferentiation of macrophages into ELCs in vitro We further showed that VEGF-modified macrophages significantly decreased cytoplasmic lipid accumulation after treatment with oxidized LDL (ox-LDL). Moreover, down-regulation of CD36 expression in these cells was probably one of the mechanisms of reduction in foam cell formation. Our results provided the in vitro proof of VEGF-modified macrophages as atheroprotective therapeutic cells by both promotion of vascular repair and inhibition of foam cell formation. © 2017 The Author(s).

  12. Maternal occupational exposure to polycyclic aromatic hydrocarbons and craniosynostosis among offspring in the National Birth Defects Prevention Study.

    PubMed

    O'Brien, Jacqueline L; Langlois, Peter H; Lawson, Christina C; Scheuerle, Angela; Rocheleau, Carissa M; Waters, Martha A; Symanski, Elaine; Romitti, Paul A; Agopian, A J; Lupo, Philip J

    2016-01-01

    Evidence in animal models and humans suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) may lead to birth defects. To our knowledge, this relationship has not been evaluated for craniosynostosis, a birth defect characterized by the premature closure of sutures in the skull. We conducted a case-control study to examine associations between maternal occupational exposure to PAHs and craniosynostosis. We used data from craniosynostosis cases and control infants in the National Birth Defects Prevention Study (NBDPS) with estimated delivery dates from 1997 to 2002. Industrial hygienists reviewed occupational data from the computer-assisted telephone interview and assigned a yes/no rating of probable occupational PAH exposure for each job from 1 month before conception through delivery. We used logistic regression to assess the association between occupational exposure to PAHs and craniosynostosis. The prevalence of exposure was 5.3% in case mothers (16/300) and 3.7% in control mothers (107/2,886). We observed a positive association between exposure to PAHs during the 1 month before conception through the third month of pregnancy and craniosynostosis (odds ratio [OR] = 1.75; 95% confidence interval [CI], 1.01-3.05) after adjusting for maternal age and maternal education. The number of cases for each craniosynostosis subtype limited subtype analyses to sagittal craniosynostosis; the odds ratio remained similar (OR = 1.76, 95% CI, 0.82-3.75), but was not significant. Our findings support a moderate association between maternal occupational exposure to PAHs and craniosynostosis. Additional work is needed to better characterize susceptibility and the role PAHs may play on specific craniosynostosis subtypes. © 2015 Wiley Periodicals, Inc.

  13. [Current status of occupational health and related countermeasures in Guangzhou, China].

    PubMed

    Zeng, W F; Wu, S H; Wang, Z; Liu, Y M

    2016-02-20

    To investigate the current status of occupational health and related countermeasures in Guangzhou, China. Related data were collected from occupational poisoning accident investigation, diagnosis and identification of occupational diseases, and the occupational disease hazard reporting system, and the statistical data of occupational health in Guangzhou were analyzed retrospectively. The number of enterprises reporting for occupational disease hazards in Guangzhou was 20 890, and the total number of workers was 1 457 583. The number of workers exposed to occupational hazards was 284 233, and the cumulative number of workers with occupational diseases was 1 502. There were many risk factors for occupational diseases in enterprises, and there were a large number of workers with occupational diseases, as well as newly diagnosed cases. From 2001 to 2014, the total number of cases of occupational diseases was 958. The situation for the prevention and control of occupational diseases is grim in Guangzhou. Occupational health supervision and law enforcement should be enhanced, the three-level supervision system should be established and perfected, and the occupational health supervision system with a combination of "prevention, treatment, and protection" should be established and promoted, so as to gradually establish a technical service support system for occupational health.

  14. Escherichia coli K1 induces pterin production for enhanced expression of Fcγ receptor I to invade RAW 264.7 macrophages.

    PubMed

    Shanmuganathan, Muthusamy V; Krishnan, Subramanian; Fu, Xiaowei; Prasadarao, Nemani V

    2014-02-01

    Macrophages serve as permissive niches for Escherichia coli (E. coli) K1 to attain high grade bacteremia in the pathogenesis of meningitis in neonates. Although pterin levels are a diagnostic marker for immune activation, the role of macrophages in pterin production and in the establishment of meningitis is unknown. Here, we demonstrate that macrophages infected with E. coli K1 produce both neopterin and biopterin through increased expression of GTP-cyclohydrolase 1 (GCH1). Of note, increased production of biopterin enhances the expression of Fc-gamma receptor I (CD64), which in turn, aided the entry of E. coli K1 in macrophages while increased neopterin suppresses reactive oxygen species (ROS), thereby aiding bacterial survival. Inhibition of GCH1 by 2, 4-Diamino-6-hydroxypyrimidine (DAHP) prevented the E. coli K1 induced expression of CD64 in macrophages in vitro and the development of bacteremia in a newborn mouse model of meningitis. These studies suggest that targeting GCH1 could be therapeutic strategy for preventing neonatal meningitis by E. coli K1. Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  15. Occupational accidents aboard merchant ships

    PubMed Central

    Hansen, H; Nielsen, D; Frydenberg, M

    2002-01-01

    Objectives: To investigate the frequency, circumstances, and causes of occupational accidents aboard merchant ships in international trade, and to identify risk factors for the occurrence of occupational accidents as well as dangerous working situations where possible preventive measures may be initiated. Methods: The study is a historical follow up on occupational accidents among crew aboard Danish merchant ships in the period 1993–7. Data were extracted from the Danish Maritime Authority and insurance data. Exact data on time at risk were available. Results: A total of 1993 accidents were identified during a total of 31 140 years at sea. Among these, 209 accidents resulted in permanent disability of 5% or more, and 27 were fatal. The mean risk of having an occupational accident was 6.4/100 years at sea and the risk of an accident causing a permanent disability of 5% or more was 0.67/100 years aboard. Relative risks for notified accidents and accidents causing permanent disability of 5% or more were calculated in a multivariate analysis including ship type, occupation, age, time on board, change of ship since last employment period, and nationality. Foreigners had a considerably lower recorded rate of accidents than Danish citizens. Age was a major risk factor for accidents causing permanent disability. Change of ship and the first period aboard a particular ship were identified as risk factors. Walking from one place to another aboard the ship caused serious accidents. The most serious accidents happened on deck. Conclusions: It was possible to clearly identify work situations and specific risk factors for accidents aboard merchant ships. Most accidents happened while performing daily routine duties. Preventive measures should focus on workplace instructions for all important functions aboard and also on the prevention of accidents caused by walking around aboard the ship. PMID:11850550

  16. Human Induced Pluripotent Stem Cell-Derived Macrophages for Unraveling Human Macrophage Biology.

    PubMed

    Zhang, Hanrui; Reilly, Muredach P

    2017-11-01

    Despite a substantial appreciation for the critical role of macrophages in cardiometabolic diseases, understanding of human macrophage biology has been hampered by the lack of reliable and scalable models for cellular and genetic studies. Human induced pluripotent stem cell (iPSC)-derived macrophages (IPSDM), as an unlimited source of subject genotype-specific cells, will undoubtedly play an important role in advancing our understanding of the role of macrophages in human diseases. In this review, we summarize current literature in the differentiation and characterization of IPSDM at phenotypic, functional, and transcriptomic levels. We emphasize the progress in differentiating iPSC to tissue resident macrophages, and in understanding the ontogeny of in vitro differentiated IPSDM that resembles primitive hematopoiesis, rather than adult definitive hematopoiesis. We review the application of IPSDM in modeling both Mendelian genetic disorders and host-pathogen interactions. Finally, we highlighted the potential areas of research using IPSDM in functional validation of coronary artery disease loci in genome-wide association studies, functional genomic analyses, drug testing, and cell therapeutics in cardiovascular diseases. © 2017 American Heart Association, Inc.

  17. Tripeptidyl peptidase II promotes maturation of caspase-1 in Shigella flexneri-induced macrophage apoptosis.

    PubMed

    Hilbi, H; Puro, R J; Zychlinsky, A

    2000-10-01

    The invasive enteropathogenic bacterium Shigella flexneri activates apoptosis in macrophages. Shigella-induced apoptosis requires caspase-1. We demonstrate here that tripeptidyl peptidase II (TPPII), a cytoplasmic, high-molecular-weight protease, participates in the apoptotic pathway triggered by Shigella. The TPPII inhibitor Ala-Ala-Phe-chloromethylketone (AAF-cmk) and clasto-lactacystin beta-lactone (lactacystin), an inhibitor of both TPPII and the proteasome, protected macrophages from Shigella-induced apoptosis. AAF-cmk was more potent than lactacystin and irreversibly blocked Shigella-induced apoptosis by 95% at a concentration of 1 microM. Conversely, peptide aldehyde and peptide vinylsulfone proteasome inhibitors had little effect on Shigella-mediated cytotoxicity. Both AAF-cmk and lactacystin prevented the maturation of pro-caspase-1 and its substrate pro-interleukin 1beta in Shigella-infected macrophages, indicating that TPPII is upstream of caspase-1. Neither of these compounds directly inhibited caspase-1. AAF-cmk and lactacystin did not impair macrophage phagocytosis or the ability of Shigella to escape the macrophage phagosome. TPPII was also found to be involved in apoptosis induced by ATP and the protein kinase inhibitor staurosporine. We propose that TPPII participates in apoptotic pathways.

  18. Tripeptidyl Peptidase II Promotes Maturation of Caspase-1 in Shigella flexneri-Induced Macrophage Apoptosis

    PubMed Central

    Hilbi, Hubert; Puro, Robyn J.; Zychlinsky, Arturo

    2000-01-01

    The invasive enteropathogenic bacterium Shigella flexneri activates apoptosis in macrophages. Shigella-induced apoptosis requires caspase-1. We demonstrate here that tripeptidyl peptidase II (TPPII), a cytoplasmic, high-molecular-weight protease, participates in the apoptotic pathway triggered by Shigella. The TPPII inhibitor Ala-Ala-Phe-chloromethylketone (AAF-cmk) and clasto-lactacystin β-lactone (lactacystin), an inhibitor of both TPPII and the proteasome, protected macrophages from Shigella-induced apoptosis. AAF-cmk was more potent than lactacystin and irreversibly blocked Shigella-induced apoptosis by 95% at a concentration of 1 μM. Conversely, peptide aldehyde and peptide vinylsulfone proteasome inhibitors had little effect on Shigella-mediated cytotoxicity. Both AAF-cmk and lactacystin prevented the maturation of pro-caspase-1 and its substrate pro-interleukin 1β in Shigella-infected macrophages, indicating that TPPII is upstream of caspase-1. Neither of these compounds directly inhibited caspase-1. AAF-cmk and lactacystin did not impair macrophage phagocytosis or the ability of Shigella to escape the macrophage phagosome. TPPII was also found to be involved in apoptosis induced by ATP and the protein kinase inhibitor staurosporine. We propose that TPPII participates in apoptotic pathways. PMID:10992446

  19. Macrophages: Their Emerging Roles in Bone

    PubMed Central

    Sinder, Benjamin P; Pettit, Allison R; McCauley, Laurie K

    2016-01-01

    Macrophages are present in nearly all tissues and are critical for development, homeostasis, and regeneration. Resident tissue macrophages of bone, termed osteal macrophages, are recently classified myeloid cells that are distinct from osteoclasts. Osteal macrophages are located immediately adjacent to osteoblasts, regulate bone formation, and play diverse roles in skeletal homeostasis. Genetic or pharmacological modulation of macrophages in vivo results in significant bone phenotypes, and these phenotypes depend on which macrophage subsets are altered. Macrophages are also key mediators of osseous wound healing and fracture repair, with distinct roles at various stages of the repair process. A central function of macrophages is their phagocytic ability. Each day, billions of cells die in the body and efferocytosis (phagocytosis of apoptotic cells) is a critical process in both clearing dead cells and recruitment of replacement progenitor cells to maintain homeostasis. Recent data suggest a role for efferocytosis in bone biology and these new mechanisms are outlined. Finally, although macrophages have an established role in primary tumors, emerging evidence suggests that macrophages in bone support cancers which preferentially metastasize to the skeleton. Collectively, this developing area of osteoimmunology raises new questions and promises to provide novel insights into pathophysiologic conditions as well as therapeutic and regenerative approaches vital for skeletal health. PMID:26531055

  20. microRNA-150 inhibits the formation of macrophage foam cells through targeting adiponectin receptor 2

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Jing; Zhang, Suhua, E-mail: drsuhuangzhang@qq.com

    Transformation of macrophages into foam cells plays a critical role in the pathogenesis of atherosclerosis. The aim of this study was to determine the expression and biological roles of microRNA (miR)-150 in the formation of macrophage foam cells and to identify its functional target(s). Exposure to 50 μg/ml oxidized low-density lipoprotein (oxLDL) led to a significant upregulation of miR-150 in THP-1 macrophages. Overexpression of miR-150 inhibited oxLDL-induced lipid accumulation in THP-1 macrophages, while knockdown of miR-150 enhanced lipid accumulation. apoA-I- and HDL-mediated cholesterol efflux was increased by 66% and 43%, respectively, in miR-150-overexpressing macrophages relative to control cells. In contrast, downregulationmore » of miR-150 significantly reduced cholesterol efflux from oxLDL-laden macrophages. Bioinformatic analysis and luciferase reporter assay revealed adiponectin receptor 2 (AdipoR2) as a direct target of miR-150. Small interfering RNA-mediated downregulation of AdipoR2 phenocopied the effects of miR-150 overexpression, reducing lipid accumulation and facilitating cholesterol efflux in oxLDL-treated THP-1 macrophages. Knockdown of AdipoR2 induced the expression of proliferator-activated receptor gamma (PPARγ), liver X receptor alpha (LXRα), ABCA1, and ABCG1. Moreover, pharmacological inhibition of PPARγ or LXRα impaired AdipoR2 silencing-induced upregulation of ABCA1 and ABCG1. Taken together, our results indicate that miR-150 can attenuate oxLDL-induced lipid accumulation in macrophages via promotion of cholesterol efflux. The suppressive effects of miR-150 on macrophage foam cell formation are mediated through targeting of AdipoR2. Delivery of miR-150 may represent a potential approach to prevent macrophage foam cell formation in atherosclerosis. -- Highlights: •miR-150 inhibits macrophage foam cell formation. •miR-150 accelerates cholesterol efflux from oxLDL-laden macrophages. •miR-150 suppresses macrophage foam

  1. New developments in occupational dermatology.

    PubMed

    Diepgen, Thomas L

    2016-09-01

    Occupational skin diseases according to BK No. 5101 - "severe or recurrent skin diseases which have forced the person to discontinue all occupational activities that caused or could cause the development, worsening, or recurrence of the disease" - is the most commonly reported notifiable occupational diseases in Germany. Following the optimization of measures of primary, secondary, and tertiary prevention, today most individuals affected are able to continue their profession. With the revision of the German ordinance on occupational diseases (BKV) in January 2015, skin cancer caused by UV irradiation was added to the list of occupational diseases. The new occupational disease (BK) 5103 is defined as "squamous cell carcinoma or multiple actinic keratoses of the skin caused by natural UV irradiation". In this context, "multiple" signifies the occurrence of either more than five individual actinic keratosis lesions over the course of 12 months or the presence of field cancerization of > 4 cm(2) . In the following review, important aspects of this new occupational disease will be highlighted and discussed. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  2. Occupation and Thyroid Cancer

    PubMed Central

    Aschebrook-Kilfoy, Briseis; Ward, Mary H.; Valle, Curt T. Della; Friesen, Melissa C.

    2014-01-01

    Objectives Numerous occupational and environmental exposures have been shown to disrupt thyroid hormones, but much less is known about their relationships with thyroid cancer. Here we review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. Methods The published literature was searched using the Web of Knowledge database for all articles through August 2013 that had in their text “occupation” “job” ”employment” or “work” and “thyroid cancer”. After excluding 10 mortality studies and 4 studies with less than 5 exposed incident cases, we summarized the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The studies were grouped by exposure/occupation category, study design, and exposure assessment approach. Where available, gender stratified results are reported. Results The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and health care occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations. Findings for other exposures and occupation groups were largely null. The majority of studies had few exposed cases and assessed exposure based on occupation or industry category, self-report, or generic (population-based) job exposure matrices. Conclusion The suggestive, but inconsistent findings for many of the occupational exposures reviewed here indicate that more studies with larger numbers of cases and better exposure assessment are necessary, particularly for exposures known to disrupt thyroid homeostasis. PMID:24604144

  3. Proliferating macrophages prevail in atherosclerosis.

    PubMed

    Randolph, Gwendalyn J

    2013-09-01

    Macrophages accumulate in atherosclerotic lesions during the inflammation that is part of atherosclerosis development and progression. A new study in mice indicates that the accumulation of macrophages in atherosclerotic plaques depends on local macrophage proliferation rather than the recruitment of circulating monocytes.

  4. Lysozyme activates Enterococcus faecium to induce necrotic cell death in macrophages.

    PubMed

    Gröbner, Sabine; Fritz, Evelyn; Schoch, Friederike; Schaller, Martin; Berger, Alexander C; Bitzer, Michael; Autenrieth, Ingo B

    2010-10-01

    Enterococci are commensal organisms in the alimentary tract. However, they can cause a variety of life-threatening infections, especially in nosocomial settings. We hypothesized that induction of cell death might enable these facultative pathogenic bacteria to evade the innate immune response and to cause infections of their host. We demonstrate that E. faecium when exposed to lysozyme induces cell death in macrophages in vitro and in vivo. Flow cytometric analyses of J774A.1 macrophages infected with E. faecium revealed loss of cell membrane integrity indicated by uptake of propidium iodide and decrease of the inner mitochondrial transmembrane potential DeltaPsi(m). Inhibition of caspases, treatment of macrophages with cytochalasin D, or rifampicin did not prevent cells from dying, suggesting cell death mechanisms that are independent of caspase activation, bacterial uptake, and intracellular bacterial replication. Characteristics of necrotic cell death were demonstrated by both lack of procaspase 3 activation and cell shrinkage, electron microscopy, and release of lactate dehydrogenase. Pretreatment of E. faecium with lysozyme and subsequently with broad spectrum protease considerably reduced cell death, suggesting that a bacterial surface protein is causative for cell death induction. Moreover, in a mouse peritonitis model we demonstrated that E. faecium induces cell death of peritoneal macrophages in vivo. Altogether, our results show that enterococci, under specific conditions such as exposure to lysozyme, induce necrotic cell death in macrophages, which might contribute to disseminated infections by these facultative pathogenic bacteria.

  5. Origin and Functions of Tissue Macrophages

    PubMed Central

    Epelman, Slava; Lavine, Kory J.; Randolph, Gwendalyn J.

    2015-01-01

    Macrophages are distributed in tissues throughout the body and contribute to both homeostasis and disease. Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes. Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are functionally interchangeable or have unique roles at steady state. This new understanding also prompts reconsideration of the function of circulating monocytes. Classical Ly6chi monocytes patrol the extravascular space in resting organs, and Ly6clo nonclassical monocytes patrol the vasculature. Inflammation triggers monocytes to differentiate into macrophages, but whether resident and newly recruited macrophages possess similar functions during inflammation is unclear. Here, we define the tools used for identifying the complex origin of tissue macrophages and discuss the relative contributions of tissue niche versus ontological origin to the regulation of macrophage functions during steady state and inflammation. PMID:25035951

  6. Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Song, Jun; Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX; Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX

    2010-02-26

    Objective: The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Strategies to reduce lipid accumulation in macrophages may have therapeutic potential for preventing and treating atherosclerosis and cardiovascular complications. The antidiabetic drug metformin has been reported to reduce lipid accumulation in adipocytes. In this study, we examined the effects of metformin on lipid accumulation in macrophages and investigated the mechanisms involved. Methods and results: We observed that metformin significantly reduced palmitic acid (PA)-induced intracellular lipid accumulation in macrophages. Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4)more » which was involved in PA-induced lipid accumulation. Quantitative real-time PCR showed that metformin regulates FABP4 expression at the transcriptional level. We identified forkhead transcription factor FOXO1 as a positive regulator of FABP4 expression. Inhibiting FOXO1 expression with FOXO1 siRNA significantly reduced basal and PA-induced FABP4 expression. Overexpression of wild-type FOXO1 and constitutively active FOXO1 significantly increased FABP4 expression, whereas dominant negative FOXO1 dramatically decreased FABP4 expression. Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity. Conclusions: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription. Thus, metformin may have a protective effect against lipid accumulation in macrophages and may serve as a therapeutic agent for preventing and treating atherosclerosis in metabolic syndrome.« less

  7. Immune Evasion Strategies of Pathogens in Macrophages: the Potential for Limiting Pathogen Transmission.

    PubMed

    Ren, Yuwei; Khan, Faheem Ahmed; Pandupuspitasari, Nuruliarizki Shinta; Zhang, Shujun

    2017-01-01

    Preventing pathogen transmission to a new host is of major interest to the immunologist and could benefit from a detailed investigation of pathogen immune evasion strategies. The first line of defense against pathogen invasion is provided by macrophages. When they sense pathogens, macrophages initiate signals to inflammatory and pro-inflammatory cytokines through pattern recognition receptors (PRRs) subsequently mediating phagocytosis and inflammation. The macrophage immune machinery classically includes two subsets: the activated M1 and the activated M2 that respond accordingly in diverse immune challenges. The lipid and glycogen metabolic pathways work together with the lysosome to help the mature phagosome to degrade and eliminate intracellular pathogens in macrophages. The viral evasion strategies are even more complex due to the interplay between autophagy and apoptosis. However, pathogens evolve several strategies to camouflage themselves against immune responses in order to ensure their survival, replication and transmission. These strategies include the muting of PRRs initiated inflammatory responses, attenuation of M1 and/or induction of M2 macrophages, suppression of autophago-lysosomal formation, interference with lipid and glycogen metabolism, and viral mediation of autophagy and apoptosis cross-talk to enhance viral replication. This review focuses on pathogen immune evasion methods and on the strategies used by the host against camouflaged pathogens.

  8. Candida albicans Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions.

    PubMed

    Wagener, Jeanette; MacCallum, Donna M; Brown, Gordon D; Gow, Neil A R

    2017-01-24

    The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid l-arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host's arginase activity to prevent the conversion of l-arginine to nitric oxide. We report here that C. albicans blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the C. albicans-induced arginase activity with the arginase-specific substrate inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that C. albicans influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore, C. albicans modulates l-arginine metabolism in macrophages during an infection, potentiating its own survival. The availability and metabolism of amino acids are increasingly recognized as crucial regulators of immune functions. In acute infections, the conversion

  9. Occupational skin diseases in cleaning and kitchen employees: course and quality of life after measures of secondary individual prevention.

    PubMed

    Soder, Stefanie; Diepgen, Thomas L; Radulescu, Magdalena; Apfelbacher, Christian J; Bruckner, Thomas; Weisshaar, Elke

    2007-08-01

    Cleaning and kitchen employees have an increased risk of suffering from occupational dermatoses. Prevention including improving individual skin care and skin protection behavior, health education, optimizing diagnostics and therapy as well as avoidance of occupational skin disease (BK 5101) is important. Participants in the courses were patients suspected of having an occupational skin disease. Besides socio-demographic and disease-related data, health-related quality of life (QL) was measured using the SF-36 and Skindex-29. One year later all participants were interviewed by telephone about the course of their skin disease. Out of 212 participants, 84.0 % were female. The mean age was 41.6 (SD = 10.8) years.168 patients (79.2 %) suffered from hand dermatitis,with irritant contact dermatitis being the predominant diagnosis (46.2 %,n = 98). One year later 65.4 % (n = 85) of the patients interviewed still suffered from hand dermatitis.9.2 % (n = 12) had meanwhile quit their job due to the skin disease. QL was impaired in all age groups being lower with increasing age of the patients. The follow-up confirmed the positive impact of the skin protection courses on patients' skin disease and well-being. Occupational skin diseases impair health-related quality of life in these professions but disease severity does not seem to play a key role.

  10. Hypericin-mediated sonodynamic therapy induces autophagy and decreases lipids in THP-1 macrophage by promoting ROS-dependent nuclear translocation of TFEB.

    PubMed

    Li, Xuesong; Zhang, Xin; Zheng, Longbin; Kou, Jiayuan; Zhong, Zhaoyu; Jiang, Yueqing; Wang, Wei; Dong, Zengxiang; Liu, Zhongni; Han, Xiaobo; Li, Jing; Tian, Ye; Zhao, Yajun; Yang, Liming

    2016-12-22

    Lipid catabolism disorder is the primary cause of atherosclerosis. Transcription factor EB (TFEB) prevents atherosclerosis by activating macrophage autophagy to promote lipid degradation. Hypericin-mediated sonodynamic therapy (HY-SDT) has been proved non-invasively inducing THP-1-derived macrophage apoptosis; however, it is unknown whether macrophage autophagy could be triggered by HY-SDT to influence cellular lipid catabolism via regulating TFEB. Here, we report that HY-SDT resulted in the time-dependent THP-1-derived macrophage autophagy activation through AMPK/AKT/mTOR pathway. Besides, TFEB nuclear translocation in macrophage was triggered by HY-SDT to promote autophagy activation and lysosome regeneration which enhanced lipid degradation in response to atherogenic lipid stressors. Moreover, following HY-SDT, the ABCA1 expression level was increased to promote lipid efflux in macrophage, and the expression levels of CD36 and SR-A were decreased to inhibit lipid uptake, both of which were prevented by TFEB knockdown. These results indicated that TFEB nuclear translocation activated by HY-SDT was not only the key regulator of autophagy activation and lysosome regeneration in macrophage to promote lipolysis, but also had a crucial role in reverse cholesterol transporters to decrease lipid uptake and increase lipid efflux. Reactive oxygen species (ROS) were adequately generated in macrophage by HY-SDT. Further, ROS scavenger N-acetyl-l-cysteine abolished HY-SDT-induced TFEB nuclear translocation and autophagy activation, implying that ROS were the primary upstream factors responsible for these effects during HY-SDT. In summary, our data indicate that HY-SDT decreases lipid content in macrophage by promoting ROS-dependent nuclear translocation of TFEB to influence consequent autophagy activation and cholesterol transporters. Thus, HY-SDT may be beneficial for atherosclerosis via TFEB regulation to ameliorate lipid overload in atherosclerotic plaques.

  11. Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury.

