KSC-2009-1006

NASA Image and Video Library

2009-01-02

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane places the 100-foot fiberglass mast atop the new lightning tower constructed on the pad. The towers are part of the new lightning protection system for the Constellation Program and Ares/Orion launches. Each of the three new lightning towers will be 500 feet tall with the additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Kim Shiflett

Human intestinal mucosal mast cells: expanded population in untreated coeliac disease.

PubMed Central

Strobel, S; Busuttil, A; Ferguson, A

1983-01-01

Previous retrospective studies of intestinal mucosal mast cells in coeliac disease have given divergent results, and we have recently reported that inappropriate methodology could account for these discrepancies. In this prospective study, mucosal mast cell counts were performed in Carnoy fixed, peroral jejunal biopsy specimens from patients with coeliac disease, both untreated and treated with a gluten-free diet; and from controls (mainly irritable bowel syndrome). Mean mucosal mast cell count in 27 control subjects was 146/mm2, SD 29. Significantly higher values were obtained in untreated coeliac disease (mean 243, SD 41, p less than 0.001) returning to the normal range in coeliacs treated with a gluten-free diet with normal jejunal biopsy morphology. In seven patients mucosal mast cell counts were performed in multiple jejunal biopsies, and these showed that mucosal mast cell distribution was not patchy. There was no evidence of degranulation of intestinal mucosal mast cells under the conditions of routine biopsy (overnight fast). An increase in mucosal mast cells in untreated coeliac disease may be one explanation for the high number of IgE positive stained cells in the intestinal mucosa that has been reported by some authors. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6826106

Imaging immune response of skin mast cells in vivo with two-photon microscopy

NASA Astrophysics Data System (ADS)

Li, Chunqiang; Pastila, Riikka K.; Lin, Charles P.

2012-02-01

Intravital multiphoton microscopy has provided insightful information of the dynamic process of immune cells in vivo. However, the use of exogenous labeling agents limits its applications. There is no method to perform functional imaging of mast cells, a population of innate tissue-resident immune cells. Mast cells are widely recognized as the effector cells in allergy. Recently their roles as immunoregulatory cells in certain innate and adaptive immune responses are being actively investigated. Here we report in vivo mouse skin mast cells imaging with two-photon microscopy using endogenous tryptophan as the fluorophore. We studied the following processes. 1) Mast cells degranulation, the first step in the mast cell activation process in which the granules are released into peripheral tissue to trigger downstream reactions. 2) Mast cell reconstitution, a procedure commonly used to study mast cells functioning by comparing the data from wild type mice, mast cell-deficient mice, and mast-cell deficient mice reconstituted with bone marrow-derived mast cells (BMMCs). Imaging the BMMCs engraftment in tissue reveals the mast cells development and the efficiency of BMMCs reconstitution. We observed the reconstitution process for 6 weeks in the ear skin of mast cell-deficient Kit wsh/ w-sh mice by two-photon imaging. Our finding is the first instance of imaging mast cells in vivo with endogenous contrast.

Increased Differentiation of Dermal Mast Cells in Mice Lacking the Mpl Gene

PubMed Central

Ghinassi, Barbara; Zingariello, Maria; Martelli, Fabrizio; Lorenzini, Rodolfo; Vannucchi, Alessandro M.; Rana, Rosa Alba; Nishikawa, Mitsuo; Migliaccio, Giovanni; Mascarenhas, John

2009-01-01

Thrombopoietin interactions with its receptor, Mpl, play an important role in the regulation of hematopoietic stem/progenitor cell proliferation and differentiation. In this study, we report that the mast cell restricted progenitor cells (MCP) and the mast cell precursors in the bone marrow of wild-type mice express Mpl on their surface. Furthermore, targeted deletion of the Mpl gene in mice decreases the number of MCP while increasing the number of mast cell precursors present in the marrow and spleen. It also increases the number of mast cells present in the dermis, in the peritoneal cavity, and in the gut of the mice. In addition, serosal mast cells from Mplnull mice have a distinctive differentiation profile similar to that expressed by wild-type dermal mast cells. These results suggest that not only does ligation of thrombopoietin with the Mpl receptor exert an effect at the mast cell restricted progenitor cell level, but also plays an unexpected yet important role in mast cell maturation. PMID:19025339

Unusual raptor nests around the world

USGS Publications Warehouse

Ellis, D.H.; Craig, T.; Craig, E.; Postupalsky, S.; LaRue, C.T.; Nelson, R.W.; Anderson, D.W.; Henny, C.J.; Watson, J.; Millsap, B.A.; Dawson, J.W.; Cole, K.L.; Martin, E.M.; Margalida, A.; Kung, P.

2009-01-01

From surveys in many countries, we report raptors using unusual nesting materials (e.g., paper money, rags, metal, antlers, and large bones) and unusual nesting situations. For example, we documented nests of Steppe Eagles Aquila nipalensis and Upland Buzzards Buteo hemilasius on the ground beside well-traveled roads, Saker Falcon Falco cherrug eyries in attics and a cistern, and Osprey Pandion haliaetus nests on the masts of boats and on a suspended automobile. Other records include a Golden Eagle A. chrysaetos nest 7.0 m in height, believed to be the tallest nest ever described, and, for the same species, we report nesting in rudimentary nests. Some nest sites are within a few meters of known predators or competitors. These unusual observations may be important in revealing the plasticity of a species' behavioral repertoire. ?? 2009 The Raptor Research Foundation, Inc.