    PubMed

    Masola, Valentina; Zaza, Gianluigi; Bellin, Gloria; Dall'Olmo, Luigi; Granata, Simona; Vischini, Gisella; Secchi, Maria Francesca; Lupo, Antonio; Gambaro, Giovanni; Onisto, Maurizio

    2018-02-01

    Heparanase (HPSE) is part of the biologic network triggered by ischemia/reperfusion (I/R) injury, a complication of renal transplantation and acute kidney injury. During this period, the kidney or graft undergoes a process of macrophages recruitment and activation. HPSE may therefore control these biologic effects. We measured the ability of HPSE and its inhibitor, SST0001, to regulate macrophage polarization and the crosstalk between macrophages and HK-2 renal tubular cells during in vitro hypoxia/reoxygenation (H/R). Furthermore, we evaluated in vivo renal inflammation, macrophage polarization, and histologic changes in mice subjected to monolateral I/R and treated with SST0001 for 2 or 7 d. The in vitro experiments showed that HPSE sustained M1 macrophage polarization and modulated apoptosis, the release of damage associated molecular patterns in post-H/R tubular cells, the synthesis of proinflammatory cytokines, and the up-regulation of TLRs on both epithelial cells and macrophages. HPSE also regulated M1 polarization induced by H/R-injured tubular cells and the partial epithelial-mesenchymal transition of these epithelial cells by M1 macrophages. All these effects were prevented by inhibiting HPSE. Furthermore, the inhibition of HPSE in vivo reduced inflammation and M1 polarization in mice undergoing I/R injury, partially restored renal function and normal histology, and reduced apoptosis. These results show for the first time that HPSE regulates macrophage polarization as well as renal damage and repair after I/R. HPSE inhibitors could therefore provide a new pharmacologic approach to minimize acute kidney injury and to prevent the chronic profibrotic damages induced by I/R.-Masola, V., Zaza, G., Bellin, G., Dall'Olmo, L., Granata, S., Vischini, G., Secchi, M. F., Lupo, A., Gambaro, G., Onisto, M. Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury.

  12. Effect of low extracellular pH on NF-κB activation in macrophages.

    PubMed

    Gerry, A B; Leake, D S

    2014-04-01

    Many diseases, including atherosclerosis, involve chronic inflammation. The master transcription factor for inflammation is NF-κB. Inflammatory sites have a low extracellular pH. Our objective was to demonstrate the effect of pH on NF-κB activation and cytokine secretion. Mouse J774 macrophages or human THP-1 or monocyte-derived macrophages were incubated at pH 7.0-7.4 and inflammatory cytokine secretion and NF-κB activity were measured. A pH of 7.0 greatly decreased pro-inflammatory cytokine secretion (TNF or IL-6) by J774 macrophages, but not THP-1 or human monocyte-derived macrophages. Upon stimulation of mouse macrophages, the levels of IκBα, which inhibits NF-κB, fell but low pH prevented its later increase, which normally restores the baseline activity of NF-κB, even though the levels of mRNA for IκBα were increased. pH 7.0 greatly increased and prolonged NF-κB binding to its consensus promoter sequence, especially the anti-inflammatory p50:p50 homodimers. Human p50 was overexpressed using adenovirus in THP-1 macrophages and monocyte-derived macrophages to see if it would confer pH sensitivity to NF-κB activity in human cells. Overexpression of p50 increased p50:p50 DNA-binding and in THP-1 macrophages inhibited considerably TNF and IL-6 secretion, but there was still no effect of pH on p50:p50 DNA binding or cytokine secretion. A modest decrease in pH can sometimes have marked effects on NF-κB activation and cytokine secretion and might be one reason to explain why mice normally develop less atherosclerosis than do humans. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  13. NFAT5-Regulated Macrophage Polarization Supports the Proinflammatory Function of Macrophages and T Lymphocytes.

    PubMed

    Tellechea, Mónica; Buxadé, Maria; Tejedor, Sonia; Aramburu, Jose; López-Rodríguez, Cristina

    2018-01-01

    Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings. We found that both in classically and alternatively polarized macrophages, NFAT5 enhanced functions associated with a proinflammatory profile such as bactericidal capacity and the ability to promote Th1 polarization over Th2 responses. In this regard, NFAT5 upregulated the Th1-stimulatory cytokine IL-12 in classically activated macrophages, whereas in alternatively polarized ones it enhanced the expression of the pro-Th1 mediators Fizz-1 and arginase 1, indicating that it could promote proinflammatory readiness by regulating independent genes in differently polarized macrophages. Finally, adoptive transfer assays in vivo revealed a reduced antitumor capacity in NFAT5-deficient macrophages against syngeneic Lewis lung carcinoma and ID8 ovarian carcinoma cells, a defect that in the ID8 model was associated with a reduced accumulation of effector CD8 T cells at the tumor site. Altogether, detailed analysis of the effect of NFAT5 in pro- and anti-inflammatory macrophages uncovered its ability to regulate distinct genes under both polarization modes and revealed its predominant role in promoting proinflammatory macrophage functions. Copyright © 2017 by The American Association of Immunologists, Inc.

  14. Relationship of Occupational and Non-Occupational Stress with Smoking in Automotive Industry Workers

    PubMed Central

    Hassani, Somayeh; Yazdanparast, Taraneh; Ghaffari, Mostafa; Attarchi, Mirsaeed; Bahadori, Baharak

    2014-01-01

    Background Tobacco use is the second cause of death and first cause of preventable mortality worldwide. Smoking in the workplace is particularly concerning. Smoking-free workplaces decrease the risk of exposure of non-smoking personnel to cigarette smoke. Recent studies have mostly focused on the effect of daily or non-occupational stressors (in comparison with occupational stress) on prevalence of smoking. Occupational stress is often evaluated in workplaces for smoking cessation or control programs, but the role of non-occupational stressors is often disregarded in this respect. Materials and Methods This cross-sectional study was conducted in an automobile manufacturing company. The response of automotive industry workers to parts of the validated, reliable, Farsi version of Musculoskeletal Intervention Center (MUSIC)-Norrtalje questionnaire was evaluated. A total of 3,536 factory workers participated in this study. Data were analyzed using SPSS and P<0.05 was considered statistically significant. Results The correlation of smoking with demographic factors, occupational stressors and life events was evaluated. The results of logistic regression analysis showed that even after adjusting for the confounding factors, cigarette smoking was significantly correlated with age, sex, level of education, job control and life events (P<0.05). Conclusion The results showed that of occupational and non-occupational stressors, only job control was correlated with cigarette smoking. Non-occupational stressors had greater effect on cigarette smoking. Consideration of both non-occupational and occupational stressors can enhance the success of smoking control programs. On the other hand, a combination of smoking control and stress (occupational and non-occupational) control programs can be more effective than smoking cessation interventions alone. PMID:25506374

  15. Granulocyte-macrophage and macrophage colony-stimulating factors differentially regulate alpha v integrin expression on cultured human macrophages.

    PubMed

    De Nichilo, M O; Burns, G F

    1993-03-15

    The colony-stimulating factors (CSFs) greatly influence mature macrophage function in vitro: macrophage (M)-CSF induces maturation of monocytes and enhances differentiated cell function; granulocyte-macrophage (GM)-CSF stimulates a variety of antimicrobial functions. In vivo M-CSF is thought to promote differentiation, and GM-CSF is thought to potentiate the inflammatory response. One mechanism by which these differential effects may be achieved is through the receptor-mediated interaction of macrophages with their extracellular matrix. Here we show that M-CSF induces specifically the expression of the alpha v beta 5 integrin receptor, whereas GM-CSF rapidly induces mRNA and surface expression of the alpha v beta 3 integrin. The M-CSF-treated cells acquire a flattened epitheloid phenotype, and on vitronectin the alpha v beta 5 is located in adhesion plaques. These cells do not bind collagen or laminin. In contrast, cells treated with GM-CSF adopt an elongated phenotype on a number of substrates, including collagen and laminin, and express alpha v beta 3 at the leading edge of cells on vitronectin. These results suggest that a primary means by which the CSFs exert their individual effects on mature cells may be through regulating integrin expression.

  16. Behavior-Based Safety and Occupational Risk Management

    ERIC Educational Resources Information Center

    Geller, E. Scott

    2005-01-01

    The behavior-based approach to managing occupational risk and preventing workplace injuries is reviewed. Unlike the typical top-down control approach to industrial safety, behavior-based safety (BBS) provides tools and procedures workers can use to take personal control of occupational risks. Strategies the author and his colleagues have been…

  17. Evidence for the separate human T-lymphocyte subpopulations that collaborate with autologous monocyte/macrophages in the elaboration of colony-stimulating activity and those that suppress this collaboration.

    PubMed

    Verma, D S; Johnston, D A; McCredie, K B

    1983-11-01

    We investigated the interaction of monocyte/macrophages and autologous T lymphocytes in the methanol extraction residue (MER) of BCG-induced production of granulocyte-macrophage colony-stimulating activity (CSA). Coincubation of monocyte/macrophages and T lymphocytes at a 1:3 ratio produces an optimum collaboration; a change to a 1:9 ratio diminished this collaboration. Coincubation of monocyte/macrophages and T lymphocytes primed with lithium carbonate (2 meq/liter) for 40 hr synergistically increased CSA elaboration and prevented the decline in CSA noted for the 1:9 monocyte/macrophage: T lymphocyte ratio. In contrast, concanavalin-A-primed T lymphocytes did not enhance CSA elaboration at any monocyte/macrophage:T lymphocyte ratio except, occasionally, at 1:9. However, this was overcome if the T lymphocytes were primed with both concanavalin-A and lithium carbonate before their coincubation with monocyte/macrophages. Further cell-mixing experiments revealed that concanavalin-A-primed T lymphocytes contained a subpopulation that suppressed monocyte/macrophage and T-lymphocyte collaboration. Activation of suppressor T lymphocytes could be effectively prevented by lithium carbonate and, in a dose-dependent manner, by irradiation. Also, suppressor T lymphocytes not only diminished the elaboration of colony-stimulating factor(s), but also elaborated an inhibitor of granulocyte-macrophage colony-forming cells. We further demonstrated that the respective hemopoietic helper and suppressor T-lymphocyte activities could be enriched with OKT8- (or OKT4+) and OKT8+ subpopulations.

  18. Adipocyte fetuin-A contributes to macrophage migration into adipose tissue and polarization of macrophages.

    PubMed

    Chatterjee, Priyajit; Seal, Soma; Mukherjee, Sandip; Kundu, Rakesh; Mukherjee, Sutapa; Ray, Sukanta; Mukhopadhyay, Satinath; Majumdar, Subeer S; Bhattacharya, Samir

    2013-09-27

    Macrophage infiltration into adipose tissue during obesity and their phenotypic conversion from anti-inflammatory M2 to proinflammatory M1 subtype significantly contributes to develop a link between inflammation and insulin resistance; signaling molecule(s) for these events, however, remains poorly understood. We demonstrate here that excess lipid in the adipose tissue environment may trigger one such signal. Adipose tissue from obese diabetic db/db mice, high fat diet-fed mice, and obese diabetic patients showed significantly elevated fetuin-A (FetA) levels in respect to their controls; partially hepatectomized high fat diet mice did not show noticeable alteration, indicating adipose tissue to be the source of this alteration. In adipocytes, fatty acid induces FetA gene and protein expressions, resulting in its copious release. We found that FetA could act as a chemoattractant for macrophages. To simulate lipid-induced inflammatory conditions when proinflammatory adipose tissue and macrophages create a niche of an altered microenvironment, we set up a transculture system of macrophages and adipocytes; the addition of fatty acid to adipocytes released FetA into the medium, which polarized M2 macrophages to M1. This was further confirmed by direct FetA addition to macrophages. Taken together, lipid-induced FetA from adipocytes is an efficient chemokine for macrophage migration and polarization. These findings open a new dimension for understanding obesity-induced inflammation.

  19. Macrophages and cellular immunity in Drosophila melanogaster

    PubMed Central

    Gold, Katrina S.; Brückner, Katja

    2016-01-01

    The invertebrate Drosophila melanogaster has been a powerful model for understanding blood cell development and immunity. Drosophila is a holometabolous insect, which transitions through a series of life stages from embryo, larva and pupa to adulthood. In spite of this, remarkable parallels exist between Drosophila and vertebrate macrophages, both in terms of development and function. More than 90% of Drosophila blood cells (hemocytes) are macrophages (plasmatocytes), making this highly tractable genetic system attractive for studying a variety of questions in macrophage biology. In vertebrates, recent findings revealed that macrophages have two independent origins: self-renewing macrophages, which reside and proliferate in local microenvironments in a variety of tissues, and macrophages of the monocyte lineage, which derive from hematopoietic stem or progenitor cells. Like vertebrates, Drosophila possesses two macrophage lineages with a conserved dual ontogeny. These parallels allow us to take advantage of the Drosophila model when investigating macrophage lineage specification, maintenance and amplification, and the induction of macrophages and their progenitors by local microenvironments and systemic cues. Beyond macrophage development, Drosophila further serves as a paradigm for understanding the mechanisms underlying macrophage function and cellular immunity in infection, tissue homeostasis and cancer, throughout development and adult life. PMID:27117654

  20. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity.

    PubMed

    Xiong, Xiao-Qing; Geng, Zhi; Zhou, Bing; Zhang, Feng; Han, Ying; Zhou, Ye-Bo; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2018-06-01

    Obesity-induced chronic inflammation is critical in the pathogenesis of insulin resistance, and the recruitment and proinflammatory activation of adipose tissue macrophages (ATMs) is important for the development of this process. Here, we examined the effects of fibronectin type III domain-containing 5 (FNDC5) on inflammation and insulin resistance in high-fat diet-induced obese mice. Male wild-type (WT) and FNDC5 -/- mice were fed with standard chow (Ctrl) or high fat diet (HFD) for 20 weeks to induce obesity and insulin resistance. Firstly, effects of FNDC5 gene deletion on obesity, insulin resistance, macrophage accumulation and polarization and adipose tissue inflammation were determined in mice. Secondly, the macrophage polarity shift was further examined with flow cytometry in isolated stromal vascular fraction (SVF). Thirdly, the effects of exogenous FNDC5 on lipopolysaccharide (LPS)-induced macrophage polarization, inflammation and the underlying signaling mechanism were investigated in RAW264.7 macrophages and primary mouse peritoneal cavity macrophages (PMs). Finally, the therapeutic effects of FNDC5 overexpression were examined in HFD-induced obese WT and FNDC5 -/- mice. FNDC5 gene deletion aggravated obesity, insulin resistance, fat accumulation and inflammation accompanied with enhanced AMPK inhibition, macrophages recruitment and M1 polarization in mice fed with HFD. Exogenous FNDC5 inhibited LPS-induced M1 macrophage polarization and inflammatory cytokine production via AMPK phosphorylation in both RAW264.7 macrophages and PMs. FNDC5 overexpression attenuated insulin resistance, AMPK inhibition, M1 macrophage polarization and inflammatory cytokine production in adipose tissue of obese WT and FNDC5 -/- mice. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in HFD-induced obesity. FNDC5 plays several beneficial roles in obesity and may be used as a therapeutic regimen for preventing

  1. Occupational Hazards Education for Nursing Staff through Web-Based Learning

    PubMed Central

    Tung, Chen-Yin; Chang, Chia-Chen; Ming, Jin-Lain; Chao, Keh-Ping

    2014-01-01

    This study aims to explore the efficiency of using online education as an intervention measure to prevent occupational hazards in a clinical nursing setting. The subjects were 320 female nursing staff from two hospitals in Taiwan. The questionnaire results indicated that the subjects primarily experienced human factor occupational hazards, as well as psychological and social hazards. Specifically, 73.1% and 69.8% of the subjects suffered from poor sleep quality and low back pain, respectively. After web-based learning, the experimental group had higher post-test scores than the control group in terms of knowledge, attitudes, and practices (KAP). However, there was only a significant difference (p < 0.05) in their knowledge about the prevention of occupational hazards. It is suggested that an online discussion may enhance nursing staff’s participation in web-based learning, and further facilitate their comments on negative factors. The findings can highly promote nursing staff’s attitudes and practices toward preventing occupational hazards through web-based learning. PMID:25514154

  2. High-risk occupations for suicide.

    PubMed

    Roberts, S E; Jaremin, B; Lloyd, K

    2013-06-01

    High occupational suicide rates are often linked to easy occupational access to a method of suicide. This study aimed to compare suicide rates across all occupations in Britain, how they have changed over the past 30 years, and how they may vary by occupational socio-economic group. Method We used national occupational mortality statistics, census-based occupational populations and death inquiry files (for the years 1979-1980, 1982-1983 and 2001-2005). The main outcome measures were suicide rates per 100 000 population, percentage changes over time in suicide rates, standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs). Several occupations with the highest suicide rates (per 100 000 population) during 1979-1980 and 1982-1983, including veterinarians (ranked first), pharmacists (fourth), dentists (sixth), doctors (tenth) and farmers (thirteenth), have easy occupational access to a method of suicide (pharmaceuticals or guns). By 2001-2005, there had been large significant reductions in suicide rates for each of these occupations, so that none ranked in the top 30 occupations. Occupations with significant increases over time in suicide rates were all manual occupations whereas occupations with suicide rates that decreased were mainly professional or non-manual. Variation in suicide rates that was explained by socio-economic group almost doubled over time from 11.4% in 1979-1980 and 1982-1983 to 20.7% in 2001-2005. Socio-economic forces now seem to be a major determinant of high occupational suicide rates in Britain. As the increases in suicide rates among manual occupations occurred during a period of economic prosperity, carefully targeted suicide prevention initiatives could be beneficial.

  3. Native low-density lipoprotein uptake by macrophage colony-stimulating factor-differentiated human macrophages is mediated by macropinocytosis and micropinocytosis.

    PubMed

    Anzinger, Joshua J; Chang, Janet; Xu, Qing; Buono, Chiara; Li, Yifu; Leyva, Francisco J; Park, Bum-Chan; Greene, Lois E; Kruth, Howard S

    2010-10-01

    To examine the pinocytotic pathways mediating native low-density lipoprotein (LDL) uptake by human macrophage colony-stimulating factor-differentiated macrophages (the predominant macrophage phenotype in human atherosclerotic plaques). We identified the kinase inhibitor SU6656 and the Rho GTPase inhibitor toxin B as inhibitors of macrophage fluid-phase pinocytosis of LDL. Assessment of macropinocytosis by time-lapse microscopy revealed that both drugs almost completely inhibited macropinocytosis, although LDL uptake and cholesterol accumulation by macrophages were only partially inhibited (approximately 40%) by these agents. Therefore, we investigated the role of micropinocytosis in mediating LDL uptake in macrophages and identified bafilomycin A1 as an additional partial inhibitor (approximately 40%) of macrophage LDL uptake that targeted micropinocytosis. When macrophages were incubated with both bafilomycin A1 and SU6656, inhibition of LDL uptake was additive (reaching 80%), showing that these inhibitors target different pathways. Microscopic analysis of fluid-phase uptake pathways in these macrophages confirmed that LDL uptake occurs through both macropinocytosis and micropinocytosis. Our findings show that human macrophage colony-stimulating factor-differentiated macrophages take up native LDL by macropinocytosis and micropinocytosis, underscoring the importance of both pathways in mediating LDL uptake by these cells.

  4. Avian macrophage: effector functions in health and disease.

    PubMed

    Qureshi, M A; Heggen, C L; Hussain, I

    2000-01-01

    Monocytes-macrophages, cells belonging to the mononuclear phagocytic system, are considered as the first line of immunological defense. Being mobile scavenger cells, macrophages participate in innate immunity by serving as phagocytic cells. These cells arise in the bone marrow and subsequently enter the blood circulation as blood monocytes. Upon migration to various tissues, monocytes mature and differentiate into tissue macrophages. Macrophages then initiate the 'acquired' immune response in their capacity as antigen processing and presenting cells. While responding to their tissue microenvironment or exogenous antigenic challenge, macrophages may secrete several immunoregulatory cytokines or metabolites. Being the first line of immunological defense, macrophages therefore represent an important step during interaction with infectious agents. The outcome of the macrophage-pathogen interaction depends upon several factors including the stage of macrophage activation, the nature of the infectious agent, the level of genetic control on macrophage function as well as environmental and nutritional factors that may modulate macrophage activation and functions. Research in avian macrophages has lagged behind that in mammals. This has been largely due to the lack of harvestable resident macrophages from the chicken peritoneal cavity. However, the development of elicitation protocols to harvest inflammatory abdominal macrophages and the availability of transformed chicken macrophage cell lines, has enabled researchers to address several questions related to chicken macrophage biology and function in health and disease. In this manuscript the basic profiles of several macrophage effector functions are described. In addition, the interaction of macrophages with various pathogens as well as the effect of genetic and environmental factors on macrophage functional modulation is described.

  5. Granulocyte-macrophage colony-stimulating factor primes interleukin-13 production by macrophages via protease-activated receptor-2.

    PubMed

    Aoki, Manabu; Yamaguchi, Rui; Yamamoto, Takatoshi; Ishimaru, Yasuji; Ono, Tomomichi; Sakamoto, Arisa; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

    2015-04-01

    Chronic inflammation is often linked to the presence of type 2-polarized macrophages, which are induced by the T helper type 2 cytokines interleukin-4 and interleukin-13 (IL-13). IL-13 is a key mediator of tissue fibrosis caused by T helper type 2-based inflammation. Human neutrophil elastase (HNE) plays a pivotal role in the pathogenesis of pulmonary fibrosis. This study investigated the priming effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on IL-13 expression by macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. Expression of IL-13 mRNA and protein by GM-CSF-dependent macrophages was investigated after stimulation with HNE, using the polymerase chain reaction and enzyme-linked immunosorbent assay. GM-CSF had a priming effect on IL-13 mRNA and protein expression by macrophages stimulated with HNE, while this effect was not observed for various other cytokines. GM-CSF-dependent macrophages showed a significant increase in the expression of protease activated receptor-2 (PAR-2) mRNA and protein. The response of IL-13 mRNA to HNE was significantly decreased by pretreatment with alpha1-antitrypsin, a PAR-2 antibody (SAM11), or a PAR-2 antagonist (ENMD-1068). These findings suggest that stimulation with HNE can induce IL-13 production by macrophages, especially GM-CSF-dependent macrophages. Accordingly, neutrophil elastase may have a key role in fibrosis associated with chronic inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Cardiac macrophages promote diastolic dysfunction.

    PubMed

    Hulsmans, Maarten; Sager, Hendrik B; Roh, Jason D; Valero-Muñoz, María; Houstis, Nicholas E; Iwamoto, Yoshiko; Sun, Yuan; Wilson, Richard M; Wojtkiewicz, Gregory; Tricot, Benoit; Osborne, Michael T; Hung, Judy; Vinegoni, Claudio; Naxerova, Kamila; Sosnovik, David E; Zile, Michael R; Bradshaw, Amy D; Liao, Ronglih; Tawakol, Ahmed; Weissleder, Ralph; Rosenzweig, Anthony; Swirski, Filip K; Sam, Flora; Nahrendorf, Matthias

    2018-02-05

    Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging and heart failure with preserved ejection fraction, remain unclear. Here we show that cardiac macrophages expand in humans and mice with diastolic dysfunction, which in mice was induced by either hypertension or advanced age. A higher murine myocardial macrophage density results from monocyte recruitment and increased hematopoiesis in bone marrow and spleen. In humans, we observed a parallel constellation of hematopoietic activation: circulating myeloid cells are more frequent, and splenic 18 F-FDG PET/CT imaging signal correlates with echocardiographic indices of diastolic dysfunction. While diastolic dysfunction develops, cardiac macrophages produce IL-10, activate fibroblasts, and stimulate collagen deposition, leading to impaired myocardial relaxation and increased myocardial stiffness. Deletion of IL-10 in macrophages improves diastolic function. These data imply expansion and phenotypic changes of cardiac macrophages as therapeutic targets for cardiac fibrosis leading to diastolic dysfunction. © 2018 Hulsmans et al.

  7. Occupational zoonoses in animal husbandry and related activities.

    PubMed

    Battelli, Giorgio; Baldelli, Raffaella; Ghinzelli, Massimo; Mantovani, Adriano

    2006-01-01

    The fact that people working with animals or their products may contract some infections has been known for centuries, before the introduction of the concept of zoonoses. Only recently, at least in Italy, was the prevention of occupational risks taken into account by legislation in spite of the fact that some zoonoses of livestock are of noticeable socio-economic importance. Nowadays some factors such as new production technologies, trade globalization, movements of people, changes in working conditions, are generating new zoonotic and occupational risks, some of which are considered re-emerging. The prevention of occupational zoonoses must be implemented jointly by both veterinary and medical services through prevention and epidemiological surveillance of human and animal health, risk evaluation, diagnosis of infections and working safety. Hopefully, we expect that in the future there will be better interdisciplinary collaboration and that legislation be timely tailored to the need to safeguard working health and safety.

  8. Occupational physical activity assessment for chronic disease prevention and management: A review of methods for both occupational health practitioners and researchers.

    PubMed

    Scott, Kenneth A; Browning, Raymond C

    2016-01-01

    Occupational physical activity (OPA) is an occupational exposure that impacts worker health. OPA is amenable to measurement and modification through the hierarchy of controls. Occupational exposure scientists have roles in addressing inadequate physical activity, as well as excessive or harmful physical activity. Occupational health researchers can contribute to the development of novel OPA exposure assessment techniques and to epidemiologic studies examining the health impacts of physical activity at work. Occupational health practitioners stand to benefit from understanding the strengths and limitations of physical activity measurement approaches, such as accelerometers in smartphones, which are already ubiquitous in many workplaces and in some worksite health programs. This comprehensive review of the literature provides an overview of physical activity monitoring for occupational exposure scientists. This article summarizes data on the public health implications of physical activity at work, highlighting complex relationships with common chronic diseases. This article includes descriptions of several techniques that have been used to measure physical activity at work and elsewhere, focusing in detail on pedometers, accelerometers, and Global Positioning System technology. Additional subjective and objective measurement strategies are described as well.

  9. Macrophages and cellular immunity in Drosophila melanogaster.

    PubMed

    Gold, Katrina S; Brückner, Katja

    2015-12-01

    The invertebrate Drosophila melanogaster has been a powerful model for understanding blood cell development and immunity. Drosophila is a holometabolous insect, which transitions through a series of life stages from embryo, larva and pupa to adulthood. In spite of this, remarkable parallels exist between Drosophila and vertebrate macrophages, both in terms of development and function. More than 90% of Drosophila blood cells (hemocytes) are macrophages (plasmatocytes), making this highly tractable genetic system attractive for studying a variety of questions in macrophage biology. In vertebrates, recent findings revealed that macrophages have two independent origins: self-renewing macrophages, which reside and proliferate in local microenvironments in a variety of tissues, and macrophages of the monocyte lineage, which derive from hematopoietic stem or progenitor cells. Like vertebrates, Drosophila possesses two macrophage lineages with a conserved dual ontogeny. These parallels allow us to take advantage of the Drosophila model when investigating macrophage lineage specification, maintenance and amplification, and the induction of macrophages and their progenitors by local microenvironments and systemic cues. Beyond macrophage development, Drosophila further serves as a paradigm for understanding the mechanisms underlying macrophage function and cellular immunity in infection, tissue homeostasis and cancer, throughout development and adult life. Copyright © 2016. Published by Elsevier Ltd.

  10. Occupation and suicide: Colorado, 2004-2006.

    PubMed

    Stallones, Lorann; Doenges, Timothy; Dik, Bryan J; Valley, Morgan A

    2013-11-01

    Occupation has been identified as a risk factor for suicide. Changes in work environments over time suggest occupations at high risk of suicide may also change. Therefore, periodic examination of suicide by occupation is warranted. The purpose of this article is to describe suicide rates by occupation, sex, and means used in Colorado for the period 2004-2006. To provide information useful in designing suicide prevention programs, the methods used in suicide across occupational groups also are examined. Data from the Colorado Violent Death Reporting System (COVDRS) were obtained for suicides that occurred between 2004 and 2006. Denominators to calculate rates by age, sex, and race used are from the 2000 US Census of the Population data. Men had higher suicide rates than women in all occupation categories except computers and mathematics. Among men, those in farming, fishing, and forestry (475.6 per 100,000) had the highest age-adjusted suicide rates. Among women, workers with the highest suicide rates were in construction and extraction (134.3 per 100,000). The examination of lethal means showed that workers in farming, fishing, and forestry had higher rates of suicide by firearms (50.18 per 100,000) compared with other workers. Healthcare practitioners and technicians had the highest rate of suicide by poisoning (14.25 per 100,000). Workers involved in construction and extraction (26.43 per 100,000) had higher rates of suicide by hanging, suffocation, or strangling. Significant differences in means of suicide were seen by occupation, which could guide future suicide prevention interventions that may decrease work-related suicide risks. Copyright © 2013 Wiley Periodicals, Inc.

  11. Occupational Heat Stress and Kidney Health: From Farms to Factories.

    PubMed

    Nerbass, Fabiana B; Pecoits-Filho, Roberto; Clark, William F; Sontrop, Jessica M; McIntyre, Christopher W; Moist, Louise

    2017-11-01

    Millions of workers around the world are exposed to high temperatures, intense physical activity, and lax labor practices that do not allow for sufficient rehydration breaks. The extent and consequences of heat exposure in different occupational settings, countries, and cultural contexts is not well studied. We conducted an in-depth review to examine the known effects of occupational heat stress on the kidney. We also examined methods of heat-stress assessment, strategies for prevention and mitigation, and the economic consequences of occupational heat stress. Our descriptive review summarizes emerging evidence that extreme occupational heat stress combined with chronic dehydration may contribute to the development of CKD and ultimately kidney failure. Rising global temperatures, coupled with decreasing access to clean drinking water, may exacerbate the effects of heat exposure in both outdoor and indoor workers who are exposed to chronic heat stress and recurrent dehydration. These changes create an urgent need for health researchers and industry to identify work practices that contribute to heat-stress nephropathy, and to test targeted, robust prevention and mitigation strategies. Preventing occupational heat stress presents a great challenge for a concerted multidisciplinary effort from employers, health authorities, engineers, researchers, and governments.

  12. Estimation of benefit of prevention of occupational cancer for comparative risk assessment: methods and examples.

    PubMed

    Lee, Lukas Jyuhn-Hsiarn; Chang, Yu-Yin; Liou, Saou-Hsing; Wang, Jung-Der

    2012-08-01

    To quantify the life years gained and financial savings by preventing a case of occupational cancer. The authors retrieved data from the Taiwan Cancer Registry and linked them with the National Mortality Registry to estimate the survival functions for major occupational cancers: lung, pleural mesothelioma, urinary bladder and leukaemia. Assuming a constant excess hazard for each type of cancer, the authors extrapolated lifetime survival functions by the Monte Carlo method. For each patient with cancer, the authors simulated an age- and gender-matched person without cancer based on vital statistics of Taiwan to estimate life expectancy and expected years of life lost (EYLL). By using the reimbursement data from the National Health Insurance Research Database, the authors calculated the average monthly healthcare expenditures, which were summed to estimate the lifetime healthcare expenditures after adjusting for the corresponding monthly survival probability. A total of 51,408, 136, 12,891 and 5285 new cases of lung, pleural mesothelioma, bladder and leukaemia cancers, respectively, were identified during 1997-2005 and followed until the end of 2007. The EYLL was predicted to be 13.7±0.1, 18.9±0.7, 4.7±0.3 and 19.4±0.5 years for these cancers, respectively, and the lifetime healthcare expenditures with a 3% annual discount were predicted to be US$22,359, US$14,900, US$51,987 and US$59,741, respectively. The burden of these occupational cancers, in terms of EYLL and lifetime healthcare expenditures, was substantial. Such estimates may provide useful empirical evidence for comparative risk assessment that can be applied in health policy-making and clinical decision-making.

  13. Strategy for Coordinated EPA/Occupational Safety and Health Administration (OSHA) Implementation of the Chemical Accident Prevention Requirements of the Clean Air Act Amendments of 1990

    EPA Pesticide Factsheets

    EPA and the Occupational Safety and Health Administration (OSHA) share responsibility for prevention: OSHA has the Process Safety Management Standard to protect workers, and EPA the Risk Management Program to protect the general public and environment.

  14. Development of contrast agents targeted to macrophage scavenger receptors for MRI of vascular inflammation

    PubMed Central

    Gustafsson, Björn; Youens, Susan; Louie, Angelique Y.

    2008-01-01

    Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial diseases through early diagnosis, there is a need for methods to image arteries in the sub-clinical stage as well as clinical stage using various non-invasive techniques, including Magnetic Resonance Imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted towards vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI. PMID:16536488

  15. Heparanase induced by advanced glycation end products (AGEs) promotes macrophage migration involving RAGE and PI3K/AKT pathway

    PubMed Central

    2013-01-01

    Background Advanced glycation end products (AGEs), inflammatory-associated macrophage migration and accumulation are crucial for initiation and progression of diabetic vascular complication. Enzymatic activity of heparanase (HPA) is implicated strongly in dissemination of metastatic tumor cells and cells of the immune system. In addition, HPA enhances the phosphorylation of selected signaling molecules including AKT pathway independent of enzymatic activity. However, virtually nothing is presently known the role of HPA during macrophage migration exposed to AGEs involving signal pathway. Methods These studies were carried out in Ana-1 macrophages. Macrophage viability was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. HPA and AKT protein expression in macrophages are analysed by Western blotting and HPA mRNA expression by real time quantitative RT-PCR. Release of HPA was determined by ELISA. Macrophage migration was assessed by Transwell assays. Results HPA protein and mRNA were found to be increased significantly in AGEs-treated macrophages. Pretreatment with anti-HPA antibody which recognizes the nonenzymatic terminal of HPA prevented AGEs-induced AKT phosphorylation and macrophage migration. LY294002 (PI3k/AKT inhibitor) inhibited AGEs-induced macrophage migration. Furthermore, pretreatment with anti-receptor for advanced glycation end products (RAGE) antibody attenuated AGEs-induced HPA expression, AKT phosphorylation and macrophage migration. Conclusions These data indicate that AGEs-induced macrophage migration is dependent on HPA involving RAGE-HPA-PI3K/AKT pathway. The nonenzymatic activity of HPA may play a key role in AGEs-induced macrophage migration associated with inflammation in diabetic vascular complication. PMID:23442498

  16. Spatial Clustering of Occupational Injuries in Communities

    PubMed Central

    Friedman, Lee; Chin, Brian; Madigan, Dana

    2015-01-01

    Objectives. Using the social-ecological model, we hypothesized that the home residences of injured workers would be clustered predictably and geographically. Methods. We linked health care and publicly available datasets by home zip code for traumatically injured workers in Illinois from 2000 to 2009. We calculated numbers and rates of injuries, determined the spatial relationships, and developed 3 models. Results. Among the 23 200 occupational injuries, 80% of cases were located in 20% of zip codes and clustered in 10 locations. After component analysis, numbers and clusters of injuries correlated directly with immigrants; injury rates inversely correlated with urban poverty. Conclusions. Traumatic occupational injuries were clustered spatially by home location of the affected workers and in a predictable way. This put an inequitable burden on communities and provided evidence for the possible value of community-based interventions for prevention of occupational injuries. Work should be included in health disparities research. Stakeholders should determine whether and how to intervene at the community level to prevent occupational injuries. PMID:25905838

  17. Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages

    NASA Astrophysics Data System (ADS)

    Freire-de-Lima, Célio G.; Nascimento, Danielle O.; Soares, Milena B. P.; Bozza, Patricia T.; Castro-Faria-Neto, Hugo C.; de Mello, Fernando G.; Dosreis, George A.; Lopes, Marcela F.

    2000-01-01

    After apoptosis, phagocytes prevent inflammation and tissue damage by the uptake and removal of dead cells. In addition, apoptotic cells evoke an anti-inflammatory response through macrophages. We have previously shown that there is intense lymphocyte apoptosis in an experimental model of Chagas' disease, a debilitating cardiac illness caused by the protozoan Trypanosoma cruzi. Here we show that the interaction of apoptotic, but not necrotic T lymphocytes with macrophages infected with T. cruzi fuels parasite growth in a manner dependent on prostaglandins, transforming growth factor-β (TGF-β) and polyamine biosynthesis. We show that the vitronectin receptor is critical, in both apoptotic-cell cytoadherence and the induction of prostaglandin E2/TGF-β release and ornithine decarboxylase activity in macrophages. A single injection of apoptotic cells in infected mice increases parasitaemia, whereas treatment with cyclooxygenase inhibitors almost completely ablates it in vivo. These results suggest that continual lymphocyte apoptosis and phagocytosis of apoptotic cells by macrophages have a role in parasite persistence in the host, and that cyclooxygenase inhibitors have potential therapeutic application in the control of parasite replication and spread in Chagas' disease.

  18. Iron Reduces M1 Macrophage Polarization in RAW264.7 Macrophages Associated with Inhibition of STAT1.

    PubMed

    Gan, Zhen-Shun; Wang, Qian-Qian; Li, Jia-Hui; Wang, Xu-Liang; Wang, Yi-Zhen; Du, Hua-Hua

    2017-01-01

    Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions. The aim of this study is to investigate the cross-regulatory interactions between M1 macrophage polarization and iron metabolism. Firstly, we characterized the transcription of genes related to iron homeostasis in M1 RAW264.7 macrophages stimulated by IFN- γ . The molecular signature of M1 macrophages showed high levels of iron storage (ferritin), a low level of iron export (ferroportin), and changes of iron regulators (hepcidin and transferrin receptors), which favour iron sequestration in the reticuloendothelial system and are benefit for inflammatory disorders. Then, we evaluated the effect of iron on M1 macrophage polarization. Iron significantly reduced mRNA levels of IL-6, IL-1 β , TNF- α , and iNOS produced by IFN- γ -polarized M1 macrophages. Immunofluorescence analysis showed that iron also reduced iNOS production. However, iron did not compromise but enhanced the ability of M1-polarized macrophages to phagocytose FITC-dextran. Moreover, we demonstrated that STAT1 inhibition was required for reduction of iNOS and M1-related cytokines production by the present of iron. Together, these findings indicated that iron decreased polarization of M1 macrophages and inhibited the production of the proinflammatory cytokines. The results expanded our knowledge about the role of iron in macrophage polarization.

  19. [Occupational risk related to optical radiation exposure in construction workers].

    PubMed

    Gobba, F; Modenese, A

    2012-01-01

    Optical Radiation is a relevant occupational risk in construction workers, mainly as a consequence of the exposure to the ultraviolet (UV) component of solar radiation (SR). Available data show that UV occupational limits are frequently exceeded in these workers, resulting in an increased occupational risk of various acute and chronic effects, mainly to skin and to the eye. One of the foremost is the carcinogenic effect: SR is indeed included in Group 1 IARC (carcinogenic to humans). UV exposure is related to an increase of the incidence of basal cell carcinoma, squamous cell carcinoma of the skin and cutaneous malignant melanoma (CMM). The incidence of these tumors, especially CMM, is constantly increasing in Caucasians in the last 50 years. As a conclusion, an adequate evaluation of the occupational risk related to SR, and adequate preventive measures are essential in construction workers. The role of occupational physicians in prevention is fundamental.

  20. Epidemiologic characteristics of compensated occupational lung cancers among Korean workers.

    PubMed

    Ahn, Yeon-Soon; Jeong, Kyoung Sook

    2014-11-01

    An understanding of the characteristics of occupational lung cancer is important to establish policies that prevent carcinogen exposure and to compensate workers exposed to lung carcinogens. This study analyzed the characteristics of occupational lung cancers in workers who were compensated under the Industrial Accident Compensation Insurance Law between 1994 and 2011. A total of 179 occupational lung cancers were compensated. The main carcinogenic exposure was asbestos, followed by crystalline silica and hexavalent chromium. The mean exposure duration and latency were 19.8 and 23.2 yr. The most common industry was manufacturing, followed by construction and transportation. The most common occupation was maintenance and repair, followed by foundry work, welding, painting, and spinning or weaving. Although asbestos was predominant carcinogen, the proportion of these cases was relatively low compared to other developed countries. Proper surveillance system is needed to monitor occupational lung cancer and improve prevention measures.

  1. Occupational safety and health objectives of Healthy People 2010: a systematic approach for occupational health nurses--Part II.

    PubMed

    Olszewski, Kimberly; Parks, Carol; Chikotas, Noreen E

    2007-03-01

    Occupational safety and health objectives 20.6 through 20.11 focus on reducing work-related assaults, lead exposure, skin diseases and disorders, needlestick injuries, and work-related, noise-induced hearing loss and promoting worksite stress reduction programs. Using the intervention strategies provided, occupational health nurses can play a key role in reducing workplace-related injury, disease, disability, and death. variety of resources pertaining to occupational health and safety from the federal, national, health care, nursing, and environmental realms can assist occupational health nurses in developing and implementing programs appropriate for their workplaces. Through the Healthy People 2010 occupational health and safety objectives, occupational health nurses have the opportunity to develop and implement workplace policies and programs promoting not only a safe and healthy work environment but also improved health and disease prevention. Occupational health nurses can implement strategies to increase quality and years of life and eliminate health disparities in the American work force.

  2. The macrophage marker translocator protein (TSPO) is down-regulated on pro-inflammatory 'M1' human macrophages.

    PubMed

    Narayan, Nehal; Mandhair, Harpreet; Smyth, Erica; Dakin, Stephanie Georgina; Kiriakidis, Serafim; Wells, Lisa; Owen, David; Sabokbar, Afsie; Taylor, Peter

    2017-01-01

    The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis. Here, we utilized three human sources of monocyte derived macrophages (MDM), from THP-1 monocytes, healthy peripheral blood monocytes and synovial fluid monocytes from patients with rheumatoid arthritis, to undertake a detailed investigation of TSPO expression in activated macrophages. In this work, we demonstrate a consistent down-regulation of TSPO mRNA and protein in macrophages activated to a pro-inflammatory, or 'M1' phenotype. Conversely, stimulation of macrophages to an M2 phenotype with IL-4, dexamethasone or TGF-β1 did not alter TSPO expression, regardless of MDM source. The reasons for this are uncertain, but our study findings add some supporting evidence for recent investigations concluding that TSPO may be involved in negative regulation of inflammatory responses in macrophages.

  3. International survey of occupational health nurses' roles in multidisciplinary teamwork in occupational health services.

    PubMed

    Rogers, Bonnie; Kono, Keiko; Marziale, Maria Helena Palucci; Peurala, Marjatta; Radford, Jennifer; Staun, Julie

    2014-07-01

    Access to occupational health services for primary prevention and control of work-related injuries and illnesses by the global workforce is limited (World Health Organization [WHO], 2013). From the WHO survey of 121 (61%) participating countries, only one-third of the responding countries provided occupational health services to more than 30% of their workers (2013). How services are provided in these countries is dependent on legal requirements and regulations, population, workforce characteristics, and culture, as well as an understanding of the impact of workplace hazards and worker health needs. Around the world, many occupational health services are provided by occupational health nurses independently or in collaboration with other disciplines' professionals. These services may be health protection, health promotion, or both, and are designed to reduce health risks, support productivity, improve workers' quality of life, and be cost-effective. Rantanen (2004) stated that basic occupational health services must increase rather than decline, especially as work becomes more complex; workforces become more dynamic and mobile, creating new models of work-places; and jobs become more precarious and temporary. To better understand occupational health services provided by occupational health nurses globally and how decisions are made to provide these services, this study examined the scope of services provided by a sample of participating occupational health nurses from various countries. Copyright 2014, SLACK Incorporated.

  4. Tumor necrosis factor-α-dependent infiltration of macrophages into the dorsal root ganglion in a rat disc herniation model.

    PubMed

    You, Changcheng; Zhu, Kai; Liu, Xiaoqi; Xi, Chunyang; Zhang, Zhipeng; Xu, Gongping; Yan, Jinglong

    2013-11-01

    A prospective molecular mechanism of macrophages infiltration in experimental disc herniation. To investigate the mechanisms of macrophages infiltration into the dorsal root ganglion (DRG) in a rat model of disc herniation. Macrophages infiltrate the DRG after application of nucleus pulposus (NP) on the DRG, and may play an important role in radiculopathy. However, the mechanisms of macrophages infiltration after NP application remain poorly understood. After experimental disc herniation in this study, we investigated changes in the expression of ED1 (a marker of macrophages) and vascular cell adhesion molecule-1 (VCAM-1) in DRG using immunofluorescence. We also investigated the expression of ED1 and VCAM-1 in DRG by treatment with tumor necrosis factor-α (TNF-α) inhibitor at the time of surgery. We found a massive ED1-positive macrophages infiltrated the DRG, and VCAM-1-like immunoreactivity vessels became evident after NP application. Furthermore, both macrophage infiltration and VCAM-1 expression were prevented by treatment with TNF-α inhibitor at the time of surgery. These findings indicated that macrophages infiltration into the DRG was TNF-α-dependent, and might be partly mediated by VCAM-1 in the early stage of experimental lumbar disc herination. Taken together, this study provides important preliminary data suggesting that TNF-α plays an important role in the macrophage infiltration. N/A.

  5. Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation

    PubMed Central

    Tomlinson, Gareth H.; Miles, Katherine; Smith, Richard W. P.; Rossi, Adriano G.; Hiemstra, Pieter S.; van ’t Wout, Emily F. A.; Dean, Jonathan L. E.; Gray, Nicola K.; Lu, Wuyuan; Gray, Mohini

    2016-01-01

    Neutrophils are the first and most numerous cells to arrive at the site of an inflammatory insult and are among the first to die. We previously reported that alpha defensins, released from apoptotic human neutrophils, augmented the antimicrobial capacity of macrophages while also inhibiting the biosynthesis of proinflammatory cytokines. In vivo, alpha defensin administration protected mice from inflammation, induced by thioglychollate-induced peritonitis or following infection with Salmonella enterica serovar Typhimurium. We have now dissected the antiinflammatory mechanism of action of the most abundant neutrophil alpha defensin, Human Neutrophil Peptide 1 (HNP1). Herein we show that HNP1 enters macrophages and inhibits protein translation without inducing the unfolded-protein response or affecting mRNA stability. In a cell-free in vitro translation system, HNP1 powerfully inhibited both cap-dependent and cap-independent mRNA translation while maintaining mRNA polysomal association. This is, to our knowledge, the first demonstration of a peptide released from one cell type (neutrophils) directly regulating mRNA translation in another (macrophages). By preventing protein translation, HNP1 functions as a “molecular brake” on macrophage-driven inflammation, ensuring both pathogen clearance and the resolution of inflammation with minimal bystander tissue damage. PMID:27044108

  6. Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization: lessons and open questions.

    PubMed

    Mantovani, Alberto; Locati, Massimo

    2013-07-01

    Macrophages are present in all body compartments, including cancerous tissues, and their functions are profoundly affected by signals from the microenvironment under homeostatic and pathological conditions. Tumor-associated macrophages are a major cellular component of cancer-related inflammation and have served as a paradigm for the plasticity and functional polarization of mononuclear phagocytes. Tumor-associated macrophages can exert dual influence of cancer depending on the activation state, with classically activated (M1) and alternatively activated (M2) cells generally exerting antitumoral and protumoral functions, respectively. These are extremes in a continuum of polarization states in a universe of diversity. Tumor-associated macrophages affect virtually all aspects of tumor tissues, including stem cells, metabolism, angiogenesis, invasion, and metastasis. Progress has been made in defining signaling molecules, transcription factors, epigenetic changes, and repertoire of microRNAs underlying macrophage polarization. Preclinical and early clinical data suggest that macrophages may serve as tools for the development of innovative diagnostic and therapeutic strategies in cancer and chronic nonresolving inflammatory diseases.

  7. Developmental origin of lung macrophage diversity

    PubMed Central

    Tan, Serena Y. S.; Krasnow, Mark A.

    2016-01-01

    Macrophages are specialized phagocytic cells, present in all tissues, which engulf and digest pathogens, infected and dying cells, and debris, and can recruit and regulate other immune cells and the inflammatory response and aid in tissue repair. Macrophage subpopulations play distinct roles in these processes and in disease, and are typically recognized by differences in marker expression, immune function, or tissue of residency. Although macrophage subpopulations in the brain have been found to have distinct developmental origins, the extent to which development contributes to macrophage diversity between tissues and within tissues is not well understood. Here, we investigate the development and maintenance of mouse lung macrophages by marker expression patterns, genetic lineage tracing and parabiosis. We show that macrophages populate the lung in three developmental waves, each giving rise to a distinct lineage. These lineages express different markers, reside in different locations, renew in different ways, and show little or no interconversion. Thus, development contributes significantly to lung macrophage diversity and targets each lineage to a different anatomical domain. PMID:26952982

  8. [Cost-benefit analysis of practical occupational medicine service].

    PubMed

    Kentner, M

    1996-02-01

    Cost problems in business, industry and government service force everyone to probe into the economy of traditional patterns of work and procedures. Occupational medicine is no exception. However, there has been a lack of criteria for assessing the economic aspects of occupational medicine. We are therefore suggesting an approach. Caring for the "human capital" factor is a cornerstone of free socioeconomy. Workers should not only be suitably qualified for their job but there must be the smallest possible minimum of absenteeism. Occupational medicine can do something to positively influence the following factors: by preventing incapacity to work by preventing job accidents and professional diseases by reducing the time required to cover distances between or within workflow phases or stages by reducing waste of time by waiting. Model calculations, based on highly plausible basic postulates, show that fully integrated occupational medical services are throughout economic and cost-saving. Using a concrete example, we arrived at a cost/benefit ratio of 1:2 while confining ourselves to benefits attainable within a relatively short time. We ignored other, future benefits requiring certain preventive measures, as well as other parameters that are difficult to assess, such as corporate identity. At present occupational medicine faces a certain amount of identity crisis which should not be counteracted by pointing to legislation that justifies its existence, but rather by proving that it is indeed highly economical because it saves time and money.

  9. Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis

    PubMed Central

    Martínez, María Sofía; Palmar, Jim; Bautista, Jordan; Chávez-Castillo, Mervin; Gómez, Alexis; Bermúdez, Valmore

    2015-01-01

    Cardiovascular disease (CVD) is a global epidemic, currently representing the worldwide leading cause of morbidity and mortality. Atherosclerosis is the fundamental pathophysiologic component of CVD, where the immune system plays an essential role. Monocytes and macrophages are key mediators in this aspect: due to their heterogeneity and plasticity, these cells may act as either pro- or anti-inflammatory mediators. Indeed, monocytes may develop heterogeneous functional phenotypes depending on the predominating pro- or anti-inflammatory microenvironment within the lesion, resulting in classic, intermediate, and non-classic monocytes, each with strikingly differing features. Similarly, macrophages may also adopt heterogeneous profiles being mainly M1 and M2, the former showing a proinflammatory profile while the latter demonstrates anti-inflammatory traits; they are further subdivided in several subtypes with more specialized functions. Furthermore, macrophages may display plasticity by dynamically shifting between phenotypes in response to specific signals. Each of these distinct cell profiles is associated with diverse biomarkers which may be exploited for therapeutic intervention, including IL-10, IL-13, PPAR-γ, LXR, NLRP3 inflammasomes, and microRNAs. Direct modulation of the molecular pathways concerning these potential macrophage-related targets represents a promising field for new therapeutic alternatives in atherosclerosis and CVD. PMID:26491604

  10. The current status of occupational health in China

    PubMed Central

    Zhang, Xueyan; Li, Tao

    2010-01-01

    Objective This study aimed to summarize the major health problems among Chinese workers, the strategies and measures for occupational hazards control, the network and organizations of occupational health administration, and the achievements and current challenges of occupational health in China. Results The situation of occupational health was found to be still serious in China. Enterprises with occupational hazards were widely distributed, the exposed population and cases of occupational diseases were numerous, and occupational risks were being transferred from the city to the countryside and from developed areas to developing ones. New emerging problems coexisted with traditional occupational hazards. Besides, a lack of occupational health services for migrant workers could be a major problem for a long time. Conclusions It is necessary to improve the fields related to occupational health, such as the supervision and administration of small- and medium-scale enterprises, research into key techniques for the prevention and control of occupational hazards, systems for the diagnosis and reporting of occupational diseases, and the training of health professionals. PMID:21432554

  11. Occupational Health and the Arts.

    PubMed

    Hinkamp, David L; McCann, Michael; Babin, Angela

    2017-09-01

    Work in the visual arts, performing arts, and writing can involve exposures to occupational hazards, including hazardous materials, equipment, and conditions, but few art workplaces have strong occupational health resources. Literature searches were conducted for articles that illustrate these concerns. Medical databases were searched for art-related health articles. Other sources were also reviewed, including, unindexed art-health publications, and popular press articles. Information was located that described some exposed populations, art-related hazards, and resulting disorders. Anecdotal reports were used when more complete data were not available. Health hazards in the arts are significant. Occupational health professionals are familiar with most of these concerns and understand their treatment and prevention. The occupational health approach can reduce the health hazards encountered by at-risk art workers. Additional research would benefit these efforts. Resources for further information are available.

  12. Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages.

    PubMed

    Soldano, Stefano; Pizzorni, Carmen; Paolino, Sabrina; Trombetta, Amelia Chiara; Montagna, Paola; Brizzolara, Renata; Ruaro, Barbara; Sulli, Alberto; Cutolo, Maurizio

    2016-01-01

    Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBM-derived macrophages compared to M0-controls and untreated cells. In cultured PBM-derived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were

  13. Yersinia pestis and host macrophages: immunodeficiency of mouse macrophages induced by YscW.

    PubMed

    Bi, Yujing; Du, Zongmin; Han, Yanping; Guo, Zhaobiao; Tan, Yafang; Zhu, Ziwen; Yang, Ruifu

    2009-09-01

    The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system (T3SS) that transfers six Yersinia outer protein (Yop) effector proteins into the cytoplasm of eukaryotic cells, leading to disruption of host defence mechanisms. It is shown in this study that Yersinia pestis YscW, a protein of the T3SS injectisome, contributes to the induction of a deficiency in phagocytosis in host macrophages and a reduction in their antigen-presenting capacity. A Y. pestis strain lacking yscW had no effect on uptake by host macrophages. In mice infected with wild-type Y. pestis, the yscW mutant or a complement strain, immunodeficiency was observed in host macrophages compared with those from uninfected mice. However, the phagocytosis and antigen presenting capacities of macrophages infected by yscW mutant strain both in vivo and in vitro were significantly higher than those by wild type strain. Consistent with this finding, when YscW was expressed in the RAW264.7 macrophage cell line, phagocytosis and antigen-presenting capacities were significantly lower than those of the control groups. These results indicate that Y. pestis YscW may directly induce immunodeficiency in murine macrophages by crippling their phagocytosis and antigen-presenting capacities. These data provide evidences to Y. pestis pathogenesis that some proteins in T3SS injectisome, such as YscW protein, might play independent roles in disrupting host defense apart from their known functions.

  14. Mimicking the tumor microenvironment to regulate macrophage phenotype and assessing chemotherapeutic efficacy in embedded cancer cell/macrophage spheroid models.

    PubMed

    Tevis, Kristie M; Cecchi, Ryan J; Colson, Yolonda L; Grinstaff, Mark W

    2017-03-01

    Tumor associated macrophages (TAMs) are critical stromal components intimately involved with the progression, invasion, and metastasis of cancer cells. To address the need for an in vitro system that mimics the clinical observations of TAM localizations and subsequent functional performance, a cancer cell/macrophage spheroid model is described. The central component of the model is a triple negative breast cancer spheroid embedded in a three-dimensional collagen gel. Macrophages are incorporated in two different ways. The first is a heterospheroid, a spheroid containing both tumor cells and macrophages. The heterospheroid mimics the population of TAMs infiltrated into the tumor mass, thus being exposed to hypoxia and metabolic gradients. In the second model, macrophages are diffusely seeded in the collagen surrounding the spheroid, thus modeling TAMs in the cancer stroma. The inclusion of macrophages as a heterospheroid changes the metabolic profile, indicative of synergistic growth. In contrast, macrophages diffusely seeded in the collagen bear the same profile regardless of the presence of a tumor cell spheroid. The macrophages in the heterospheroid secrete EGF, a cytokine critical to tumor/macrophage co-migration, and an EGF inhibitor decreases the metabolic activity of the heterospheroid, which is not observed in the other systems. The increased secretion of IL-10 indicates that the heterospheroid macrophages follow an M2/TAM differentiation pathway. Lastly, the heterospheroid exhibits resistance to paclitaxel. In summary, the collagen embedded heterospheroid model promotes TAM-like characteristics, and will be of utility in cancer biology and drug discovery. Two in vitro collagen-embedded multicellular spheroid models are described that mimic the clinical observations of macrophage localization within a tumor. Incorporation of macrophages within a breast cancer spheroid emphasizes cell-cell interactions with subsequent differentiation toward a tumor

  15. Contribution of job-exposure matrices for exposure assessment in occupational safety and health monitoring systems: application from the French national occupational disease surveillance and prevention network.

    PubMed

    Florentin, Arnaud; Zmirou-Navier, Denis; Paris, Christophe

    2017-08-01

    To detect new hazards ("signals"), occupational health monitoring systems mostly rest on the description of exposures in the jobs held and on reports by medical doctors; these are subject to declarative bias. Our study aims to assess whether job-exposure matrices (JEMs) could be useful tools for signal detection by improving exposure reporting. Using the French national occupational disease surveillance and prevention network (RNV3P) data from 2001 to 2011, we explored the associations between disease and exposure prevalence for 3 well-known pathology/exposure couples and for one debatable couple. We compared the associations measured when using physicians' reports or applying the JEMs, respectively, for these selected diseases and across non-selected RNV3P population or for cases with musculoskeletal disorders, used as two reference groups; the ratio of exposure prevalences according to the two sources of information were computed for each disease category. Our population contained 58,188 subjects referred with pathologies related to work. Mean age at diagnosis was 45.8 years (95% CI 45.7; 45.9), and 57.2% were men. For experts, exposure ratios increase with knowledge on exposure causality. As expected, JEMs retrieved more exposed cases than experts (exposure ratios between 12 and 194), except for the couple silica/silicosis, but not for the MSD control group (ratio between 0.2 and 0.8). JEMs enhanced the number of exposures possibly linked with some conditions, compared to experts' assessment, relative to the whole database or to a reference group; they are less likely to suffer from declarative bias than reports by occupational health professionals.

  16. Occupational injuries in Bahrain.

    PubMed

    al-Arrayed, A; Hamza, A

    1995-10-01

    A study was conducted to show the problem of occupational injuries in Bahrain and try to highlight some solutions that may help to prevent or reduce workplace hazards. The data for occupational injuries between 1988 to 1991 from the social insurance records were reviewed and analysed. The data were summarized, grouped and tabulated according to age, sex, nationality, work place, type of injuries, cause and site of injury. Data were analysed statistically, frequencies were computed and results represented graphically. The study shows that there was a decline in the number of injuries in 1990 and 1991 due to a slow-down of economic activities in general in the Arabian Gulf region during the Gulf War. It also shows that Asian workers are at a high risk of occupational injuries.

  17. The surveillance of occupational diseases in Italy: the MALPROF system.

    PubMed

    Campo, G; Papale, A; Baldasseroni, A; Di Leone, G; Magna, B; Martini, B; Mattioli, S

    2015-11-01

    Occupational diseases data can guide efforts to improve worker's health and safety. To describe MALPROF, the Italian system for surveillance of work-related diseases collected by the subregional Department of Prevention. The MALPROF system started in 1999 with contributions from Lombardy and Tuscany and spread in the following years to collect contributions from 14 out of the 20 Italian regions. MALPROF data were explored to follow-up work-related diseases and to detect emerging occupational health risks by calculating proportional reporting ratio (PRR), as in pharmacosurveillance. It classified work-related diseases according to economic sector and job activity in which the exposure occurred. Occupational physicians of the Italian National Health Service evaluate the possible causal relationship with occupational exposures and store the data in a centralized database. From 1999 to 2012, the MALPROF system collected about 112000 cases of workers' diseases. In 2010, more than 13000 cases of occupational diseases were reported. The most frequently reported diseases were hearing loss (n = 4378, 32%), spine disorders (n = 2394, 17%) and carpal tunnel syndrome (n = 1560, 11%). The PRR calculated for cervical disc herniation, a disease whose occupational origin has to be studied, in 1999-2010 was 2.47 [95% confidence interval (CI) 1.76-3.47] for drivers and 36.64 (95% CI 22.03-60.93) for air transport workers. MALPROF is a sensitive system for identifying possible associations between occupational risks and diseases, it can contribute to the development of preventive measures, to evaluate the effectiveness of preventive interventions and to stimulate research on new occupational risks and diseases. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. The influence of macrophage growth factors on Theiler's Murine Encephalomyelitis Virus (TMEV) infection and activation of macrophages.

    PubMed

    Schneider, Karin M; Watson, Neva B; Minchenberg, Scott B; Massa, Paul T

    2018-02-01

    Macrophages are common targets for infection and innate immune activation by many pathogenic viruses including the neurotropic Theiler's Murine Encephalomyelitis Virus (TMEV). As both infection and innate activation of macrophages are key determinants of viral pathogenesis especially in the central nervous system (CNS), an analysis of macrophage growth factors on these events was performed. C3H mouse bone-marrow cells were differentiated in culture using either recombinant macrophage colony stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), inoculated with TMEV (BeAn) and analyzed at various times thereafter. Cytokine RNA and protein analysis, virus titers, and flow cytometry were performed to characterize virological parameters under these culture conditions. GM-CSF-differentiated macrophages showed higher levels of TMEV viral RNA and proinflammatory molecules compared to infected M-CSF-differentiated cells. Thus, GM-CSF increases both TMEV infection and TMEV-induced activation of macrophages compared to that seen with M-CSF. Moreover, while infectious viral particles decreased from a peak at 12h to undetectable levels at 48h post infection, TMEV viral RNA remained higher in GM-CSF- compared to M-CSF-differentiated macrophages in concert with increased proinflammatory gene expression. Analysis of a possible basis for these differences determined that glycolytic rates contributed to heightened virus replication and proinflammatory cytokine secretion in GM-CSF compared to M-CSF-differentiated macrophages. In conclusion, we provide evidence implicating a role for GM-CSF in promoting virus replication and proinflammatory cytokine expression in macrophages, indicating that GM-CSF may be a key factor for TMEV infection and the induction of chronic TMEV-induced immunopathogenesis in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Social representations of biosecurity in nursing: occupational health and preventive care.

    PubMed

    Sousa, Álvaro Francisco Lopes de; Queiroz, Artur Acelino Francisco Luz Nunes; Oliveira, Layze Braz de; Moura, Maria Eliete Batista; Batista, Odinéa Maria Amorim; Andrade, Denise de

    2016-01-01

    to understand the biosecurity social representations by primary care nursing professionals and analyze how they articulate with quality of care. exploratory and qualitative research based on social representation theory. The study participants were 36 nursing workers from primary health care in a state capital in the Northeast region of Brazil. The data were analyzed by descending hierarchical classification. five classes were obtained: occupational accidents suffered by professionals; occupational exposure to biological agents; biosecurity management in primary health care; the importance of personal protective equipment; and infection control and biosecurity. the different positions taken by the professionals seem to be based on a field of social representations related to the concept of biosecurity, namely exposure to accidents and risks to which they are exposed. However, occupational accidents are reported as inherent to the practice.

  20. [Occupational exposure investigation and protective measures in a tertiary infectious disease hospital].

    PubMed

    Ding, H M; Zhou, X P; Huang, J Z

    2018-02-20

    Objective: To investigate the cause of occupational exposure among 136 nurses in a tertiary infectious disease hospital, and puts forward the prevention strategy. Methods: A total of 136 nurses exposed to occupational exposure between 2014 and 2016 were included in the study. Analysis was conducted from the years of work of nurses, exposure routes, and the pathogens. Results: The nurses suffer from the highest risk of occupational exposures (73.91%) .Nurses working for less than 5 years and interns are most likely to suffer occupational exposure (45.59% and 35.29% respectively) . Occupational exposure was mainly caused by needle injuries, in which infusion was the main route of occupational exposure (36.76%) . The improper treatment of needle pulling after infusion is the main link of needle puncture (36.76%) . Occupational exposure pathogens were mainly HBV (63.24%) . Conclusion: Nursing staff is the high-risk group of occupational exposure. Irregular operation, lack of awareness of protection, improper disposal after the needle withdrawal and poor safety assessment of the operating environment are the main causes of occupational exposure. It is suggested to strengthen the training of occupational safety and protection, enhance clinical nurses occupational safety protection consciousness, standardize medical operation, so as to prevent the occurrence of occupational exposure.

  1. Awareness of occupational skin disease in the service sector.

    PubMed

    Holness, D L; Kudla, I; Brown, J; Miller, S

    2017-06-01

    Occupational skin disease (OSD) is a common occupational disease. Although primary prevention strategies are known, OSDs remain prevalent in a variety of work environments including the service sector (restaurant/food services, retail/wholesale, tourism/hospitality and vehicle sales and service). To obtain information about awareness and prevention of OSD in the service sector. Focus groups and a survey were conducted with two groups. The first consisted of staff of the provincial health and safety association for the service sector and the second group comprised representatives from sector employers. Focus groups highlighted key issues to inform the survey that obtained information about perceptions of awareness and prevention of OSD and barriers to awareness and prevention. Both provincial health and safety association staff and sector employer representatives highlighted low awareness and a low level of knowledge of OSD in the sector. Barriers to awareness and prevention included a low reported incidence of OSD, low priority, lack of training materials, lack of time and cost of training, lack of management support and workplace culture. A starting point for improving prevention of OSD in the service sector is increased awareness. Identification of the barriers to awareness and prevention will help to shape an awareness campaign and prevention strategies. Building on existing experience in Europe will be important. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  2. 24 CFR 35.1345 - Occupant protection and worksite preparation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard Evaluation and Hazard Reduction Activities § 35.1345 Occupant... occupants and the environment from contamination from lead-contaminated or lead-containing materials during...

  3. 24 CFR 35.1345 - Occupant protection and worksite preparation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard Evaluation and Hazard Reduction Activities § 35.1345 Occupant... occupants and the environment from contamination from lead-contaminated or lead-containing materials during...

  4. 24 CFR 35.1345 - Occupant protection and worksite preparation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard Evaluation and Hazard Reduction Activities § 35.1345 Occupant... occupants and the environment from contamination from lead-contaminated or lead-containing materials during...

  5. 24 CFR 35.1345 - Occupant protection and worksite preparation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard Evaluation and Hazard Reduction Activities § 35.1345 Occupant... occupants and the environment from contamination from lead-contaminated or lead-containing materials during...

  6. 24 CFR 35.1345 - Occupant protection and worksite preparation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard Evaluation and Hazard Reduction Activities § 35.1345 Occupant... occupants and the environment from contamination from lead-contaminated or lead-containing materials during...

  7. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Hutter, Gregor; Spitler, Ryan; Lenkov, Olga; Mahmoudi, Morteza; Shaw, Aubie; Pajarinen, Jukka Sakari; Nejadnik, Hossein; Goodman, Stuart; Moseley, Michael; Coussens, Lisa Marie; Daldrup-Link, Heike Elisabeth

    2016-11-01

    Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.

  8. Lymphoid tissue and plasmacytoid dendritic cells and macrophages do not share a common macrophage-dendritic cell-restricted progenitor.

    PubMed

    Sathe, Priyanka; Metcalf, Donald; Vremec, David; Naik, Shalin H; Langdon, Wallace Y; Huntington, Nicholas D; Wu, Li; Shortman, Ken

    2014-07-17

    The relationship between dendritic cells (DCs) and macrophages is often debated. Here we ask whether steady-state, lymphoid-tissue-resident conventional DCs (cDCs), plasmacytoid DCs (pDCs), and macrophages share a common macrophage-DC-restricted precursor (MDP). Using new clonal culture assays combined with adoptive transfer, we found that MDP fractions isolated by previous strategies are dominated by precursors of macrophages and monocytes, include some multipotent precursors of other hematopoietic lineages, but contain few precursors of resident cDCs and pDCs and no detectable common precursors restricted to these DC types and macrophages. Overall we find no evidence for a common restricted MDP leading to both macrophages and FL-dependent, resident cDCs and pDCs. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 76 FR 64353 - Request for Public Comment on Draft Document: “Criteria for a Recommended Standard: Occupational...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-18

    ... Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention (CDC...: The National Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control..., Director, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention...

  10. Interactions Between Macrophages of Guinea Pigs and Salmonellae III. Bactericidal Action and Cytophilic Antibodies of Macrophages of Infected Guinea Pigs

    PubMed Central

    Hsu, H. S.; Mayo, Donald R.

    1973-01-01

    The fate of virulent Salmonella typhimurium within macrophages of guinea pigs was assessed by a suspended cell culture procedure. The present study confirmed that macrophages of normal guinea pigs were capable of inactivating the ingested salmonellae. Macrophages of previously infected guinea pigs were not endowed with any significant increase in their ability to eliminate the ingested pathogen. However, the immune macrophages were observed to clump together tightly when they were exposed to salmonellae. This phenomenon was attributed to the presence of specific cytophilic antibodies on the immune macrophages. When immune macrophages were inactivated with Merthiolate, they agglutinated with both the H and the O antigens of S. typhimurium, but not with the O antigens of other species of Salmonella nor with the O antigens of Escherichia coli. Cytophilic antibodies could be eluted from immune macrophages by incubation in the absence of immune serum. Conversely, cytophilic antibodies could be passively transferred onto normal macrophages by incubation in the presence of immune serum. Furthermore, using immune serum previously adsorbed with the O antigens of S. typhimurium, cytophilic antibodies against the H antigens alone could be transferred onto normal macrophages, or those against the O antigens alone could be eluted from immune macrophages. These data suggest that immune macrophages possess specific cytophilic antibodies against both the H and the O antigens of S. typhimurium. It is proposed that the presence of cytophilic antibodies on immune macrophages represents an expression of antibacterial cellular immunity by enhanced clumping and phagocytic activities of the macrophages. PMID:4579899

  11. Estimation of benefit of prevention of occupational cancer for comparative risk assessment: methods and examples

    PubMed Central

    Lee, Lukas Jyuhn-Hsiarn; Chang, Yu-Yin; Liou, Saou-Hsing

    2012-01-01

    Objectives To quantify the life years gained and financial savings by preventing a case of occupational cancer. Methods The authors retrieved data from the Taiwan Cancer Registry and linked them with the National Mortality Registry to estimate the survival functions for major occupational cancers: lung, pleural mesothelioma, urinary bladder and leukaemia. Assuming a constant excess hazard for each type of cancer, the authors extrapolated lifetime survival functions by the Monte Carlo method. For each patient with cancer, the authors simulated an age- and gender-matched person without cancer based on vital statistics of Taiwan to estimate life expectancy and expected years of life lost (EYLL). By using the reimbursement data from the National Health Insurance Research Database, the authors calculated the average monthly healthcare expenditures, which were summed to estimate the lifetime healthcare expenditures after adjusting for the corresponding monthly survival probability. Results A total of 51 408, 136, 12 891 and 5285 new cases of lung, pleural mesothelioma, bladder and leukaemia cancers, respectively, were identified during 1997–2005 and followed until the end of 2007. The EYLL was predicted to be 13.7±0.1, 18.9±0.7, 4.7±0.3 and 19.4±0.5 years for these cancers, respectively, and the lifetime healthcare expenditures with a 3% annual discount were predicted to be US$22 359, US$14 900, US$51 987 and US$59 741, respectively. Conclusions The burden of these occupational cancers, in terms of EYLL and lifetime healthcare expenditures, was substantial. Such estimates may provide useful empirical evidence for comparative risk assessment that can be applied in health policy-making and clinical decision-making. PMID:22576592

  12. Isoliquiritigenin, a flavonoid from licorice, blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE{sub 2} and IL-6

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Haixia; Zhang, Xinhua; Chen, Xuewei

    M2 macrophage polarization is implicated in colorectal cancer development. Isoliquiritigenin (ISL), a flavonoid from licorice, has been reported to prevent azoxymethane (AOM) induced colon carcinogenesis in animal models. Here, in a mouse model of colitis-associated tumorigenesis induced by AOM/dextran sodium sulfate (DSS), we investigated the chemopreventive effects of ISL and its mechanisms of action. Mice were treated with AOM/DSS and randomized to receive either vehicle or ISL (3, 15 and 75 mg/kg). Tumor load, histology, immunohistochemistry, and gene and protein expressions were determined. Intragastric administration of ISL for 12 weeks significantly decreased colon cancer incidence, multiplicity and tumor size bymore » 60%, 55.4% and 42.6%, respectively. Moreover, ISL inhibited M2 macrophage polarization. Such changes were accompanied by downregulation of PGE{sub 2} and IL-6 signaling. Importantly, depletion of macrophages by clodronate (Clod) or zoledronic acid (ZA) reversed the effects of ISL. In parallel, in vitro studies also demonstrated that ISL limited the M2 polarization of RAW264.7 cells and mouse peritoneal macrophages with concomitant inactivation of PGE{sub 2}/PPARδ and IL-6/STAT3 signaling. Conversely, exogenous addition of PGE{sub 2} or IL-6, or overexpression of constitutively active STAT3 reversed ISL-mediated inhibition of M2 macrophage polarization. In summary, dietary flavonoid ISL effectively inhibits colitis-associated tumorigenesis through hampering M2 macrophage polarization mediated by the interplay between PGE{sub 2} and IL-6. Thus, inhibition of M2 macrophage polarization is likely to represent a promising strategy for chemoprevention of colorectal cancer. - Highlights: • Isoliquiritigenin (ISL) prevents colitis-associated tumorigenesis. • ISL inhibits M2 macrophage polarization in vivo and in vitro. • ISL inhibits PGE{sub 2} and IL-6 signaling in colitis-associated tumorigenesis. • ISL may be an attractive candidate

  13. Occupational Respiratory Cancer in Korea

    PubMed Central

    Kim, Hyoung Ryoul

    2010-01-01

    Malignant mesothelioma and lung cancer are representative examples of occupational cancer. Lung cancer is the leading cause of cancer death, and the incidence of malignant mesothelioma is expected to increase sharply in the near future. Although information about lung carcinogen exposure is limited, it is estimated that the number of workers exposed to carcinogens has declined. The first official case of occupational cancer was malignant mesothelioma caused by asbestos exposure in the asbestos textile industry in 1992. Since then, compensation for occupational respiratory cancer has increased. The majority of compensated lung cancer was due to underlying pneumoconiosis. Other main causative agents of occupational lung cancer included asbestos, hexavalent chromium, and crystalline silica. Related jobs included welders, foundry workers, platers, plumbers, and vehicle maintenance workers. Compensated malignant mesotheliomas were associated with asbestos exposure. Epidemiologic studies conducted in Korea have indicated an elevated risk of lung cancer in pneumoconiosis patients, foundry workers, and asbestos textile workers. Occupational respiratory cancer has increased during the last 10 to 20 yr though carcinogen-exposed population has declined in the same period. More efforts to advance the systems for the investigation, prevention and management of occupational respiratory cancer are needed. PMID:21258597

  14. Conditioned medium from persistently RSV-infected macrophages alters transcriptional profile and inflammatory response of non-infected macrophages.

    PubMed

    Rivera-Toledo, Evelyn; Salido-Guadarrama, Iván; Rodríguez-Dorantes, Mauricio; Torres-González, Laura; Santiago-Olivares, Carlos; Gómez, Beatriz

    2017-02-15

    Cells susceptible to persistent viral infections undergo important changes in their biological functions as a consequence of the expression of viral gene products that are capable of altering the gene expression profile of the host cell. Previously, we reported that persistence of the RSV genome in a mouse macrophage cell line induces important alterations in cell homeostasis, including constitutive expression of IFN-β and other pro-inflammatory cytokines. Here, we postulated that changes in the homeostasis of non-infected macrophages could be induced by soluble factors secreted by persistently RSV- infected macrophages. To test this hypothesis, non-infected mouse macrophages were treated with conditioned medium (CM) collected from cultures of persistently RSV-infected macrophages. Total RNA was extracted and a microarray-based gene expression analysis was performed. Non-infected macrophages, treated under similar conditions with CM obtained from cultures of non-infected macrophages, were used as a control to establish differential gene expression between the two conditions. Results showed that CM from the persistently RSV-infected cultures altered expression of a total of 95 genes in non-infected macrophages, resulting in an antiviral gene-transcription profile along with inhibition of the inflammatory response, since some inflammatory genes were down-regulated, including Nlrp3 and Il-1 β, both related to the inflammasome pathway. However, down-regulation of Nlrp3 and Il-1 β was reversible upon acute RSV infection. Additionally, we observed that the inflammatory response, evaluated by secreted IL-1 β, a final product of the inflammasome activity, was enhanced during acute RSV infection in macrophages treated with CM from persistently RSV-infected cultures, compared to that in macrophages treated with the control CM. This suggests that soluble factors secreted during RSV persistence may induce an exacerbated inflammatory response in non-infected cells

  15. Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

    PubMed

    Bai, Xiyuan; Stitzel, Jerry A; Bai, An; Zambrano, Cristian A; Phillips, Matthew; Marrack, Philippa; Chan, Edward D

    2017-09-01

    Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB), but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we used a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR)-mecamylamine-as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR. We also determined whether nicotine impaired macrophage autophagy and whether nicotine-exposed T regulatory cells (Tregs) could subvert macrophage anti-MTB immunity. Mecamylamine reduced the CS extract increase in MTB burden by 43%. CS extract increase in MTB was also significantly attenuated in macrophages from mice with genetic disruption of either the α7, β2, or β4 subunit of nAChR. Nicotine inhibited autophagosome formation in MTB-infected THP-1 cells and primary murine alveolar macrophages, as well as increased the intracellular MTB burden. Nicotine increased migration of THP-1 cells, consistent with the increased number of macrophages found in the lungs of smokers. Nicotine induced Tregs to produce transforming growth factor-β. Naive mouse macrophages co-cultured with nicotine-exposed Tregs had significantly greater numbers of viable MTB recovered with increased IL-10 production and urea production, but no difference in secreted nitric oxide as compared with macrophages cocultured with unexposed Tregs. We conclude that nicotine in CS plays an important role in subverting macrophage control of MTB infection.

  16. 29 CFR 1910.39 - Fire prevention plans.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 5 2012-07-01 2012-07-01 false Fire prevention plans. 1910.39 Section 1910.39 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Exit Routes and Emergency Planning § 1910.39 Fire prevention plans. (a...

  17. [Work-related musculoskeletal disorders and their association with occupational nursing].

    PubMed

    Barboza, Michele Cristiene Nachtigall; Milbrath, Viviane Marten; Bielemann, Valquíria Machado; de Siqueira, Hedi Crecencia Heckler

    2008-12-01

    Work-related musculoskeletal diseases (MSD) are disorders in the musculoskeletal structures caused by chronic occupational processes. The objective of this study was to get to know scientific papers on MSD related to the nursing profession. A bibliographic research of the last ten years was conducted at Health Virtual Library using the main data bases. Twenty-one summaries were found. Among them, thirteen were selected because they specifically focused on the subject. Three main areas were identified: occupational health nurses in relation to MSDs--their importance in health prevention and promotion; Ergonomics as MSDs prevention method: performed as changes on work consider risk factors; Vulnerability of Nursing staff to MSDs--predisposing factors to disease caused by inappropriate working conditions. The conclusion was that an occupational and ergonomic health service is important to prevent MSDs, especially among the nursing staff.

  18. Macrophage heterogeneity in liver injury and fibrosis.

    PubMed

    Tacke, Frank; Zimmermann, Henning W

    2014-05-01

    Hepatic macrophages are central in the pathogenesis of chronic liver injury and have been proposed as potential targets in combatting fibrosis. Recent experimental studies in animal models revealed that hepatic macrophages are a remarkably heterogeneous population of immune cells that fulfill diverse functions in homeostasis, disease progression, and regression from injury. These range from clearance of pathogens or cellular debris and maintenance of immunological tolerance in steady state conditions; central roles in initiating and perpetuating inflammation in response to injury; promoting liver fibrosis via activating hepatic stellate cells in chronic liver damage; and, finally, resolution of inflammation and fibrosis by degradation of extracellular matrix and release of anti-inflammatory cytokines. Cellular heterogeneity in the liver is partly explained by the origin of macrophages. Hepatic macrophages can either arise from circulating monocytes, which are recruited to the injured liver via chemokine signals, or from self-renewing embryo-derived local macrophages, termed Kupffer cells. Kupffer cells appear essential for sensing tissue injury and initiating inflammatory responses, while infiltrating Ly-6C(+) monocyte-derived macrophages are linked to chronic inflammation and fibrogenesis. In addition, proliferation of local or recruited macrophages may possibly further contribute to their accumulation in injured liver. During fibrosis regression, monocyte-derived cells differentiate into Ly-6C (Ly6C, Gr1) low expressing 'restorative' macrophages and promote resolution from injury. Understanding the mechanisms that regulate hepatic macrophage heterogeneity, either by monocyte subset recruitment, by promoting restorative macrophage polarization or by impacting distinctive macrophage effector functions, may help to develop novel macrophage subset-targeted therapies for liver injury and fibrosis. Copyright © 2014 European Association for the Study of the Liver

  19. Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice.

    PubMed

    Bijnen, Mitchell; Josefs, Tatjana; Cuijpers, Ilona; Maalsen, Constantijn J; van de Gaar, José; Vroomen, Maria; Wijnands, Erwin; Rensen, Sander S; Greve, Jan Willem M; Hofker, Marten H; Biessen, Erik A L; Stehouwer, Coen D A; Schalkwijk, Casper G; Wouters, Kristiaan

    2017-10-26

    Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c + proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development. vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr -/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH. Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c + and CD11c - macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c + ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes. ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise

  20. Lymph Node Macrophages Restrict Murine Cytomegalovirus Dissemination

    PubMed Central

    Farrell, Helen E.; Davis-Poynter, Nick; Bruce, Kimberley; Lawler, Clara; Dolken, Lars; Mach, Michael

    2015-01-01

    ABSTRACT Cytomegaloviruses (CMVs) establish chronic infections that spread from a primary entry site to secondary vascular sites, such as the spleen, and then to tertiary shedding sites, such as the salivary glands. Human CMV (HCMV) is difficult to analyze, because its spread precedes clinical presentation. Murine CMV (MCMV) offers a tractable model. It is hypothesized to spread from peripheral sites via vascular endothelial cells and associated monocytes. However, viral luciferase imaging showed footpad-inoculated MCMV first reaching the popliteal lymph nodes (PLN). PLN colonization was rapid and further spread was slow, implying that LN infection can be a significant bottleneck. Most acutely infected PLN cells were CD169+ subcapsular sinus macrophages (SSM). Replication-deficient MCMV also reached them, indicating direct infection. Many SSM expressed viral reporter genes, but few expressed lytic genes. SSM expressed CD11c, and MCMV with a cre-sensitive fluorochrome switch showed switched infected cells in PLN of CD11c-cre mice but yielded little switched virus. SSM depletion with liposomal clodronate or via a CD169-diphtheria toxin receptor transgene shifted infection to ER-TR7+ stromal cells, increased virus production, and accelerated its spread to the spleen. Therefore, MCMV disseminated via LN, and SSM slowed this spread by shielding permissive fibroblasts and poorly supporting viral lytic replication. IMPORTANCE HCMV chronically infects most people, and it can cause congenital disability and harm the immunocompromised. A major goal of vaccination is to prevent systemic infection. How this is established is unclear. Restriction to humans makes HCMV difficult to analyze. We show that peripheral MCMV infection spreads via lymph nodes. Here, MCMV infected filtering macrophages, which supported virus replication poorly. When these macrophages were depleted, MCMV infected susceptible fibroblasts and spread faster. The capacity of filtering macrophages to limit

  1. Maternal occupational exposure to polycyclic aromatic hydrocarbons and congenital heart defects among offspring in the national birth defects prevention study.

    PubMed

    Lupo, Philip J; Symanski, Elaine; Langlois, Peter H; Lawson, Christina C; Malik, Sadia; Gilboa, Suzanne M; Lee, Laura J; Agopian, A J; Desrosiers, Tania A; Waters, Martha A; Romitti, Paul A; Correa, Adolfo; Shaw, Gary M; Mitchell, Laura E

    2012-11-01

    There is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) results in congenital heart defects (CHDs); however, to our knowledge, this relationship has not been examined in humans. Therefore, we conducted a case-control study assessing the association between estimated maternal occupational exposure to PAHs and CHDs in offspring. Data on CHD cases and control infants were obtained from the National Birth Defects Prevention Study for the period of 1997 to 2002. Exposure to PAHs was assigned by industrial hygienist consensus, based on self-reported maternal occupational histories from 1 month before conception through the third month of pregnancy. Logistic regression was used to evaluate the association between maternal occupational PAH exposure and specific CHD phenotypic subtypes among offspring. The prevalence of occupational PAH exposure was 4.0% in CHD case mothers (76/1907) and 3.6% in control mothers (104/2853). After adjusting for maternal age, race or ethnicity, education, smoking, folic acid supplementation, and study center, exposure was not associated with conotruncal defects (adjusted odds ratio [AOR], 0.98; 95% confidence interval [CI], 0.58-1.67), septal defects (AOR, 1.28; 95% CI, 0.86-1.90), or with any isolated CHD subtype. Our findings do not support an association between potential maternal occupational exposure to PAHs and various CHDs in a large, population-based study. For CHD phenotypic subtypes in which modest nonsignificant associations were observed, future investigations could be improved by studying populations with a higher prevalence of PAH exposure and by incorporating information on maternal and fetal genotypes related to PAH metabolism. Birth Defects Research (Part A), 2012. Copyright © 2012 Wiley Periodicals, Inc.

  2. The PD-1/PD-L1 axis may be aberrantly activated in occupational cholangiocarcinoma.

    PubMed

    Sato, Yasunori; Kinoshita, Masahiko; Takemura, Shigekazu; Tanaka, Shogo; Hamano, Genya; Nakamori, Shoji; Fujikawa, Masahiro; Sugawara, Yasuhiko; Yamamoto, Takatsugu; Arimoto, Akira; Yamamura, Minako; Sasaki, Motoko; Harada, Kenichi; Nakanuma, Yasuni; Kubo, Shoji

    2017-03-01

    An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  3. [OCCUPATIONAL HEALTH RISK ASSESSMENT AND MANAGEMENT IN WORKERS IN IMPROVEMENT OF NATIONAL POLICY IN OCCUPATIONAL HYGIENE AND SAFETY].

    PubMed

    Shur, P Z; Zaĭtseva, N V; Alekseev, V B; Shliapnikov, D M

    2015-01-01

    In accordance with the international documents in the field of occupational safety and hygiene, the assessment and minimization of occupational risks is a key instrument for the health maintenance of workers. One of the main ways to achieve it is the minimization of occupational risks. Correspondingly, the instrument for the implementation of this method is the methodology of analysis of occupational risks. In Russian Federation there were the preconditions for the formation of the system for the assessment and management of occupational risks. As the target of the national (state) policy in the field of occupational safety in accordance with ILO Conventions it can be offered the prevention of accidents and injuries to health arising from work or related with it, minimizing the causes of hazards inherent in the working environment, as far as it is reasonably and practically feasible. Global trend ofusing the methodology of the assessment and management of occupational risks to life and health of citizens requires the improvement of national policies in the field of occupational hygiene and safety. Achieving an acceptable level of occupational risk in the formation of national policy in the field of occupational hygiene and safety can be considered as one of the main tasks.

  4. The ineffectiveness of coumarin treatment on thermal oedema of macrophage-free rats.

    PubMed Central

    Piller, N. B.

    1976-01-01

    The administration of silica prevents coumarin-stimulated lysis of accumulated abnormal protein. This impairs the resolution of thermal oedema which is normally increased with coumarin administration. Evidence suggests that there is a rapid differentiation and infiltration of monocytes into the tissues and that these are selectively retained. This is aided by coumarin which increases tissue permeability. Coumarin also injures the vascular endothelium of some vessels, allowing extra protein and fluid into the tissues. Death of recently differentiated macrophages and subsequent release of their lysosomal contents into the extra-cellular spaces may be responsible for the changes in serum enzyme levels. It would seem that macrophages are the only cells in which coumarin stimulates increased phagocytosis, enzyme production and proteolysis. PMID:178336

  5. Acute Penicillium marneffei infection stimulates host M1/M2a macrophages polarization in BALB/C mice.

    PubMed

    Dai, Xiaoying; Mao, Congzheng; Lan, Xiuwan; Chen, Huan; Li, Meihua; Bai, Jing; Deng, Jingmin; Liang, Qiuli; Zhang, Jianquan; Zhong, Xiaoning; Liang, Yi; Fan, Jiangtao; Luo, Honglin; He, Zhiyi

    2017-08-18

    Penicillium marneffei (P. marneffei) is a thermally dimorphic fungus pathogen that causes fatal infection. Alveolar macrophages are innate immune cells that have critical roles in protection against pulmonary fungal pathogens and the macrophage polarization state has the potential to be a deciding factor in disease progression or resolution. The aim of this study was to investigate mouse alveolar macrophage polarization states during P. marneffei infection. We used enzyme-linked immunosorbent (ELISA) assays, quantitative real-time PCR (qRT-PCR), and Griess, arginase activity to evaluate the phenotypic markers of alveolar macrophages from BALB/C mice infected with P. marneffei. We then treated alveolar macrophages from infected mice with P. marneffei cytoplasmic yeast antigen (CYA) and investigated alveolar macrophage phenotypic markers in order to identify macrophage polarization in response to P. marneffei antigens. Our results showed: i) P. marneffei infection significantly enhanced the expression of classically activated macrophage (M1)-phenotypic markers (inducible nitric oxide synthase [iNOS] mRNA, nitric oxide [NO], interleukin-12 [IL-12], tumor necrosis factor-alpha [TNF-α]) and alternatively activated macrophage (M2a)-phenotypic markers (arginase1 [Arg1] mRNA, urea) during the second week post-infection. This significantly decreased during the fourth week post-infection. ii) During P. marneffei infection, CYA stimulation also significantly enhanced the expression of M1 and M2a-phenotypic markers, consistent with the results for P. marneffei infection and CYA stimulation preferentially induced M1 subtype. The data from the current study demonstrated that alveolar macrophage M1/M2a subtypes were present in host defense against acute P. marneffei infection and that CYA could mimic P. marneffei to induce a host immune response with enhanced M1 subtype. This could be useful for investigating the enhancement of host anti-P. marneffei immune responses and to

  6. Macrophages in tissue repair, regeneration, and fibrosis

    PubMed Central

    Wynn, Thomas A.; Vannella, Kevin M.

    2016-01-01

    Inflammatory monocytes and resident tissue macrophages are key regulators of tissue repair, regeneration, and fibrosis. Following tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, with uncontrolled inflammatory mediator and growth factor production, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contributing to a state of persistent injury, which may lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue regenerating phenotypes following injury, and highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically. PMID:26982353

  7. Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters

    DTIC Science & Technology

    2016-05-20

    ANDV strain Chile -9717869 (27) was propagated in Vero E6 cells 122 (Vero C1008, ATCC CRL 1586). Preparation of twice-plaque-purified ANDV stock has...Research and Material Command, Military 537 Infectious Disease Research Program , Program Area T. Research reported in this publication 538 was also...prior to kidney, involvement, and diagnosed by viral 684 inclusions in lung macrophages. European journal of clinical microbiology & infectious

  8. [Welfare State and public health: the role of occupational health].

    PubMed

    Benavides, Fernando G; Delclós, Jordi; Serra, Consol

    2017-09-21

    In the context of the current crisis of the Welfare State, occupational health can contribute significantly to its sustainability by facilitating decent and healthy employment throughout the working life. To this end, occupational health must take on the challenge of promoting health, preventing and managing injuries, illnesses and disability, based on better coordination of prevention services, mutual insurance companies, and health services, as well as by empowering the leadership in prevention of companies and the active participation of those who work. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Dusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner

    PubMed Central

    Vandereyken, Maud; Jacques, Sophie; Van Overmeire, Eva; Amand, Mathieu; Rocks, Natacha; Delierneux, Céline; Singh, Pratibha; Singh, Maneesh; Ghuysen, Camille; Wathieu, Caroline; Zurashvili, Tinatin; Sounni, Nor Eddine; Moutschen, Michel; Gilles, Christine; Oury, Cécile; Cataldo, Didier; Van Ginderachter, Jo A.

    2017-01-01

    Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion prevents neo-angiogenesis and b-FGF-induced microvessel outgrowth. Considering the importance of angiogenesis in metastasis formation, our study aimed to investigate the role of DUSP3 in tumour cell dissemination. Using a Lewis Lung carcinoma (LLC) experimental metastasis model, we observed that DUSP3-/- mice developed larger lung metastases than littermate controls. DUSP3-/- bone marrow transfer to lethally irradiated DUSP3+/+ mice was sufficient to transfer the phenotype to DUSP3+/+ mice, indicating that hematopoietic cells compartment was involved in the increased tumour cell dissemination to lung tissues. Interestingly, we found a higher percentage of tumour-promoting Ly6Cint macrophages in DUSP3-/- LLC-bearing lung homogenates that was at least partially due to a better recruitment of these cells. This was confirmed by 1) the presence of higher number of the Ly6Bhi macrophages in DUSP3-/- lung homogenates and by 2) the better migration of DUSP3-/- bone marrow sorted monocytes, peritoneal macrophages and bone marrow derived macrophages (BMDMs), compared to DUSP3+/+ monocytes, macrophages and BMDMs, in response to LLC-conditioned medium. Our study demonstrates that DUSP3 phosphatase plays a key role in metastatic growth through a mechanism involving the recruitment of macrophages towards LLC-bearing lungs. PMID:29020102

  10. Teaching Occupational Health to Physicians

    ERIC Educational Resources Information Center

    Wegman, David H.; And Others

    1978-01-01

    A comprehensive training program is described that prepares students to identify and prevent occupational disease, emphasizing public health. Content areas include epidemiology and biostatistics, toxicology, industrial hygiene, safety and ergonomics, policy issues, administration, and clinical aspects. (Author/LBH)

  11. Histone deacetylase 7 promotes Toll-like receptor 4-dependent proinflammatory gene expression in macrophages.

    PubMed

    Shakespear, Melanie R; Hohenhaus, Daniel M; Kelly, Greg M; Kamal, Nabilah A; Gupta, Praveer; Labzin, Larisa I; Schroder, Kate; Garceau, Valerie; Barbero, Sheila; Iyer, Abishek; Hume, David A; Reid, Robert C; Irvine, Katharine M; Fairlie, David P; Sweet, Matthew J

    2013-08-30

    Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target.

  12. Histone Deacetylase 7 Promotes Toll-like Receptor 4-dependent Proinflammatory Gene Expression in Macrophages*

    PubMed Central

    Shakespear, Melanie R.; Hohenhaus, Daniel M.; Kelly, Greg M.; Kamal, Nabilah A.; Gupta, Praveer; Labzin, Larisa I.; Schroder, Kate; Garceau, Valerie; Barbero, Sheila; Iyer, Abishek; Hume, David A.; Reid, Robert C.; Irvine, Katharine M.; Fairlie, David P.; Sweet, Matthew J.

    2013-01-01

    Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target. PMID:23853092

  13. EAACI position paper on occupational rhinitis

    PubMed Central

    Moscato, Gianna; Vandenplas, Olivier; Van Wijk, Roy Gerth; Malo, Jean-Luc; Perfetti, Luca; Quirce, Santiago; Walusiak, Jolanta; Castano, Roberto; Pala, Gianni; Gautrin, Denyse; De Groot, Hans; Folletti, Ilenia; Yacoub, Mona Rita; Siracusa, Andrea

    2009-01-01

    The present document is the result of a consensus reached by a panel of experts from European and non-European countries on Occupational Rhinitis (OR), a disease of emerging relevance which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored on that of occupational asthma, as well as a diagnostic algorithm based on steps allowing for different levels of diagnostic evidence are proposed. The needs for future research are pointed out. Key messages are issued for each item. PMID:19257881

  14. Augmented macrophage differentiation and polarization of tumor-associated macrophages towards M1 subtype in listeria-administered tumor-bearing host.

    PubMed

    Rai, Rakesh K; Vishvakarma, Naveen K; Mohapatra, Tribhuban M; Singh, Sukh Mahendra

    2012-09-01

    This study investigates the effect of Listeria administration on differentiation of macrophages from precursor bone marrow cells and functional status of tumor-associated macrophages (TAM). Listeria administration not only resulted in an augmented infiltration of tumor by F4/80 macrophages but also repolarized the functional status of TAM displaying features of some M1 macrophage subtype with upregulated phagocytosis and tumoricidal activity accompanied by altered expression of monocarboxylate transporter-1, toll-like receptor-2, surface markers: CD11c, interleukin-2 receptor, CD62L, and secreted molecules: nitric oxide, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor. Declined tumor cell survival and modulated repertoire of cytokines: interferon-γ, IL-6, IL-10, and transforming growth factor-β in tumor microenvironment indicated their role in polarization of TAM towards proinflammatory state. Bone marrow cell of Listeria-administered tumor-bearing mice showed augmented survival, declined expression of p53 upregulated modulator of apoptosis with an upregulated differentiation into activation responsive bone marrow-derived macrophages along with altered expression of macrophage-colony stimulating factor, macrophage-colony stimulating factor receptor, and granulocyte macrophage-colony stimulating factor receptor. These findings indicate that Listeria infection is associated with an augmented differentiation of macrophages accompanied by tumoricidal activation of TAM.

  15. Colonic macrophage polarization in homeostasis, inflammation, and cancer

    PubMed Central

    Appleyard, Caroline B.

    2016-01-01

    Our review focuses on the colonic macrophage, a monocyte-derived, tissue-resident macrophage, and the role it plays in health and disease, specifically in inflammatory conditions such as inflammatory bowel disease and cancer of the colon and rectum. We give special emphasis to macrophage polarization, or phenotype, in these different states. We focus on macrophages because they are one of the most numerous leukocytes in the colon, and because they normally contribute to homeostasis through an anti-inflammatory phenotype. However, in conditions such as inflammatory bowel disease, proinflammatory macrophages are increased in the colon and have been linked to disease severity and progression. In colorectal cancer, tumor cells may employ anti-inflammatory macrophages to promote tumor growth and dissemination, whereas proinflammatory macrophages may antagonize tumor growth. Given the key roles that this cell type plays in homeostasis, inflammation, and cancer, the colonic macrophage is an intriguing therapeutic target. As such, potential macrophage-targeting strategies are discussed. PMID:27229123

  16. Isolation and Phenotyping of Intestinal Macrophages.

    PubMed

    Petit, Vanessa

    2018-01-01

    Macrophages are one of the most abundant leucocytes in the intestinal mucosa where they are essential for maintaining homeostasis. However they are also implicated in the pathogenesis of disorders such as inflammatory bowel disease (IBD), offering potential targets for novel therapies.Tissue macrophages are a heterogeneous population of immune cells that fulfill tissue-specific and niche-specific functions. These unique phenotypes likely reflect the heterogeneity of tissue macrophage origins and influence the tissue environment in which they reside. Here we describe how we can characterize and isolate the colonic macrophages.

  17. Macrophages and the Viral Dissemination Super Highway

    PubMed Central

    Klepper, Arielle; Branch, Andrea D

    2016-01-01

    Monocytes and macrophages are key components of the innate immune system yet they are often the victims of attack by infectious agents. This review examines the significance of viral infection of macrophages. The central hypothesis is that macrophage tropism enhances viral dissemination and persistence, but these changes may come at the cost of reduced replication in cells other than macrophages. PMID:26949751

  18. Overexpression of IL-10 in C2D macrophages promotes a macrophage phenotypic switch in adipose tissue environments.

    PubMed

    Xie, Linglin; Fu, Qiang; Ortega, Teresa M; Zhou, Lun; Rasmussen, Dane; O'Keefe, Jacy; Zhang, Ke K; Chapes, Stephen K

    2014-01-01

    Adipose tissue macrophages are a heterogeneous collection of classically activated (M1) and alternatively activated (M2) macrophages. Interleukin 10 (IL-10) is an anti-inflammatory cytokine, secreted by a variety of cell types including M2 macrophages. We generated a macrophage cell line stably overexpressing IL-10 (C2D-IL10) and analyzed the C2D-IL10 cells for several macrophage markers after exposure to adipocytes compared to C2D cells transfected with an empty vector (C2D-vector). C2D-IL10 macrophage cells expressed more CD206 when co-cultured with adipocytes than C2D-vector cells; while the co-cultured cell mixture also expressed higher levels of Il4, Il10, Il1β and Tnf. Since regular C2D cells traffic to adipose tissue after adoptive transfer, we explored the impact of constitutive IL-10 expression on C2D-IL10 macrophages in adipose tissue in vivo. Adipose tissue-isolated C2D-IL10 cells increased the percentage of CD206(+), CD301(+), CD11c(-)CD206(+) (M2) and CD11c(+)CD206(+) (M1b) on their cell surface, compared to isolated C2D-vector cells. These data suggest that the expression of IL-10 remains stable, alters the C2D-IL10 macrophage cell surface phenotype and may play a role in regulating macrophage interactions with the adipose tissue.

  19. Burkholderia cenocepacia Induces Macropinocytosis to Enter Macrophages.

    PubMed

    Rosales-Reyes, Roberto; Sánchez-Gómez, Concepción; Ortiz-Navarrete, Vianney; Santos-Preciado, José Ignacio

    2018-01-01

    Burkholderia cenocepacia is an opportunistic pathogen that infects individuals with cystic fibrosis, chronic granulomatous disease, and other immunocompromised states. B. cenocepacia survives in macrophages in membrane-bound vacuoles; however, the mechanism by which B. cenocepacia gains entry into macrophages remains unknown. After macrophage internalization, survival of B. cenocepacia within a bacteria-containing membrane vacuole (BcCV) is associated with its ability to arrest the maturation of the BcCV. In this study, we show that B. cenocepacia induces localized membrane ruffling, macropinocytosis, and macropinosomes-like compartments upon contact with the macrophage. The Type 3 Secretion System (T3SS) of B. cenocepacia contributes to macrophage entry and macropinosome-like compartment formation. These data demonstrate the ability of Burkholderia to enter macrophages through the induction of macropinocytosis.

  20. Immunostimulatory effect of spinach aqueous extract on mouse macrophage-like J774.1 cells and mouse primary peritoneal macrophages.

    PubMed

    Ishida, Momoko; Ose, Saya; Nishi, Kosuke; Sugahara, Takuya

    2016-07-01

    We herein report the immunostimulatory effect of spinach aqueous extract (SAE) on mouse macrophage-like J774.1 cells and mouse primary peritoneal macrophages. SAE significantly enhanced the production of interleukin (IL)-6 and tumor necrosis factor-α by both J774.1 cells and peritoneal macrophages by enhancing the expression levels of these cytokine genes. In addition, the phagocytosis activity of J774.1 cells was facilitated by SAE. Immunoblot analysis revealed that SAE activates mitogen-activated protein kinase and nuclear factor-κB cascades. It was found that SAE activates macrophages through not only TLR4, but also other receptors. The production of IL-6 was significantly enhanced by peritoneal macrophages from SAE-administered BALB/c mice, suggesting that SAE has a potential to stimulate macrophage activity in vivo. Taken together, these data indicate that SAE would be a beneficial functional food with immunostimulatory effects on macrophages.

  1. The role of macrophages in the regulation of erythroid colony growth in vitro.

    PubMed

    Wang, C Q; Udupa, K B; Lipschitz, D A

    1992-10-01

    Depletion of macrophages from murine marrow by the use of a monoclonal anti-macrophage antibody resulted in a significant increase in the number of erythroid burst forming units (BFU-E). This increase could be neutralized by the addition back to culture of macrophages or macrophage conditioned medium indicating that the suppression was mediated by soluble factors. To further characterize this effect, the addition to culture, either alone or in combination, of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the growth of BFU-E and the colony-forming unit granulocyte-macrophage (CFU-GM) was examined in macrophage-containing and macrophage-depleted cultures. The addition of IL-1 alpha to culture stimulated the release of both TNF alpha and GM-CSF and acted synergistically with both cytokines, resulting in a dose-dependent suppression of BFU-E and stimulation of CFU-GM growth. The increase in CFU-GM caused by the addition of IL-1 alpha was mediated by GM-CSF but not by TNF alpha as the increase was prevented by the addition of a monoclonal anti-GM-CSF antibody but not by anti-TNF alpha. When either TNF alpha or GM-CSF was neutralized by monoclonal antibodies the addition of IL-1 alpha resulted in a significant increase in BFU-E growth. The addition of GM-CSF to culture caused a dose-dependent suppression of BFU-E that was mediated by TNF alpha, as colony number was not reduced when GM-CSF and a monoclonal anti-TNF alpha antibody were simultaneously added to culture. TNF alpha-induced suppression of BFU-E only occurred in the presence of macrophages. In macrophage-depleted cultures, a dose-dependent suppression of BFU-E could be induced if subinhibitory concentrations of IL-1 alpha or GM-CSF were simultaneously added with increasing concentrations of TNF alpha. The effects of IL-1 alpha or GM-CSF and TNF alpha were markedly synergistic so that the doses required to induce

  2. Effect of lipopolysaccharide on protein accumulation by murine peritoneal macrophages: the correlation to activation for macrophage tumoricidal function

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tannenbaum, C.S.

    1987-01-01

    The protein synthetic patterns of tumoricidal murine peritoneal macrophage populations have been compared to those of non-tumoricidal populations utilizing two dimensional polyacrylamide gel electrophoresis (2D PAGE) of (/sup 35/S)-methionine-labeled proteins. While the protein synthetic patterns exhibited by resident, inflammatory and activated macrophages had numerous common features which distinguished them from the other normal non-macrophage cell types examined, unique proteins also distinguished each macrophage population from the others. Peritoneal macrophages elicited by treatment with heat killed Propionibacterium acnes, the live, attenuated Mycobacterium bovis strain BCG, Listeria monocytogenes and the protozoan flagellate Trypanosoma rhodesiense, all exhibited tumoricidal activity in 16h or 72hmore » functional assays, and shared a common protein synthetic profile which differentiated them from the synthetic patterns characteristic of the non-tumoricidal resident and inflammatory macrophages.« less

  3. [Surveillance groups and occupational phisicians for prevention and security in work environment: legal aspects].

    PubMed

    Aceto, A

    2006-01-01

    Italian jurisdiction, since the setting up of the Republic in 1948, has experienced a real and proper Copernican revolution, not only in the field of prevention of accidents and safety at work, which has meant that at the centre of the system there is no longer a State-finality but the individual person, in the form of inviolable rights that the Democratic Republic-vehicle recognises and guarantees in every place, including all places of occupation. To this end the entrepreneur/employer has become the guarantor of the health of his employees through a complex series of laws and regulations that imposes the adoption of safety measures on an individual, general and organizational level in the company. This guarantee has been reinforced by bringing in penalties for all those evasions or violations of these obligations of the entrepreneur/employer. The centralizing of the culture of prevention has meant that all the controls converge on the judicial police, with the head of the surveillance bodies having the status of officer of the judicial police, and with the adoption of regulations that follow the code of criminal procedures, which, while being binding for the same surveillance bodies is also a guarantee in respecting the right to be defended of the entrepreneur/employer.

  4. Evidence for apoptosis of murine macrophages by Actinobacillus actinomycetemcomitans infection.

    PubMed

    Kato, S; Muro, M; Akifusa, S; Hanada, N; Semba, I; Fujii, T; Kowashi, Y; Nishihara, T

    1995-10-01

    The gram-negative bacterium Actinobacillus actinomycetemcomitans is considered an important etiological agent in periodontal diseases. In this study, we show that A. actinomycetemcomitans strains are cytotoxic for the murine macrophage cell line J774.1. On the other hand, Porphyromonas gingivalis strains, other gram-negative oral species implicated in adult periodontitis, showed weak cytotoxic effects. For this to occur, A. actinomycetemcomitans had to gain entry into the macrophages, since cytotoxicity was prevented by cytochalasin D. We demonstrate that cell death induced by A. actinomycetemcomitans Y4 occurs through apoptosis, as shown by changes in nuclear morphology, an increase in the proportion of fragmented DNA, and the typical ladder pattern of DNA fragmentation indicative of apoptosis. We further sought to determine whether the cytotoxicity induced by A. actinomycetemcomitans Y4 could be modulated by the protein kinase inhibitors H7 and HA1004. Apoptotic cell death induced by A. actinomycetemcomitans Y4 was suppressed by H7 but was relatively unaffected by HA1004. These findings suggest that the signals of protein kinases may regulate apoptosis induced by A. actinomycetemcomitans Y4. The ability of A. actinomycetemcomitans to promote the apoptosis of macrophages may be important for the initiation of infection and the development of periodontal diseases.

  5. Evidence for apoptosis of murine macrophages by Actinobacillus actinomycetemcomitans infection.

    PubMed Central

    Kato, S; Muro, M; Akifusa, S; Hanada, N; Semba, I; Fujii, T; Kowashi, Y; Nishihara, T

    1995-01-01

    The gram-negative bacterium Actinobacillus actinomycetemcomitans is considered an important etiological agent in periodontal diseases. In this study, we show that A. actinomycetemcomitans strains are cytotoxic for the murine macrophage cell line J774.1. On the other hand, Porphyromonas gingivalis strains, other gram-negative oral species implicated in adult periodontitis, showed weak cytotoxic effects. For this to occur, A. actinomycetemcomitans had to gain entry into the macrophages, since cytotoxicity was prevented by cytochalasin D. We demonstrate that cell death induced by A. actinomycetemcomitans Y4 occurs through apoptosis, as shown by changes in nuclear morphology, an increase in the proportion of fragmented DNA, and the typical ladder pattern of DNA fragmentation indicative of apoptosis. We further sought to determine whether the cytotoxicity induced by A. actinomycetemcomitans Y4 could be modulated by the protein kinase inhibitors H7 and HA1004. Apoptotic cell death induced by A. actinomycetemcomitans Y4 was suppressed by H7 but was relatively unaffected by HA1004. These findings suggest that the signals of protein kinases may regulate apoptosis induced by A. actinomycetemcomitans Y4. The ability of A. actinomycetemcomitans to promote the apoptosis of macrophages may be important for the initiation of infection and the development of periodontal diseases. PMID:7558299

  6. Role of urease in megasome formation and Helicobacter pylori survival in macrophages

    PubMed Central

    Schwartz, Justin T.; Allen, Lee-Ann H.

    2007-01-01

    Previous studies have demonstrated that Helicobacter pylori (Hp) delays its entry into macrophages and persists inside megasomes, which are poorly acidified and accumulate early endosome autoantigen 1. Herein, we explored the role of Hp urease in bacterial survival in murine peritoneal macrophages and J774 cells. Plasmid-free mutagenesis was used to replace ureA and ureB with cat in Hp Strains 11637 and 11916. ureAB null Hp lacked detectable urease activity and did not express UreA or UreB as judged by immunoblotting. Deletion of ureAB had no effect on Hp binding to macrophages or the rate or extent of phagocytosis. However, intracellular survival of mutant organisms was impaired significantly. Immunofluorescence microscopy demonstrated that (in contrast to parental organisms) mutant Hp resided in single phagosomes, which were acidic and accumulated the lysosome marker lysosome-associated membrane protein-1 but not early endosome autoantigen 1. A similar phenotype was observed for spontaneous urease mutants derived from Hp Strain 60190. Treatment of macrophages with bafilomycin A1, NH4Cl, or chloroquine prevented acidification of phagosomes containing mutant Hp. However, only ammonium chloride enhanced bacterial viability significantly. Rescue of ureAB null organisms was also achieved by surface adsorption of active urease. Altogether, our data indicate a role for urease and urease-derived ammonia in megasome formation and Hp survival. PMID:16543403

  7. Celastrol nanomicelles attenuate cytokine secretion in macrophages and inhibit macrophage-induced corneal neovascularization in rats.

    PubMed

    Li, Zhanrong; Li, Jingguo; Zhu, Lei; Zhang, Ying; Zhang, Junjie; Yao, Lin; Liang, Dan; Wang, Liya

    The aim of the present study was to investigate the inhibitory effects of celastrol-loaded nanomicelles (CNMs) on activated macrophage-induced corneal neovascularization (CNV) in rats and cytokine secretion in macrophages. Using an angiogenesis assay in vitro, we detected the effects of CNMs on human umbilical vein endothelial cell (HUVEC) migration and invasion. In addition, the expression levels of cytokines secreted from hypoxia-induced macrophages were assessed through cytokine array analysis. The expression of hypoxia-inducible factors-1α (HIF-1α), nuclear factor-kappa B p65 (NF-κB p65), phospho-nuclear factor-kappa B p65 (phospho-NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-ERK1/2 was analyzed by western blotting. Activated macrophages were elicited through mineral oil lumbar injection, labeled with 1,19-dioctadecyl-3-3-39,39-tetramethylindocarbocyanine (DiI) and implanted into the corneal micro-pocket to induce CNV and to assess the antiangiogenic effect in rats. CNV was morphometrically analyzed using ImageJ software. Histopathological features were evaluated by immunofluorescence immunostaining for vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) on day 2 after surgery. In the present study, the results indicated that CNMs significantly inhibited the migration and invasion of HUVECs; remarkably attenuated the expression of VEGF, tumor necrosis factor-α, interleukin-1α, monocyte chemoattractant protein 1, cytokine-induced neutrophil chemoattractant 3, and MMP-9 protein; and downregulated ERK1/2, p38 MAPK, NF-κB activation, and HIF-1α expression in macrophages. The peritoneal cells elicited using mineral oil were highly purified macrophages, and the length and area of CNV were significantly decreased in the CNMs group compared with the control group. There was a significant reduction in the expression of VEGF and MMP-9 in

  8. Macrophage Polarization by Angiotensin II-type 1 Receptor Aggravates Renal Injury-acceleration of Atherosclerosis

    PubMed Central

    Yamamoto, Suguru; Yancey, Patricia G.; Zuo, Yiqin; Ma, Li-Jun; Kaseda, Ryohei; Fogo, Agnes B.; Ichikawa, Iekuni; Linton, MacRae F.; Fazio, Sergio; Kon, Valentina

    2011-01-01

    Background Angiotensin II (AII) is a major determinant of atherosclerosis. Although macrophages are the most abundant cells in atherosclerotic plaques and express AII type 1 receptor (AT1), the pathophysiologic role of macrophage AT1 in atherogenesis remains uncertain. We examined the contribution of macrophage AT1 to accelerated atherosclerosis in an AII-responsive setting induced by uninephrectomy (UNx). Methods and Results AT1−/− or AT1+/+ marrow from apolipoprotein E deficient (apoE−/−) mice was transplanted into recipient apoE−/− mice with subsequent UNx or sham operation: apoE−/−/AT1+/+→apoE−/− + Sham; apoE−/−/AT1+/+→apoE−/− + UNx; apoE−/−/AT1−/−→apoE−/− + Sham; apoE−/−/AT1−/−→apoE−/− + UNx. No differences in body weight, blood pressure, lipid profile, and serum creatinine were observed between the two UNx groups. ApoE−/−/AT1+/+→apoE−/− + UNx had significantly more atherosclerosis (16907 ± 21473 vs 116071 ± 8180 μm2, p<0.05). By contrast, loss of macrophage AT1 which reduced local AT1 expression, prevented any effect of UNx on atherosclerosis (77174 ± 9947 vs 75714 ± 11333 μm2, p=NS). Although UNx did not affect total macrophage content in the atheroma, lesions in apoE−/−/AT1−/−→apoE−/− + UNx had fewer classically activated macrophage phenotype (M1) and more alternatively activated phenotype (M2). Further, UNx did not affect plaque necrosis or apoptosis in apoE−/−/AT1−/−→apoE−/− whereas it significantly increased both (by 2- and 6-fold, respectively) in apoE−/−/AT1+/+→apoE−/− mice. Instead, apoE−/−/AT1−/−→apoE−/− had 5-fold-increase in macrophage-associated apoptotic bodies, indicating enhanced efferocytosis. In vitro studies confirmed blunted susceptibility to apoptosis, especially in M2 macrophages, and a more efficient phagocytic function of AT1−/− macrophages vs AT1+/+. Conclusions AT1 receptor of bone marrow

  9. Nitric oxide synthase 2 is required for conversion of pro-fibrogenic inflammatory CD133(+) progenitors into F4/80(+) macrophages in experimental autoimmune myocarditis.

    PubMed

    Blyszczuk, Przemyslaw; Berthonneche, Corrine; Behnke, Silvia; Glönkler, Marcel; Moch, Holger; Pedrazzini, Thierry; Lüscher, Thomas F; Eriksson, Urs; Kania, Gabriela

    2013-02-01

    Experimental autoimmune myocarditis (EAM) model mirrors important mechanisms of inflammatory dilated cardiomyopathy (iDCM). In EAM, inflammatory CD133(+) progenitors are a major cellular source of cardiac myofibroblasts in the post-inflammatory myocardium. We hypothesized that exogenous delivery of macrophage-colony-stimulating factor (M-CSF) can stimulate macrophage lineage differentiation of inflammatory progenitors and, therefore, prevent their naturally occurring myofibroblast fate in EAM. EAM was induced in wild-type (BALB/c) and nitric oxide synthase 2-deficient (Nos2(-/-)) mice and CD133(+) progenitors were isolated from inflamed hearts. In vitro, M-CSF converted inflammatory CD133(+) progenitors into nitric oxide-producing F4/80(+) macrophages and prevented transforming growth factor-β-mediated myofibroblast differentiation. Importantly, only a subset of heart-infiltrating CD133(+) progenitors expresses macrophage-specific antigen F4/80 in EAM. These CD133(+)/F4/80(hi) cells show impaired myofibrogenic potential compared with CD133(+)/F4/80(-) cells. M-CSF treatment of wild-type mice with EAM at the peak of disease markedly increased CD133(+)/F4/80(hi) cells in the myocardium, and CD133(+) progenitors isolated from M-CSF-treated mice failed to differentiate into myofibroblasts. In contrast, M-CSF was not effective in converting CD133(+) progenitors from inflamed hearts of Nos2(-/-) mice into macrophages, and M-CSF treatment did not result in increased CD133(+)/F4/80(hi) cell population in hearts of Nos2(-/-) mice. Accordingly, M-CSF prevented post-inflammatory fibrosis and left ventricular dysfunction in wild-type but not in Nos2(-/-) mice. Active and NOS2-dependent induction of macrophage lineage differentiation abrogates the myofibrogenic potential of heart-infiltrating CD133(+) progenitors. Modulating the in vivo differentiation fate of specific progenitors might become a novel approach for the treatment of inflammatory heart diseases.

  10. Data linkage between the National Birth Defects Prevention Study and the Occupational Information Network (O*NET) to assess workplace physical activity, sedentary behaviors, and emotional stressors during pregnancy.

    PubMed

    Lee, Laura J; Symanski, Elaine; Lupo, Philip J; Tinker, Sarah C; Razzaghi, Hilda; Pompeii, Lisa A; Hoyt, Adrienne T; Canfield, Mark A; Chan, Wenyaw

    2016-02-01

    Knowledge of the prevalence of work-related physical activities, sedentary behaviors, and emotional stressors among pregnant women is limited, and the extent to which these exposures vary by maternal characteristics remains unclear. Data on mothers of 6,817 infants without major birth defects, with estimated delivery during 1997 through 2009 who worked during pregnancy were obtained from the National Birth Defects Prevention Study. Information on multiple domains of occupational exposures was gathered by linking mother's primary job to the Occupational Information Network Version 9.0. The most frequent estimated physical activity associated with jobs during pregnancy was standing. Of 6,337 mothers, 31.0% reported jobs associated with standing for ≥75% of their time. There was significant variability in estimated occupational exposures by maternal age, race/ethnicity, and educational level. Our findings augment existing literature on occupational physical activities, sedentary behaviors, emotional stressors, and occupational health disparities during pregnancy. © 2015 Wiley Periodicals, Inc.

  11. Data Linkage Between the National Birth Defects Prevention Study and the Occupational Information Network (O*NET) to Assess Workplace Physical Activity, Sedentary Behaviors, and Emotional Stressors During Pregnancy

    PubMed Central

    Lee, Laura J.; Symanski, Elaine; Lupo, Philip J.; Tinker, Sarah C.; Razzaghi, Hilda; Pompeii, Lisa A.; Hoyt, Adrienne T.; Canfield, Mark A.; Chan, Wenyaw

    2016-01-01

    Background Knowledge of the prevalence of work-related physical activities, sedentary behaviors, and emotional stressors among pregnant women is limited, and the extent to which these exposures vary by maternal characteristics remains unclear. Methods Data on mothers of 6,817 infants without major birth defects, with estimated delivery during 1997 through 2009 who worked during pregnancy were obtained from the ‘National Birth Defects Prevention Study. Information on multiple domains of occupational exposures was gathered by linking mother’s primary job to the Occupational Information Network Version 9.0. Results The most frequent estimated physical activity associated with jobs during pregnancy was standing. Of 6,337 mothers, 31.0% reported jobs associated with standing for ≥ 75% of their time. There was significant variability in estimated occupational exposures by maternal age, race/ethnicity, and educational level. Conclusions Our findings augment existing literature on occupational physical activities, sedentary behaviors, emotional stressors, and occupational health disparities during pregnancy. PMID:26681357

  12. Seatbelt and seatback control for occupant protection in frontal automotive collisions

    NASA Astrophysics Data System (ADS)

    Mott, Michael; Sun, Zhen; Rajamani, Rajesh

    2013-10-01

    This paper investigates the potential benefits of an imminent collision prediction system for improving occupant protection in a frontal automotive crash. Knowledge of an impending unavoidable crash is assumed to be known 100 ms before the crash occurs. A three dof human occupant model is developed using a Lagrangian approach to represent occupant translation with respect to seat, torso rotation and neck rotation. The performance of traditional elastic seat belts is compared with that of an analytically calculated seat belt law in which the force values are calculated in real-time so as to just prevent collision with car interior. Simulations verify that the analytical seat belt force calculation results in less force on occupant for the same level of safety. Furthermore, results show that knowledge of a future collision can be used to pre-tension seat belts but can provide no additional benefits, if seat belts are the only means for active occupant protection. However, if seat tilt-back can be deployed using an on-off mechanism, such predictive knowledge of a future collision can provide significantly improved occupant protection in terms of preventing occupant collision with car interior.

  13. Occupational injuries in workers from different ethnicities

    PubMed Central

    Mekkodathil, Ahammed; El-Menyar, Ayman; Al-Thani, Hassan

    2016-01-01

    Objectives: Occupational injuries remain an important unresolved issue in many of the developing and developed countries. We aimed to outline the causes, characteristics, measures and impact of occupational injuries among different ethnicities. Materials and Methods: We reviewed the literatures using PUBMED, MEDLINE, Google Scholar and EMBASE search engine using words: “Occupational injuries” and “workplace” between 1984 and 2014. Results: Incidence of fatal occupational injuries decreased over time in many countries. However, it increased in the migrant, foreign born and ethnic minority workers in certain high risk industries. Disproportionate representations of those groups in different industries resulted in wide range of fatality rates. Conclusions: Overrepresentation of migrant workers, foreign born and ethnic minorities in high risk and unskilled occupations warrants effective safety training programs and enforcement of laws to assure safe workplaces. The burden of occupational injuries at the individual and community levels urges the development and implementation of effective preventive programs. PMID:27051619

  14. Nontransformed, GM-CSF-dependent macrophage lines are a unique model to study tissue macrophage functions.

    PubMed

    Fejer, György; Wegner, Mareike Dorothee; Györy, Ildiko; Cohen, Idan; Engelhard, Peggy; Voronov, Elena; Manke, Thomas; Ruzsics, Zsolt; Dölken, Lars; Prazeres da Costa, Olivia; Branzk, Nora; Huber, Michael; Prasse, Antje; Schneider, Robert; Apte, Ron N; Galanos, Chris; Freudenberg, Marina A

    2013-06-11

    Macrophages are diverse cell types in the first line of antimicrobial defense. Only a limited number of primary mouse models exist to study their function. Bone marrow-derived, macrophage-CSF-induced cells with a limited life span are the most common source. We report here a simple method yielding self-renewing, nontransformed, GM-CSF/signal transducer and activator of transcription 5-dependent macrophages (Max Planck Institute cells) from mouse fetal liver, which reflect the innate immune characteristics of alveolar macrophages. Max Planck Institute cells are exquisitely sensitive to selected microbial agents, including bacterial LPS, lipopeptide, Mycobacterium tuberculosis, cord factor, and adenovirus and mount highly proinflammatory but no anti-inflammatory IL-10 responses. They show a unique pattern of innate responses not yet observed in other mononuclear phagocytes. This includes differential LPS sensing and an unprecedented regulation of IL-1α production upon LPS exposure, which likely plays a key role in lung inflammation in vivo. In conclusion, Max Planck Institute cells offer an useful tool to study macrophage biology and for biomedical science.

  15. 77 FR 40622 - Mine Safety and Health Research Advisory Committee, National Institute for Occupational Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Mine Safety and Health Research Advisory Committee, National Institute for Occupational Safety and Health (MSHRAC, NIOSH..., oxygen supply partnership, safety culture, occupational health and safety management systems, preventing...

  16. Phagocytosis imprints heterogeneity in tissue-resident macrophages

    PubMed Central

    A-Gonzalez, Noelia; Quintana, Juan A.; Mazariegos, Marina; González de la Aleja, Arturo; Nicolás-Ávila, José A.; Crainiciuc, Georgiana; Rothlin, Carla V.; Peinado, Héctor; Castrillo, Antonio

    2017-01-01

    Tissue-resident macrophages display varying phenotypic and functional properties that are largely specified by their local environment. One of these functions, phagocytosis, mediates the natural disposal of billions of cells, but its mechanisms and consequences within living tissues are poorly defined. Using a parabiosis-based strategy, we identified and isolated macrophages from multiple tissues as they phagocytosed blood-borne cellular material. Phagocytosis was circadianally regulated and mediated by distinct repertoires of receptors, opsonins, and transcription factors in macrophages from each tissue. Although the tissue of residence defined the core signature of macrophages, phagocytosis imprinted a distinct antiinflammatory profile. Phagocytic macrophages expressed CD206, displayed blunted expression of Il1b, and supported tissue homeostasis. Thus, phagocytosis is a source of macrophage heterogeneity that acts together with tissue-derived factors to preserve homeostasis. PMID:28432199

  17. Burkholderia cenocepacia Induces Macropinocytosis to Enter Macrophages

    PubMed Central

    2018-01-01

    Burkholderia cenocepacia is an opportunistic pathogen that infects individuals with cystic fibrosis, chronic granulomatous disease, and other immunocompromised states. B. cenocepacia survives in macrophages in membrane-bound vacuoles; however, the mechanism by which B. cenocepacia gains entry into macrophages remains unknown. After macrophage internalization, survival of B. cenocepacia within a bacteria-containing membrane vacuole (BcCV) is associated with its ability to arrest the maturation of the BcCV. In this study, we show that B. cenocepacia induces localized membrane ruffling, macropinocytosis, and macropinosomes-like compartments upon contact with the macrophage. The Type 3 Secretion System (T3SS) of B. cenocepacia contributes to macrophage entry and macropinosome-like compartment formation. These data demonstrate the ability of Burkholderia to enter macrophages through the induction of macropinocytosis. PMID:29850514

  18. Redox Control of Inflammation in Macrophages

    PubMed Central

    Dehne, Nathalie; Grossmann, Nina; Jung, Michaela; Namgaladze, Dmitry; Schmid, Tobias; von Knethen, Andreas; Weigert, Andreas

    2013-01-01

    Abstract Macrophages are present throughout the human body, constitute important immune effector cells, and have variable roles in a great number of pathological, but also physiological, settings. It is apparent that macrophages need to adjust their activation profile toward a steadily changing environment that requires altering their phenotype, a process known as macrophage polarization. Formation of reactive oxygen species (ROS), derived from NADPH-oxidases, mitochondria, or NO-producing enzymes, are not necessarily toxic, but rather compose a network signaling system, known as redox regulation. Formation of redox signals in classically versus alternatively activated macrophages, their action and interaction at the level of key targets, and the resulting physiology still are insufficiently understood. We review the identity, source, and biological activities of ROS produced during macrophage activation, and discuss how they shape the key transcriptional responses evoked by hypoxia-inducible transcription factors, nuclear-erythroid 2-p45-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor-γ. We summarize the mechanisms how redox signals add to the process of macrophage polarization and reprogramming, how this is controlled by the interaction of macrophages with their environment, and addresses the outcome of the polarization process in health and disease. Future studies need to tackle the option whether we can use the knowledge of redox biology in macrophages to shape their mediator profile in pathophysiology, to accelerate healing in injured tissue, to fight the invading pathogens, or to eliminate settings of altered self in tumors. Antioxid. Redox Signal. 19, 595–637. PMID:23311665

  19. Asthma Among Employed Adults, by Industry and Occupation - 21 States, 2013.

    PubMed

    Dodd, Katelynn E; Mazurek, Jacek M

    2016-12-02

    Workers in various industries and occupations are at risk for work-related asthma* (1). Data from the 2006-2007 adult Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-back Survey (ACBS), an in-depth asthma survey conducted with respondents who report an asthma diagnosis, from 33 states indicated that up to 48% of adult current asthma might be related to work and could therefore potentially be prevented (2). Identification of the industries and occupations with increased prevalence of asthma might inform work-related asthma intervention and prevention efforts. To assess the industry-specific and occupation-specific proportions of adults with current asthma by state, CDC analyzed data from the 2013 BRFSS industry and occupation module, collected from 21 states for participants aged ≥18 years who, at the time of the survey interview, were employed or had been out of work for <12 months. Among these respondents, 7.7% had current asthma; based on the Asthma Call-back Survey results, this finding means as many as 2.7 million U.S. workers might have asthma caused by or exacerbated by workplace conditions. State-specific variations in the prevalence of current asthma by industry and occupation were observed. By state, current asthma prevalence was highest among workers in the information industry (18.0%) in Massachusetts and in health care support occupations (21.5%) in Michigan. Analysis of BRFSS industry and occupation and optional asthma modules can be used to identify industries and occupations to assess for asthma among workers, identify workplace exposures, and guide the design and evaluation of effective work-related asthma prevention and education programs (1).

  20. STATs and macrophage fusion.

    PubMed

    Miyamoto, Takeshi

    2013-07-01

    Macrophages play a pivotal role in host defense against multiple foreign materials such as bacteria, parasites and artificial devices. Some macrophage lineage cells, namely osteoclasts and foreign body giant cells (FBGCs), form multi-nuclear giant cells by the cell-cell fusion of mono-nuclear cells. Osteoclasts are bone-resorbing cells, and are formed in the presence of RANKL on the surface of bones, while FBGCs are formed in the presence of IL-4 or IL-13 on foreign materials such as artificial joints, catheters and parasites. Recently, fusiogenic mechanisms and the molecules required for the cell-cell fusion of these macrophage lineage cells were, at least in part, clarified. Dendritic cell specific transmembrane protein (DC-STAMP) and osteoclast stimulatory transmembrane protein (OC-STAMP), both of which comprise seven transmembrane domains, are required for both osteoclast and FBGC cell-cell fusion. STAT6 was demonstrated to be required for the cell-cell fusion of FBGCs but not osteoclasts. In this review, advances in macrophage cell-cell fusion are discussed.

  1. Macrophage activation by glycoprotein isolated from Dioscorea batatas

    PubMed Central

    Huong, Pham Thi Thu

    2011-01-01

    We demonstrate that glycoprotein isolated from Dioscorea batatas (GDB) activates macrophage function. Analysis of the infiltration of macrophages into peritoneal cavity showed GDB treatment significantly increased the recruitment of macrophages into the peritoneal cavity. In order to further confirm and investigate the mechanism of GDB on macrophage activation, we analyzed the effects of GDB on the cytokine expression including IL-1β, TNF-α, and IL-6 in mouse peritoneal macrophages. GDB increased the expression of IL-1β, TNF-α, and IL-6. Cytokine induction by GDB was further confirmed by RT-PCR and ELISA in mouse macrophage cell line, RAW264.7 cells. Treatment of RAW264.7 cells with GDB produced strong induction of NF-κB DNA binding and MAPK phosphorylation, markers for macrophage activation and important factors for cytokine gene expression. Collectively, this series of experiments indicates that GDB stimulates macrophage activation. PMID:24278568

  2. Apoptosis inhibitor of macrophage depletion decreased M1 macrophage accumulation and the incidence of cardiac rupture after myocardial infarction in mice.

    PubMed

    Ishikawa, Shohei; Noma, Takahisa; Fu, Hai Ying; Matsuzaki, Takashi; Ishizawa, Makoto; Ishikawa, Kaori; Murakami, Kazushi; Nishimoto, Naoki; Nishiyama, Akira; Minamino, Tetsuo

    2017-01-01

    Cardiac rupture is an important cause of death in the acute phase after myocardial infarction (MI). Macrophages play a pivotal role in cardiac remodeling after MI. Apoptosis inhibitor of macrophage (AIM) is secreted specifically by macrophages and contributes to macrophage accumulation in inflamed tissue by maintaining survival and recruiting macrophages. In this study, we evaluated the role of AIM in macrophage accumulation in the infarcted myocardium and cardiac rupture after MI. Wild-type (WT) and AIM‒/‒ mice underwent permanent left coronary artery ligation and were followed-up for 7 days. Macrophage accumulation and phenotypes (M1 pro-inflammatory macrophage or M2 anti-inflammatory macrophage) were evaluated by immunohistological analysis and RT-PCR. Matrix metalloproteinase (MMP) activity levels were measured by gelatin zymography. The survival rate was significantly higher (81.1% vs. 48.2%, P<0.05), and the cardiac rupture rate was significantly lower in AIM‒/‒ mice than in WT mice (10.8% vs. 31.5%, P<0.05). The number of M1 macrophages and the expression levels of M1 markers (iNOS and IL-6) in the infarcted myocardium were significantly lower in AIM‒/‒ mice than in WT mice. In contrast, there was no difference in the number of M2 macrophages and the expression of M2 markers (Arg-1, CD206 and TGF-β1) between the two groups. The ratio of apoptotic macrophages in the total macrophages was significantly higher in AIM‒/‒ mice than in WT mice, although MCP-1 expression did not differ between the two groups. MMP-2 and 9 activity levels in the infarcted myocardium were significantly lower in AIM‒/‒ mice than in WT mice. These findings suggest that AIM depletion decreases the levels of M1 macrophages, which are a potent source of MMP-2 and 9, in the infarcted myocardium in the acute phase after MI by promoting macrophage apoptosis, and leads to a decrease in the incidence of cardiac rupture and improvements in survival rates.

  3. Apoptosis inhibitor of macrophage depletion decreased M1 macrophage accumulation and the incidence of cardiac rupture after myocardial infarction in mice

    PubMed Central

    Noma, Takahisa; Fu, Hai Ying; Matsuzaki, Takashi; Ishizawa, Makoto; Ishikawa, Kaori; Murakami, Kazushi; Nishimoto, Naoki; Nishiyama, Akira; Minamino, Tetsuo

    2017-01-01

    Background Cardiac rupture is an important cause of death in the acute phase after myocardial infarction (MI). Macrophages play a pivotal role in cardiac remodeling after MI. Apoptosis inhibitor of macrophage (AIM) is secreted specifically by macrophages and contributes to macrophage accumulation in inflamed tissue by maintaining survival and recruiting macrophages. In this study, we evaluated the role of AIM in macrophage accumulation in the infarcted myocardium and cardiac rupture after MI. Methods and results Wild-type (WT) and AIM‒/‒ mice underwent permanent left coronary artery ligation and were followed-up for 7 days. Macrophage accumulation and phenotypes (M1 pro-inflammatory macrophage or M2 anti-inflammatory macrophage) were evaluated by immunohistological analysis and RT-PCR. Matrix metalloproteinase (MMP) activity levels were measured by gelatin zymography. The survival rate was significantly higher (81.1% vs. 48.2%, P<0.05), and the cardiac rupture rate was significantly lower in AIM‒/‒ mice than in WT mice (10.8% vs. 31.5%, P<0.05). The number of M1 macrophages and the expression levels of M1 markers (iNOS and IL-6) in the infarcted myocardium were significantly lower in AIM‒/‒ mice than in WT mice. In contrast, there was no difference in the number of M2 macrophages and the expression of M2 markers (Arg-1, CD206 and TGF-β1) between the two groups. The ratio of apoptotic macrophages in the total macrophages was significantly higher in AIM‒/‒ mice than in WT mice, although MCP-1 expression did not differ between the two groups. MMP-2 and 9 activity levels in the infarcted myocardium were significantly lower in AIM‒/‒ mice than in WT mice. Conclusions These findings suggest that AIM depletion decreases the levels of M1 macrophages, which are a potent source of MMP-2 and 9, in the infarcted myocardium in the acute phase after MI by promoting macrophage apoptosis, and leads to a decrease in the incidence of cardiac rupture and

  4. [Work-related rhinitis - Is it always an occupational disease?

    PubMed

    Salski, Witold; Wiszniewska, Marta; Salska, Agata; Tymoszuk, Diana; Walusiak-Skorupa, Jolanta

    2016-12-22

    Rhinitis is a chronic inflammatory disease of the upper respiratory tract, characterized by a high prevalence and a complex pathogenesis. Work-related rhinitis (WRR) can be divided into occupational rhinitis (OR) and work-exacerbated rhinitis (WER). It is not only considered as a disease entity but also in the context of medical certification as the allergic disease associated with occupational exposure. Epidemiology of work-related rhinitis has been found to vary depending on the occupation and specific exposure, on the other hand the prevalence data may be underestimated due to the lack of uniform diagnostic criteria. This paper reviews the issues comprising the pathogenesis, epidemiology, diagnosis and treatment of patients with work-related rhinitis. It also discusses the significance of the disease in occupational medicine, particularly in terms of preventive worker care, general principles of good practice in primary and secondary WRR prevention and the necessary directions of changes in medical certification in the cases of occupational rhinitis. Med Pr 2016;67(6):801-815. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  5. GDNF-expressing macrophages mitigate loss of dopamine neurons and improve Parkinsonian symptoms in MitoPark mice.

    PubMed

    Chen, Cang; Li, Xiuhua; Ge, Guo; Liu, Jingwei; Biju, K C; Laing, Suzette D; Qian, Yusheng; Ballard, Cori; He, Zhixu; Masliah, Eliezer; Clark, Robert A; O'Connor, Jason C; Li, Senlin

    2018-04-03

    Glial cell line-derived neurotrophic factor (GDNF) is the most potent neuroprotective agent tested in cellular and animal models of Parkinson's disease (PD). However, CNS delivery of GDNF is restricted by the blood-brain barrier (BBB). Using total body irradiation as transplant preconditioning, we previously reported that hematopoietic stem cell (HSC) transplantation (HSCT)-based macrophage-mediated gene therapy could deliver GDNF to the brain to prevent degeneration of nigrostriatal dopamine (DA) neurons in an acute murine neurotoxicity model. Here, we validate this therapeutic approach in a chronic progressive PD model - the MitoPark mouse, with head shielding to avoid inducing neuroinflammation and compromising BBB integrity. Bone marrow HSCs were transduced ex vivo with a lentiviral vector expressing macrophage promoter-driven GDNF and transplanted into MitoPark mice exhibiting well developed PD-like impairments. Transgene-expressing macrophages infiltrated the midbrains of MitoPark mice, but not normal littermates, and delivered GDNF locally. Macrophage GDNF delivery markedly improved both motor and non-motor symptoms, and dramatically mitigated the loss of both DA neurons in the substantia nigra and tyrosine hydroxylase-positive axonal terminals in the striatum. Our data support further development of this HSCT-based macrophage-mediated GDNF delivery approach in order to address the unmet need for a disease-modifying therapy for PD.

  6. Polarization of macrophages in the tumor microenvironment is influenced by EGFR signaling within colon cancer cells

    PubMed Central

    Zhang, Weina; Chen, Lechuang; Ma, Kai; Zhao, Yahui; Liu, Xianghe; Wang, Yu; Liu, Mei; Liang, Shufang; Zhu, Hongxia; Xu, Ningzhi

    2016-01-01

    Epidermal growth factor receptor (EGFR) is a target of colon cancer therapy, but the effects of this therapy on the tumor microenvironment remain poorly understood. Our in vivo studies showed that cetuximab, an anti-EGFR monoclonal antibody, effectively inhibited AOM/DSS-induced, colitis-associated tumorigenesis, downregulated M2-related markers, and decreased F4/80+/CD206+ macrophage populations. Treatment with conditioned medium of colon cancer cells increased macrophage expression of the M2-related markers arginase-1 (Arg1), CCL17, CCL22, IL-10 and IL-4. By contrast, conditioned medium of EGFR knockout colon cancer cells inhibited expression of these M2-related markers and induced macrophage expression of the M1-related markers inducible nitric oxide synthase (iNOS), IL-12, TNF-α and CCR7. EGFR knockout in colon cancer cells inhibited macrophage-induced promotion of xenograft tumor growth. Moreover, colon cancer-derived insulin-like growth factor-1 (IGF-1) increased Arg1 expression, and treatment with the IGF1R inhibitor AG1024 inhibited that increase. These results suggest that inhibition of EGFR signaling in colon cancer cells modulates cytokine secretion (e.g. IGF-1) and prevents M1-to-M2 macrophage polarization, thereby inhibiting cancer cell growth. PMID:27683110

  7. Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

    PubMed

    Takata, Kazuyuki; Kozaki, Tatsuya; Lee, Christopher Zhe Wei; Thion, Morgane Sonia; Otsuka, Masayuki; Lim, Shawn; Utami, Kagistia Hana; Fidan, Kerem; Park, Dong Shin; Malleret, Benoit; Chakarov, Svetoslav; See, Peter; Low, Donovan; Low, Gillian; Garcia-Miralles, Marta; Zeng, Ruizhu; Zhang, Jinqiu; Goh, Chi Ching; Gul, Ahmet; Hubert, Sandra; Lee, Bernett; Chen, Jinmiao; Low, Ivy; Shadan, Nurhidaya Binte; Lum, Josephine; Wei, Tay Seok; Mok, Esther; Kawanishi, Shohei; Kitamura, Yoshihisa; Larbi, Anis; Poidinger, Michael; Renia, Laurent; Ng, Lai Guan; Wolf, Yochai; Jung, Steffen; Önder, Tamer; Newell, Evan; Huber, Tara; Ashihara, Eishi; Garel, Sonia; Pouladi, Mahmoud A; Ginhoux, Florent

    2017-07-18

    Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Mitogen-activated protein kinase phosphatase-1 expression in macrophages is controlled by lymphocytes during macrophage activation.

    PubMed

    Luo, Chong; Yang, Xiqiang; Yao, Lan; Jiang, Liping; Liu, Wei; Li, Xin; Wang, Lijia

    2012-01-01

    The viewpoints on the control of innate immune cells by the adaptive immune system during sepsis remain controversial. Mitogen-activated protein kinase phosphatase-1 (MKP-1) is essential to the negative control of innate immunity and suppresses the activation of macrophages by inhibiting activated mitogen-activated protein kinase (MAPK). The purpose of the current study was to observe inflammatory response and macrophage activation in mice with severe combined immunodeficiency (SCID) with endotoxemia and to determine the role of MKP-1 in the control of macrophage activation by the adaptive immune system. Endotoxemia was induced in wild-type and SCID mice by an intraperitoneal injection of lipopolysaccharide (LPS), and all of the SCID mice died. SCID mice produced more inflammatory cytokines than BALB/c mice systemically and locally. TNF-α mRNA expression was higher and MKP-1 mRNA expression was lower in peritoneal macrophages (PMa) from SCID mice compared to PMa from wild-type mice after and even before LPS injection. Thioglycollate-stimulated PMa from wild-type mice were stimulated with LPS in vitro in the presence or absence of pan-T cells. The levels of TNF-α and IL-6 were higher in the supernatants from PMa cultured alone compared to PMa co-cultured with pan-T cells, and PMa MKP-1 mRNA and protein expression were higher when PMa were co-cultured with pan-T cells. Therefore, pan-T cells can up-regulate MKP-1 expression in macrophages and inhibit the secretion of inflammatory cytokines secretion by macrophages. In SCID mice, lymphocyte deficiency, especially T cell deficiency, causes insufficient MKP-1 expression in macrophages, which can be responsible for the severe inflammation and bad prognosis of septic SCID mice. MKP-1 plays an important role in the control of macrophage activation by the adaptive immune system.

  9. Interventions to prevent occupational noise-induced hearing loss.

    PubMed

    Tikka, Christina; Verbeek, Jos H; Kateman, Erik; Morata, Thais C; Dreschler, Wouter A; Ferrite, Silvia

    2017-07-07

    This is the second update of a Cochrane Review originally published in 2009. Millions of workers worldwide are exposed to noise levels that increase their risk of hearing disorders. There is uncertainty about the effectiveness of hearing loss prevention interventions. To assess the effectiveness of non-pharmaceutical interventions for preventing occupational noise exposure or occupational hearing loss compared to no intervention or alternative interventions. We searched the CENTRAL; PubMed; Embase; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; and OSH UPDATE to 3 October 2016. We included randomised controlled trials (RCT), controlled before-after studies (CBA) and interrupted time-series (ITS) of non-clinical interventions under field conditions among workers to prevent or reduce noise exposure and hearing loss. We also collected uncontrolled case studies of engineering controls about the effect on noise exposure. Two authors independently assessed study eligibility and risk of bias and extracted data. We categorised interventions as engineering controls, administrative controls, personal hearing protection devices, and hearing surveillance. We included 29 studies. One study evaluated legislation to reduce noise exposure in a 12-year time-series analysis but there were no controlled studies on engineering controls for noise exposure. Eleven studies with 3725 participants evaluated effects of personal hearing protection devices and 17 studies with 84,028 participants evaluated effects of hearing loss prevention programmes (HLPPs). Effects on noise exposure Engineering interventions following legislationOne ITS study found that new legislation in the mining industry reduced the median personal noise exposure dose in underground coal mining by 27.7 percentage points (95% confidence interval (CI) -36.1 to -19.3 percentage points) immediately after the implementation of stricter legislation. This roughly translates to a 4.5 dB(A) decrease in

  10. Monocyte to macrophage differentiation-associated (MMD) positively regulates ERK and Akt activation and TNF-α and NO production in macrophages.

    PubMed

    Liu, Qiang; Zheng, Jin; Yin, Dan-Dan; Xiang, Jie; He, Fei; Wang, Yao-Chun; Liang, Liang; Qin, Hong-Yan; Liu, Li; Liang, Ying-Min; Han, Hua

    2012-05-01

    Macrophage activation is modulated by both environmental cues and endogenous programs. In the present study, we investigated the role of a PAQR family protein, monocyte to macrophage differentiation-associated (MMD), in macrophage activation and unveiled its underlying molecular mechanism. Our results showed that while MMD expression could be detected in all tissues examined, its expression level is significantly up-regulated upon monocyte differentiation. Within cells, EGFP-MMD fusion protein could be co-localized to endoplasmic reticulum, mitochondria, Golgi apparatus, but not lysosomes and cytoplasm. MMD expression is up-regulated in macrophages after LPS stimulation, and this might be modulated by RBP-J, the critical transcription factor of Notch signaling. Overexpression of MMD in macrophages increased the production of TNF-α and NO upon LPS stimulation. We found that MMD overexpression enhanced ERK1/2 and Akt phosphorylation in macrophages after LPS stimulation. Blocking Erk or Akt by pharmacological agent reduced TNF-α or NO production in MMD-overexpressing macrophages, respectively. These results suggested that MMD modulates TNF-α and NO production in macrophages, and this process might involves Erk or Akt.

  11. Monoclonal antibody binding to the macrophage-specific receptor sialoadhesin alters the phagocytic properties of human and mouse macrophages.

    PubMed

    De Schryver, Marjorie; Cappoen, Davie; Elewaut, Dirk; Nauwynck, Hans J; Maes, Louis; Caljon, Guy; Cos, Paul; Delputte, Peter L

    2017-02-01

    Sialoadhesin (Sn) is a surface receptor expressed on macrophages in steady state conditions, but during inflammation, Sn can be upregulated both on macrophages and on circulating monocytes. It was shown for different species that Sn becomes internalized after binding with monoclonal antibodies. These features suggest that Sn is a potential target for immunotherapies. In this study, human and mouse macrophages were treated with anti-Sn monoclonal antibodies or F(ab') 2 fragments and the effect of their binding to Sn on phagocytosis was analyzed. Binding of antibodies to Sn resulted in delayed and reduced phagocytosis of fluorescent beads. No effect was observed on Fc-mediated phagocytosis or phagocytosis of bacteria by human macrophages. In contrast, an enhanced phagocytosis of bacteria by mouse macrophages was detected. These results showed that stimulation of Sn could have different effects on macrophage phagocytosis, depending both on the type of phagocytosis and cellular background. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Stimulatory Effects of Polysaccharide Fraction from Solanum nigrum on RAW 264.7 Murine Macrophage Cells

    PubMed Central

    Razali, Faizan Naeem; Ismail, Amirah; Abidin, Nurhayati Zainal; Shuib, Adawiyah Suriza

    2014-01-01

    The polysaccharide fraction from Solanum nigrum Linne has been shown to have antitumor activity by enhancing the CD4+/CD8+ ratio of the T-lymphocyte subpopulation. In this study, we analyzed a polysaccharide extract of S. nigrum to determine its modulating effects on RAW 264.7 murine macrophage cells since macrophages play a key role in inducing both innate and adaptive immune responses. Crude polysaccharide was extracted from the stem of S. nigrum and subjected to ion-exchange chromatography to partially purify the extract. Five polysaccharide fractions were then subjected to a cytotoxicity assay and a nitric oxide production assay. To further analyze the ability of the fractionated polysaccharide extract to activate macrophages, the phagocytosis activity and cytokine production were also measured. The polysaccharide fractions were not cytotoxic, but all of the fractions induced nitric oxide in RAW 264.7 cells. Of the five fractions tested, SN-ppF3 was the least toxic and also induced the greatest amount of nitric oxide, which was comparable to the inducible nitric oxide synthase expression detected in the cell lysate. This fraction also significantly induced phagocytosis activity and stimulated the production of tumor necrosis factor-α and interleukin-6. Our study showed that fraction SN-ppF3 could classically activate macrophages. Macrophage induction may be the manner in which polysaccharides from S. nigrum are able to prevent tumor growth. PMID:25299340

  13. Andrographolide Inhibits Oxidized LDL-Induced Cholesterol Accumulation and Foam Cell Formation in Macrophages.

    PubMed

    Lin, Hung-Chih; Lii, Chong-Kuei; Chen, Hui-Chun; Lin, Ai-Hsuan; Yang, Ya-Chen; Chen, Haw-Wen

    2018-01-01

    oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent

  14. Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor, macrophage receptor with collagenous structure.

    PubMed

    Murthy, Shubha; Larson-Casey, Jennifer L; Ryan, Alan J; He, Chao; Kobzik, Lester; Carter, A Brent

    2015-08-01

    Alternative activation of alveolar macrophages is linked to fibrosis following exposure to asbestos. The scavenger receptor, macrophage receptor with collagenous structure (MARCO), provides innate immune defense against inhaled particles and pathogens; however, a receptor for asbestos has not been identified. We hypothesized that MARCO acts as an initial signaling receptor for asbestos, polarizes macrophages to a profibrotic M2 phenotype, and is required for the development of asbestos-induced fibrosis. Compared with normal subjects, alveolar macrophages isolated from patients with asbestosis express higher amounts of MARCO and have greater profibrotic polarization. Arginase 1 (40-fold) and IL-10 (265-fold) were higher in patients. In vivo, the genetic deletion of MARCO attenuated the profibrotic environment and pulmonary fibrosis in mice exposed to chrysotile. Moreover, alveolar macrophages from MARCO(-/-) mice polarize to an M1 phenotype, whereas wild-type mice have higher Ym1 (>3.0-fold) and nearly 7-fold more active TGF-β1 in bronchoalveolar lavage (BAL) fluid (BALF). Arg(432) and Arg(434) in domain V of MARCO are required for the polarization of macrophages to a profibrotic phenotype as mutation of these residues reduced FIZZ1 expression (17-fold) compared with cells expressing MARCO. These observations demonstrate that a macrophage membrane protein regulates the fibrotic response to lung injury and suggest a novel target for therapeutic intervention. © FASEB.

  15. Dihydro-CDDO-trifluoroethyl amide suppresses inflammatory responses in macrophages via activation of Nrf2

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Bin; Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208; Abdalrahman, Akram

    2014-02-21

    Highlights: • Dh404 suppresses the expression of a selected set of pro-inflammatory cytokines in inflamed macrophages via activating Nrf2. • Dh404 activates Nrf2 while keeping Keap1 function intact in macrophages. • Dh404 minimally regulates NF-κB pathway in macrophages. - Abstract: Nuclear factor erythroid 2-related factor (Nrf2) is the major regulator of cellular defenses against various pathological stresses in a variety of organ systems, thus Nrf2 has evolved to be an attractive drug target for the treatment and/or prevention of human disease. Several synthetic oleanolic triterpenoids including dihydro-CDDO-trifluoroethyl amide (dh404) appear to be potent activators of Nrf2 and exhibit chemopreventive promisesmore » in multiple disease models. While the pharmacological efficacy of Nrf2 activators may be dependent on the nature of Nrf2 activation in specific cell types of target organs, the precise role of Nrf2 in mediating biological effects of Nrf2 activating compounds in various cell types remains to be further explored. Herein we report a unique and Nrf2-dependent anti-inflammatory profile of dh404 in inflamed macrophages. In lipopolysaccharide (LPS)-inflamed RAW264.7 macrophages, dh404 dramatically suppressed the expression of pro-inflammatory cytokines including inducible nitric oxide synthase (iNOS), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1 beta (MIP-1β), while minimally regulating the expression of interleulin-6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNFα). Dh404 potently activated Nrf2 signaling; however, it did not affect LPS-induced NF-κB activity. Dh404 did not interrupt the interaction of Nrf2 with its endogenous inhibitor Kelch-like ECH associating protein 1 (Keap1) in macrophages. Moreover, knockout of Nrf2 blocked the dh404-induced anti-inflammatory responses in LPS-inflamed macrophages. These results demonstrated that dh404 suppresses pro-inflammatory responses in macrophages via an

  16. Immunological characterization of pulmonary intravascular macrophages

    NASA Technical Reports Server (NTRS)

    Chitko-McKown, C. G.; Reddy, D. N.; Chapes, S. K.; McKown, R. D.; Blecha, F.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.

  17. Macrophage heterogeneity and cholesterol homeostasis: classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL.

    PubMed

    Chu, Eugene M; Tai, Daven C; Beer, Jennifer L; Hill, John S

    2013-02-01

    Macrophages are centrally involved during atherosclerosis development and are the predominant cell type that accumulates cholesterol in the plaque. Macrophages however, are heterogeneous in nature reflecting a variety of microenvironments and different phenotypes may be more prone to contribute towards atherosclerosis progression. Using primary human monocyte-derived macrophages, we sought to evaluate one aspect of atherogenic potential of different macrophage phenotypes by determining their propensity to associate with and accumulate oxidized low density lipoprotein (oxLDL). Classically-activated macrophages treated simultaneously with interferon γ (IFNγ) and tumor necrosis factor α (TNFα) associated with less oxLDL and accumulated less cholesterol compared to untreated controls. The combined treatment of IFNγ and TNFα reduced the mRNA expression of CD36 and the expression of both cell surface CD36 and macrophage scavenger receptor 1 (MSR1) protein. Under oxLDL loaded conditions, IFNγ and TNFα did not reduce macrophage protein expression of the transcription factor peroxisome proliferator-actived receptor γ (PPARγ) which is known to positively regulate CD36 expression. However, macrophages treated with IFNγ attenuated the ability of the PPARγ-specific agonist rosiglitazone from upregulating cell surface CD36 protein expression. Our results demonstrate that the observed reduction of cholesterol accumulation in macrophages treated with IFNγ and TNFα following oxLDL treatment was due at least in part to reduced cell surface CD36 and MSR1 protein expression. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Modulating macrophage response to biomaterials

    NASA Astrophysics Data System (ADS)

    Zaveri, Toral

    Macrophages recruited to the site of biomaterial implantation are the primary mediators of the chronic foreign body response to implanted materials. Since foreign body response limits performance and functional life of numerous implanted biomaterials/medical devices, various approaches have been investigated to modulate macrophage interactions with biomaterial surfaces to mitigate this response. In this work we have explored two independent approaches to modulate the macrophage inflammatory response to biomaterials. The first approach targets surface integrins, cell surface receptors that mediate cell adhesion to biomaterials through adhesive proteins spontaneously adsorbed on biomaterial surfaces. The second approach involves surface modification of biomaterials using nanotopographic features since nanotopography has been reported to modulate cell adhesion and viability in a cell type-dependent manner. More specifically, Zinc Oxide (ZnO) nanorod surface was investigated for its role in modulating macrophage adhesion and survival in vitro and foreign body response in vivo. For the first approach, we have investigated the role of integrin Mac-1 and RGD-binding integrins in the in-vivo osteolysis response and macrophage inflammatory processes of phagocytosis as well as inflammatory cytokine secretion in response to particulate biomaterials. We have also investigated the in vivo foreign body response (FBR) to subcutaneously implanted biomaterials by evaluating the thickness of fibrous capsule formed around the implants after 2 weeks of implantation. The role of Mac-1 integrin was isolated using a Mac-1 KO mouse and comparing it to a WT control. The role of RGD binding integrins in FBR was investigated by coating the implanted biomaterial with ELVAX(TM) polymer loaded with Echistatin which contains the RGD sequence. For the in-vivo osteolysis study and to study the in-vitro macrophage response to particulate biomaterials, we used the RGD peptide encapsulated in ELVAX

  19. Ability of rabbit alveolar macrophages to dissolve metals.

    PubMed

    Lundborg, M; Lind, B; Camner, P

    1984-01-01

    Manganese dioxide particles, 0.1-0.5 micron, were added to samples of 2-3 X 10(6) rabbit alveolar macrophages. The amount of manganese added and dissolved from the particles, over periods of 0, 1, 3, and 5 days, was determined by flame atomic absorption spectrophotometry. Macrophages from six rabbits received about 10 micrograms of Mn, macrophages from two rabbits about 30 micrograms, and macrophages from another two rabbits about 100 micrograms. Over periods of 1, 3, and 5 days the macrophages in all three dose groups dissolved two to three times more Mn than was dissolved in control experiments. In control experiments solubility was studied in the medium without macrophages. Macrophages cultivated 3 days before the addition of MnO2 dissolved the particles within another 2 days to an extent similar to that in the control experiments. The ability of the macrophages to dissolve MnO2 particles might be related to the low pH values in the phagosomes. Studies of the ability of macrophages from various species to dissolve metal particles as well as of pH values in their phagosomes might lead to a better understanding of alveolar clearance of metal particles.

  20. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration.

    PubMed

    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter; Schulze, Tobias

    2017-01-01

    Introduction . Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P 1-5 ) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods . Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results . All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P 1 . In contrast, M1-polarized macrophages significantly downregulated S1P 4 . The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion . The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.

  1. Midkine is expressed by infiltrating macrophages in in-stent restenosis in hypercholesterolemic rabbits.

    PubMed

    Narita, Hiroshi; Chen, Sen; Komori, Kimihiro; Kadomatsu, Kenji

    2008-06-01

    is more prolonged and the accumulation of macrophages is more abundant in stent-injured vessel. We found here that macrophages are the major source of midkine in the atherosclerotic neointima of in-stent restenosis in hypercholesterolemic rabbits. Our data suggest that midkine has an important role in in-stent restenosis of atherosclerotic vessels and is a candidate molecular target to prevent in-stent restenosis.

  2. Work-related accidents and occupational diseases in veterinarians and their staff.

    PubMed

    Nienhaus, Albert; Skudlik, Christoph; Seidler, Andreas

    2005-04-01

    We assessed the occupational hazards in veterinary practice by analysing accident insurance data in order to stimulate strategies to prevent occupational accidents and diseases in veterinarians and their staff. Approximately 10,000 veterinary practices comprising about 27,500 veterinarians and their staff are covered by the Institution of Statutory Accident Insurance of the Health and Welfare Service (BGW). Each year about 2,000 accident and occupational disease claims are filed by these veterinarians and their staff. The claims for the 5-year period from 1998 to 2002 are analysed in this paper. For 2002, the incidence rate for accidents in the workplace was 105.4 per 1,000 full-time workers, a rate 2.9-times higher than for general practitioners of human medicine. When only severe accidents resulting in a loss of work time of more than 3 days were analysed, the relative risk increased to 9.2. Approximately 66% of the reported accidents are due to scratches, bites, or kicks from animals. Claims of occupational disease are filed 2.7-times more often by veterinarians and their staff than by general practitioners and their staff. The occupational diseases filed most often concern the skin (39%), followed by allergic respiratory diseases (30.5%), and infectious diseases (19.1%). Prevention strategies for veterinarians should focus on accidents caused by animals. The prevention of occupational diseases should focus on skin diseases, respiratory disease, and infections.

  3. Suppressive effects of ketamine on macrophage functions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang Yi; Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Chen, T.-L.

    2005-04-01

    Ketamine is an intravenous anesthetic agent. Clinically, induction of anesthesia with ketamine can cause immunosuppression. Macrophages play important roles in host defense. In this study, we attempted to evaluate the effects of ketamine on macrophage functions and its possible mechanism using mouse macrophage-like Raw 264.7 cells as the experimental model. Exposure of macrophages to 10 and 100 {mu}M ketamine, which correspond to 0.1 and 1 times the clinically relevant concentration, for 1, 6, and 24 h had no effect on cell viability or lactate dehydrogenase release. When the administered concentration reached 1000 {mu}M, ketamine caused a release of lactate dehydrogenasemore » and cell death. Ketamine, at 10 and 100 {mu}M, did not affect the chemotactic activity of macrophages. Administration of 1000 {mu}M ketamine in macrophages resulted in a decrease in cell migration. Treatment of macrophages with ketamine reduced phagocytic activities. The oxidative ability of macrophages was suppressed by ketamine. Treatment with lipopolysaccharide induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA in macrophages. Administration of ketamine alone did not influence TNF-{alpha}, IL-1{beta}, or IL-6 mRNA production. Meanwhile, cotreatment with ketamine and lipopolysaccharide significantly inhibited lipopolysaccharide-induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA levels. Exposure to ketamine led to a decrease in the mitochondrial membrane potential. However, the activity of mitochondrial complex I NADH dehydrogenase was not affected by ketamine. This study shows that a clinically relevant concentration of ketamine (100 {mu}M) can suppress macrophage function of phagocytosis, its oxidative ability, and inflammatory cytokine production possibly via reduction of the mitochondrial membrane potential instead of direct cellular toxicity.« less

  4. Occupational ladder fall injuries - United States, 2011.

    PubMed

    Socias, Christina M; Chaumont Menéndez, Cammie K; Collins, James W; Simeonov, Peter

    2014-04-25

    Falls remain a leading cause of unintentional injury mortality nationwide [corrected].Among workers, approximately 20% of fall injuries involve ladders. Among construction workers, an estimated 81% of fall injuries treated in U.S. emergency departments (EDs) involve a ladder. To fully characterize fatal and nonfatal injuries associated with ladder falls among workers in the United States, CDC's National Institute for Occupational Safety and Health (NIOSH) analyzed data across multiple surveillance systems: 1) the Census of Fatal Occupational Injuries (CFOI), 2) the Survey of Occupational Injuries and Illnesses (SOII), and 3) the National Electronic Injury Surveillance System-occupational supplement (NEISS-Work). In 2011, work-related ladder fall injuries (LFIs) resulted in 113 fatalities (0.09 per 100,000 full-time equivalent [FTE] workers), an estimated 15,460 nonfatal injuries reported by employers that involved ≥1 days away from work (DAFW), and an estimated 34,000 nonfatal injuries treated in EDs. Rates for nonfatal, work-related, ED-treated LFIs were higher (2.6 per 10,000 FTE) than those for such injuries reported by employers (1.2 per 10,000 FTE). LFIs represent a substantial public health burden of preventable injuries for workers. Because falls are the leading cause of work-related injuries and deaths in construction, NIOSH, the Occupational Safety and Health Administration, and the Center for Construction Research and Training are promoting a national campaign to prevent workplace falls. NIOSH is also developing innovative technologies to complement safe ladder use.

  5. Occupational lung cancer in US women, 1984-1998.

    PubMed

    Robinson, Cynthia F; Sullivan, Patricia A; Li, Jia; Walker, James T

    2011-02-01

    Lung cancer is the leading cause of cancer death in US women, accounting for 72,130 deaths in 2006. In addition to smoking cessation, further reduction of the burden of lung cancer mortality can be made by preventing exposure to occupational lung carcinogens. Data for occupational exposures and health outcomes of US working women are limited. Population-based mortality data for 4,570,711 women who died between 1984 and 1998 in 27 US States were used to evaluate lung cancer proportionate mortality over time by the usual occupation and industry reported on death certificates. Lung cancer proportionate mortality ratios were adjusted for smoking, using data from the National Health Interview Survey (NHIS) and the American Cancer Society's Cancer Prevention Study II. Analyses revealed that 194,382 white, 18,225 Black and 1,515 Hispanic women died 1984-1998 with lung cancer reported as the underlying cause of death. Following adjustment for smoking, significant excess proportionate lung cancer mortality was observed among US women working in the US manufacturing; transportation; retail trade; agriculture, forestry, and fishing; and nursing/personal care industries. Women employed in precision production, technical, managerial, professional specialty, and administrative occupations experienced some of the highest significantly excess proportionate lung cancer mortality during 1984-1998. The results of our study point to significantly elevated risks for lung cancer after adjustment for smoking among women in several occupations and industries. Because 6-17% of lung cancer in US males is attributable to known exposures to occupational carcinogens, and since synergistic interactions between cigarette smoke and other occupational lung carcinogens have been noted, it is important to continue research into the effects of occupational exposures on working men and women. Copyright © 2010 Wiley-Liss, Inc.

  6. Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia

    PubMed Central

    Amici, Stephanie A.; Dong, Joycelyn; Guerau-de-Arellano, Mireia

    2017-01-01

    Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2 macrophages has been widely used. However, the complexity of macrophage function can only be achieved by the existence of varied, plastic and tridimensional macrophage phenotypes. Understanding how tissue macrophages integrate environmental signals via molecular programs to define pathogen/injury inflammatory responses provides an opportunity to better understand the multilayered nature of macrophages, as well as target and modulate cellular programs to control excessive inflammation. This is particularly important in MS and other neuroinflammatory diseases, where chronic inflammatory macrophage and microglial responses may contribute to pathology. Here, we perform a comprehensive review of our current understanding of how molecular pathways modulate tissue macrophage phenotype, covering both classic pathways and the emerging role of microRNAs, receptor-tyrosine kinases and metabolism in macrophage phenotype. In addition, we discuss pathway parallels in microglia, novel markers helpful in the identification of peripheral macrophages versus microglia and markers linked to their phenotype. PMID:29176977

  7. The macrophage marker translocator protein (TSPO) is down-regulated on pro-inflammatory ‘M1’ human macrophages

    PubMed Central

    Mandhair, Harpreet; Smyth, Erica; Dakin, Stephanie Georgina; Kiriakidis, Serafim; Wells, Lisa; Owen, David; Sabokbar, Afsie; Taylor, Peter

    2017-01-01

    The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis. Here, we utilized three human sources of monocyte derived macrophages (MDM), from THP-1 monocytes, healthy peripheral blood monocytes and synovial fluid monocytes from patients with rheumatoid arthritis, to undertake a detailed investigation of TSPO expression in activated macrophages. In this work, we demonstrate a consistent down-regulation of TSPO mRNA and protein in macrophages activated to a pro-inflammatory, or ‘M1’ phenotype. Conversely, stimulation of macrophages to an M2 phenotype with IL-4, dexamethasone or TGF-β1 did not alter TSPO expression, regardless of MDM source. The reasons for this are uncertain, but our study findings add some supporting evidence for recent investigations concluding that TSPO may be involved in negative regulation of inflammatory responses in macrophages. PMID:28968465

  8. AIDS control and the workplace: the role of occupational health services in South Africa.

    PubMed

    London, L

    1998-01-01

    AIDS interventions typically fail to address the disjuncture between private behaviors and the social determinants of HIV infection. Data from a telephone survey of manufacturing companies and a postal survey of occupational health nurses in the Western Cape, South Africa, were used to explore the possible role of occupational health services in prevention and control of AIDS. The author found limited evidence of worker involvement in AIDS programs, particularly in companies with occupational health professionals. The management of sexually transmitted diseases was incomplete. Mandatory pre-employment testing of workers for HIV was not widespread. Respondents' opinions on priorities for AIDS prevention and control reflected a preoccupation with knowledge transfer. To ensure their effectiveness, workplace AIDS programs must improve worker participation and integrate AIDS prevention in general workplace health and safety programs. In addition, education programs must develop objectives within a critical theoretical understanding of the behavioral issues relevant to AIDS prevention, and must emphasize the empowerment of women in the workplace. In the context of the present restructuring of health services in South Africa, occupational health services, using the strategies outlined, can make a major contribution to national AIDS prevention and control.

  9. Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation

    PubMed Central

    Zhang, Yang; Liu, Gongjian; Dull, Randal O.; Schwartz, David E.

    2014-01-01

    The inflammatory response is a primary mechanism in the pathogenesis of ventilator-induced lung injury. Autophagy is an essential, homeostatic process by which cells break down their own components. We explored the role of autophagy in the mechanisms of mechanical ventilation-induced lung inflammatory injury. Mice were subjected to low (7 ml/kg) or high (28 ml/kg) tidal volume ventilation for 2 h. Bone marrow-derived macrophages transfected with a scrambled or autophagy-related protein 5 small interfering RNA were administered to alveolar macrophage-depleted mice via a jugular venous cannula 30 min before the start of the ventilation protocol. In some experiments, mice were ventilated in the absence and presence of autophagy inhibitors 3-methyladenine (15 mg/kg ip) or trichostatin A (1 mg/kg ip). Mechanical ventilation with a high tidal volume caused rapid (within minutes) activation of autophagy in the lung. Conventional transmission electron microscopic examination of lung sections showed that mechanical ventilation-induced autophagy activation mainly occurred in lung macrophages. Autophagy activation in the lungs during mechanical ventilation was dramatically attenuated in alveolar macrophage-depleted mice. Selective silencing of autophagy-related protein 5 in lung macrophages abolished mechanical ventilation-induced nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation and lung inflammatory injury. Pharmacological inhibition of autophagy also significantly attenuated the inflammatory responses caused by lung hyperinflation. The activation of autophagy in macrophages mediates early lung inflammation during mechanical ventilation via NLRP3 inflammasome signaling. Inhibition of autophagy activation in lung macrophages may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury. PMID:24838752

  10. Metabolism of phenol and hydroquinone to reactive products by macrophage peroxidase or purified prostaglandin H synthase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schlosser, M.J.; Shurina, R.D.; Kalf, G.F.

    1989-07-01

    Macrophages, an important cell-type of the bone marrow stroma, are possible targets of benzene toxicity because they contain relatively large amounts of prostaglandin H synthase (PHS), which is capable of metabolizing phenolic compounds to reactive species. PHS also catalyzes the production of prostaglandins, negative regulators of myelopoiesis. Studies indicate that the phenolic metabolites of benzene are oxidized in bone marrow to reactive products via peroxidases. With respect to macrophages, PHS peroxidase is implicated, as in vivo benzene-induced myelotoxicity is prevented by low doses of nonsteroidal anti-inflammatory agents, drugs that inhibit PHS. Incubations of either 14C-phenol or 14C-hydroquinone with a lysatemore » of macrophages collected from mouse peritoneum (greater than 95% macrophages), resulted in an irreversible binding to protein that was dependent upon H2O2, incubation time, and concentration of radiolabel. Production of protein-bound metabolites from phenol or hydroquinone was inhibited by the peroxidase inhibitor aminotriazole. Protein binding from 14C-phenol also was inhibited by 8 microM hydroquinone, whereas binding from 14C-hydroquinone was stimulated by 5 mM phenol. The nucleophile cysteine inhibited protein binding of both phenol and hydroquinone and increased the formation of radiolabeled water-soluble metabolites. Similar to the macrophage lysate, purified PHS also catalyzed the conversion of phenol to metabolites that bound to protein and DNA; this activation was both H2O2- and arachidonic acid-dependent. These results indicate a role for macrophage peroxidase, possibly PHS peroxidase, in the conversion of phenol and hydroquinone to reactive metabolites and suggest that the macrophage should be considered when assessing the hematopoietic toxicity of benzene.« less

  11. Effect of age on marrow macrophage number and function.

    PubMed

    Wang, C Q; Udupa, K B; Xiao, H; Lipschitz, D A

    1995-10-01

    Employing flow cytometry and a monoclonal antibody against the murine macrophage antigen, Mac-1, we found a significant increase in the number of marrow macrophages in aged mice. This was reflected as significant increase with age in the number of alpha-naphthyl acetate esterase positive cells, as well as in colony forming unit-macrophage (CFU-M) progenitor cells. Macrophages from the marrow of old mice generated significantly less tumor necrosis factor alpha (TNF alpha) than did macrophages from young mice, either spontaneously or when activated by granulocyte-macrophage colony stimulating factor (GM-CSF). Furthermore, conditioned medium (CM) derived from either marrow or peritoneal macrophages of old mice caused less suppression of burst forming unit-erythroid (BFU-E) colony growth than did CM obtained from young mice. Aging, therefore, is associated with an increase in the number of marrow macrophages that have an impaired ability to generate or release cytokines. The increase in macrophage number may reflect a compensation for their reduced function. Altered macrophage number and function may contribute to the age-related decline in hematopoietic reserve capacity.

  12. Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF-1-induced macrophage migration.

    PubMed

    Dwyer, Amy R; Mouchemore, Kellie A; Steer, James H; Sunderland, Andrew J; Sampaio, Natalia G; Greenland, Eloise L; Joyce, David A; Pixley, Fiona J

    2016-07-01

    A major role of colony-stimulating factor-1 is to stimulate the differentiation of mononuclear phagocytic lineage cells into adherent, motile, mature macrophages. The colony-stimulating factor-1 receptor transduces colony-stimulating factor-1 signaling, and we have shown previously that phosphatidylinositol 3-kinase p110δ is a critical mediator of colony-stimulating factor-1-stimulated motility through the colony-stimulating factor-1 receptor pY721 motif. Src family kinases are also implicated in the regulation of macrophage motility and in colony-stimulating factor-1 receptor signaling, although functional redundancy of the multiple SFKs expressed in macrophages makes it challenging to delineate their specific functions. We report a comprehensive analysis of individual Src family kinase expression in macrophage cell lines and primary macrophages and demonstrate colony-stimulating factor-1-induced changes in Src family kinase subcellular localization, which provides clues to their distinct and redundant functions in macrophages. Moreover, expression of individual Src family kinases is both species specific and dependent on colony-stimulating factor-1-induced macrophage differentiation. Hck associated with the activated colony-stimulating factor-1 receptor, whereas Lyn associated with the receptor in a constitutive manner. Consistent with this, inhibitor studies revealed that Src family kinases were important for both colony-stimulating factor-1 receptor activation and colony-stimulating factor-1-induced macrophage spreading, motility, and invasion. Distinct colony-stimulating factor-1-induced changes in the subcellular localization of individual SFKs suggest specific roles for these Src family kinases in the macrophage response to colony-stimulating factor-1. © Society for Leukocyte Biology.

  13. Accumulation of M1-like macrophages in type 2 diabetic islets is followed by a systemic shift in macrophage polarization.

    PubMed

    Cucak, Helena; Grunnet, Lars Groth; Rosendahl, Alexander

    2014-01-01

    Human T2D is characterized by a low-grade systemic inflammation, loss of β-cells, and diminished insulin production. Local islet immunity is still poorly understood, and hence, we evaluated macrophage subpopulations in pancreatic islets in the well-established murine model of T2D, the db/db mouse. Already at 8 weeks of disease, on average, 12 macrophages were observed in the diabetic islets, whereas only two were recorded in the nondiabetic littermates. On a detailed level, the islet resident macrophages increased fourfold compared with nondiabetic littermates, whereas a pronounced recruitment (eightfold) of a novel subset of macrophages (CD68+F4/80-) was observed. The majority of the CD68+F4/80+ but only 40% of the CD68+F4/80- islet macrophages expressed CD11b. Both islet-derived macrophage subsets expressed moderate MHC-II, high galectin-3, and low CD80/CD86 levels, suggesting the cells to be macrophages rather than DCs. On a functional level, the vast majority of the macrophages in the diabetic islets was of the proinflammatory, M1-like phenotype. The systemic immunity in diabetic animals was characterized by a low-grade inflammation with elevated cytokine levels and increase of splenic cytokine, producing CD68+F4/80- macrophages. In late-stage diabetes, the cytokine signature changed toward a TGF-β-dominated profile, coinciding with a significant increase of galectin-3-positive macrophages in the spleen. In summary, our results show that proinflammatory M1-like galectin-3+ CD80/CD86(low) macrophages invade diabetic islets. Moreover, the innate immunity matures in a diabetes-dependent manner from an initial proinflammatory toward a profibrotic phenotype, supporting the concept that T2D is an inflammatory disease.

  14. Macrophages: An Inflammatory Link between Angiogenesis and Lymphangiogenesis

    PubMed Central

    Corliss, Bruce A.; Azimi, Mohammad S.; Munson, Jenny; Peirce, Shayn M.; Murfee, Walter Lee

    2015-01-01

    Angiogenesis and lymphangiogenesis often occur in response to tissue injury or in the presence of pathology (e.g. cancer), and it is these types of environments in which macrophages are activated and increased in number. Moreover, the blood vascular microcirculation and the lymphatic circulation serve as the conduits for entry and exit for monocyte-derived macrophages in nearly every tissue and organ. Macrophages both affect and are affected by the vessels through which they travel. Therefore, it is not surprising that examination of macrophage behaviors in both angiogenesis and lymphangiogenesis has yielded interesting observations that suggest macrophages may be key regulators of these complex growth and remodeling processes. In this review, we will take a closer look at macrophages through the lens of angiogenesis and lymphangiogenesis, examining how their dynamic behaviors may regulate vessel sprouting and function. We present macrophages as a cellular link that spatially and temporally connects angiogenesis with lymphangiogenesis, in both physiological growth and in pathological adaptations, such as tumorigenesis. As such, attempts to therapeutically target macrophages in order to affect these processes may be particularly effective, and studying macrophages in both settings will accelerate the field’s understanding of this important cell type in health and disease. PMID:26614117

  15. M2 Macrophages Play Critical Roles in Progression of Inflammatory Liver Disease in Hepatitis C Virus Transgenic Mice.

    PubMed

    Ohtsuki, Takahiro; Kimura, Kiminori; Tokunaga, Yuko; Tsukiyama-Kohara, Kyoko; Tateno, Chise; Hayashi, Yukiko; Hishima, Tsunekazu; Kohara, Michinori

    2016-01-01

    Macrophages in liver tissue are widely defined as important inflammatory cells in chronic viral hepatitis due to their proinflammatory activity. We reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) play significant roles in causing chronic hepatitis in hepatitis C virus (HCV) transgenic mice (S. Sekiguchi et al., PLoS One 7:e51656, 2012, http://dx.doi.org/10.1371/journal.pone.0051656). In addition, we showed that recombinant vaccinia viruses expressing an HCV nonstructural protein (rVV-N25) could protect against the progression of chronic hepatitis by suppression of macrophage activation. Here, we focus on the role of macrophages in liver disease progression in HCV transgenic mice and examine characteristic features of macrophages following rVV-N25 treatment. The number of CD11b(+) F4/80(+) CD11c(-) CD206(+) (M2) macrophages in the liver of HCV transgenic mice was notably increased compared to that of age-matched control mice. These M2 macrophages in the liver produced elevated levels of IL-6 and TNF-α. rVV-N25 infection suppressed the number and activation of M2 macrophages in liver tissue. These results suggested that inflammatory cytokines produced by M2-like macrophages contribute to the induction of chronic liver inflammation in HCV transgenic mice. Moreover, the therapeutic effect of rVV-N25 might be induced by the suppression of the number and activation of hepatic macrophages. HCV causes persistent infections that can lead to chronic liver diseases, liver fibrosis, and hepatocellular carcinoma; the search for an HCV curative is the focus of ongoing research. Recently, effective anti-HCV drugs have been developed; however, vaccine development still is required for the prevention and therapy of infection by this virus. We demonstrate here that M2 macrophages are important for the pathogenesis of HCV-caused liver diseases and additionally show that M2 macrophages contribute to the therapeutic mechanism observed following r

  16. M2 Macrophages Play Critical Roles in Progression of Inflammatory Liver Disease in Hepatitis C Virus Transgenic Mice

    PubMed Central

    Ohtsuki, Takahiro; Kimura, Kiminori; Tokunaga, Yuko; Tsukiyama-Kohara, Kyoko; Tateno, Chise; Hayashi, Yukiko; Hishima, Tsunekazu

    2015-01-01

    ABSTRACT Macrophages in liver tissue are widely defined as important inflammatory cells in chronic viral hepatitis due to their proinflammatory activity. We reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) play significant roles in causing chronic hepatitis in hepatitis C virus (HCV) transgenic mice (S. Sekiguchi et al., PLoS One 7:e51656, 2012, http://dx.doi.org/10.1371/journal.pone.0051656). In addition, we showed that recombinant vaccinia viruses expressing an HCV nonstructural protein (rVV-N25) could protect against the progression of chronic hepatitis by suppression of macrophage activation. Here, we focus on the role of macrophages in liver disease progression in HCV transgenic mice and examine characteristic features of macrophages following rVV-N25 treatment. The number of CD11b+ F4/80+ CD11c− CD206+ (M2) macrophages in the liver of HCV transgenic mice was notably increased compared to that of age-matched control mice. These M2 macrophages in the liver produced elevated levels of IL-6 and TNF-α. rVV-N25 infection suppressed the number and activation of M2 macrophages in liver tissue. These results suggested that inflammatory cytokines produced by M2-like macrophages contribute to the induction of chronic liver inflammation in HCV transgenic mice. Moreover, the therapeutic effect of rVV-N25 might be induced by the suppression of the number and activation of hepatic macrophages. IMPORTANCE HCV causes persistent infections that can lead to chronic liver diseases, liver fibrosis, and hepatocellular carcinoma; the search for an HCV curative is the focus of ongoing research. Recently, effective anti-HCV drugs have been developed; however, vaccine development still is required for the prevention and therapy of infection by this virus. We demonstrate here that M2 macrophages are important for the pathogenesis of HCV-caused liver diseases and additionally show that M2 macrophages contribute to the therapeutic mechanism

  17. Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages.

    PubMed

    Lichtenstein, Laeticia; Mattijssen, Frits; de Wit, Nicole J; Georgiadi, Anastasia; Hooiveld, Guido J; van der Meer, Roelof; He, Yin; Qi, Ling; Köster, Anja; Tamsma, Jouke T; Tan, Nguan Soon; Müller, Michael; Kersten, Sander

    2010-12-01

    Dietary saturated fat is linked to numerous chronic diseases, including cardiovascular disease. Here we study the role of the lipoprotein lipase inhibitor Angptl4 in the response to dietary saturated fat. Strikingly, in mice lacking Angptl4, saturated fat induces a severe and lethal phenotype characterized by fibrinopurulent peritonitis, ascites, intestinal fibrosis, and cachexia. These abnormalities are preceded by a massive acute phase response induced by saturated but not unsaturated fat or medium-chain fat, originating in mesenteric lymph nodes (MLNs). MLNs undergo dramatic expansion and contain numerous lipid-laden macrophages. In peritoneal macrophages incubated with chyle, Angptl4 dramatically reduced foam cell formation, inflammatory gene expression, and chyle-induced activation of ER stress. Induction of macrophage Angptl4 by fatty acids is part of a mechanism that serves to reduce postprandial lipid uptake from chyle into MLN-resident macrophages by inhibiting triglyceride hydrolysis, thereby preventing macrophage activation and foam cell formation and protecting against progressive, uncontrolled saturated fat-induced inflammation. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Origins of Brain Tumor Macrophages.

    PubMed

    De Palma, Michele

    2016-12-12

    The ontogeny of brain-tumor-associated macrophages is poorly understood. New findings indicate that both resident microglia and blood-derived monocytes generate the pool of macrophages that infiltrate brain tumors of either primary or metastatic origin. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Outbreak of Occupational Brucellosis at a Pharmaceutical Factory in Southeast China.

    PubMed

    Zhan, B D; Wang, S Q; Lai, S M; Lu, Y; Shi, X G; Cao, G P; Hu, X L; Zheng, C J; Yu, Z Y; Zhang, J M; Fang, C F; Gong, Z Y

    2017-09-01

    Brucellosis is an occupational disease affecting workers in butcher shops, the milking and dairy product industry, causing more than 500 000 new cases around the world. As a national statutory B infectious disease in China, morbidity of brucellosis is rapidly increasing in recent years. We report an occupational outbreak of brucellosis infection in a pharmaceutical factory. Exposure was a result of manual operation in the process line, close contact with sheep placentas, insufficient disinfection and repeated using of protective suits and infected by aerosol dissemination. Improved preventive methods, appropriate public health measures and spread of health education would be helpful to prevent the occupational outbreak of brucellosis in future. © 2016 Blackwell Verlag GmbH.

  20. Conditional Macrophage Depletion Increases Inflammation and Does Not Inhibit the Development of Osteoarthritis in Obese Macrophage Fas-Induced Apoptosis-Transgenic Mice.

    PubMed

    Wu, Chia-Lung; McNeill, Jenna; Goon, Kelsey; Little, Dianne; Kimmerling, Kelly; Huebner, Janet; Kraus, Virginia; Guilak, Farshid

    2017-09-01

    To investigate whether short-term, systemic depletion of macrophages can mitigate osteoarthritis (OA) following injury in the setting of obesity. CSF-1R-GFP+ macrophage Fas-induced apoptosis (MaFIA)-transgenic mice that allow conditional depletion of macrophages were placed on a high-fat diet and underwent surgery to induce knee OA. A small molecule (AP20187) was administrated to deplete macrophages in MaFIA mice. The effects of macrophage depletion on acute joint inflammation, OA severity, and arthritic bone changes were evaluated using histology and micro-computed tomography. Immunohistochemical analysis was performed to identify various immune cells. The levels of serum and synovial fluid cytokines were also measured. Macrophage-depleted mice had significantly fewer M1 and M2 macrophages in the surgically operated joints relative to controls and exhibited decreased osteophyte formation immediately following depletion. Surprisingly, macrophage depletion did not attenuate the severity of OA in obese mice; instead, it induced systemic inflammation and led to a massive infiltration of CD3+ T cells and particularly neutrophils, but not B cells, into the injured joints. Macrophage-depleted mice also demonstrated a markedly increased number of proinflammatory cytokines including granulocyte colony-stimulating factor, interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor in both serum and joint synovial fluid, although the mice showed a trend toward decreased levels of insulin and leptin in serum after macrophage depletion. Our findings indicate that macrophages are vital for modulating homeostasis of immune cells in the setting of obesity and suggest that more targeted approaches of depleting specific macrophage subtypes may be necessary to mitigate inflammation and OA in the setting of obesity. © 2017, American College of Rheumatology.