KSC-2009-1584

NASA Image and Video Library

2009-02-13

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, the 100-foot lightning mast has been raised to vertical. It will be lifted and installed on top of the third and final new lightning tower being erected around the pad. The new lightning protection system is being built for the Constellation Program and Ares/Orion launches. Each of the towers is 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Tim Jacobs

KSC-2009-1007

NASA Image and Video Library

2009-01-02

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane places the 100-foot fiberglass mast atop the new lightning tower constructed on the pad. The towers are part of the new lightning protection system for the Constellation Program and Ares/Orion launches. At left of the service structures is another tower under construction. Each of the three new lightning towers will be 500 feet tall with the additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Kim Shiflett

Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

PubMed Central

Akahoshi, Mitsuteru; Song, Chang Ho; Piliponsky, Adrian M.; Metz, Martin; Guzzetta, Andrew; Åbrink, Magnus; Schlenner, Susan M.; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

2011-01-01

Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell–derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell–deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function. PMID:21926462

[Ultrastructural characteristics of mast cells and eosinophils in nasal inverted papilloma].

PubMed

Yokoshima, K; Ohnishi, M; Okuda, M; Okubo, K

1994-12-01

We previously found that an increased number of mast cells and eosinophils accumulated in nasal inverted papilloma and in the nasal mucosa of allergic subjects. Two subtypes of mast cells, i.e., mucosal mast cells and connective tissue mast cells are known to be present in the allergic nasal mucosa. Eosinophils in the allergic nasal mucosa are also heterogeneous. In addition, we demonstrated accumulation of formalin-sensitive mast cells at the tumor site of nasal inverted papilloma. The morphological characteristics and function of mast cells and eosinophils, however, have not yet been identified. The purpose of this study was to determine the ultrastructural characteristics of mast cells and eosinophils in relation to their function in tumor tissue. The results revealed two subtypes of mast cells in nasal inverted papilloma, one distributed mainly in the tumor site, the other mainly in the stromal site. These two subtypes of mast cells had different ultrastructural characteristics. In contrast to stromal mast cells, mast cells in the tumor site were characterized by a smaller cell diameter, fewer specific granules and a higher rate of degranulation. This suggested that they may have played some role in the pathogenesis of the tumor, however, their precise function is still unknown. In comparison with the mast cells in the allergic nasal mucosa, previously reported by Okuda et al, the mast cells in the tumor site were similar to those in the epithelial layer of the allergic nasal mucosa (MMCs), while mast cells in the stromal site resembled those in the lamina propria (CTMCs). There were no marked morphological differences between eosinophils in the tumor site and the stromal site.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow tilt angle measurements using lidar anemometry

NASA Astrophysics Data System (ADS)

Dellwik, Ebba; Mann, Jakob

2010-05-01

A new way of estimating near-surface mean flow tilt angles from ground based Doppler lidar measurements is presented. The results are compared with traditional mast based in-situ sonic anemometry. The tilt angle assessed with the lidar is based on 10 or 30 minute mean values of the velocity field from a conically scanning lidar. In this mode of measurement, the lidar beam is rotated in a circle by a prism with a fixed angle to the vertical at varying focus distances. By fitting a trigonometric function to the scans, the mean vertical velocity can be estimated. Lidar measurements from (1) a fetch-limited beech forest site taken at 48-175m above ground level, (2) a reference site in flat agricultural terrain and (3) a second reference site in very complex terrain are presented. The method to derive flow tilt angles and mean vertical velocities from lidar has several advantages compared to sonic anemometry; there is no flow distortion caused by the instrument itself, there are no temperature effects and the instrument misalignment can be corrected for by comparing tilt estimates at various heights. Contrary to mast-based instruments, the lidar measures the wind field with the exact same alignment error at a multitude of heights. Disadvantages with estimating vertical velocities from a lidar compared to mast-based measurements are slightly increased levels of statistical errors due to limited sampling time, because the sampling is disjunct and a requirement for homogeneous flow. The estimated mean vertical velocity is biased if the flow over the scanned circle is not homogeneous. However, the error on the mean vertical velocity due to flow inhomogeneity can be approximated by a function of the angle of the lidar beam to the vertical, the measurement height and the vertical gradient of the mean vertical velocity, whereas the error due to flow inhomogeneity on the horizontal mean wind speed is independent of the lidar beam angle. For the presented measurements over forest, it is evaluated that the systematic error due to the inhomogeneity of the flow is less than 0.2 degrees. Other possibilities for utilizing lidars for flow tilt angle and mean vertical velocities are discussed.

Human Dermal Mast Cells Contain and Release Tumor Necrosis Factor α, which Induces Endothelial Leukocyte Adhesion Molecule 1

NASA Astrophysics Data System (ADS)

Walsh, Laurence J.; Trinchieri, Giorgio; Waldorf, Heidi A.; Whitaker, Diana; Murphy, George F.

1991-05-01

Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine that mediates endothelial leukocyte interactions by inducing expression of adhesion molecules. In this report, we demonstrate that human dermal mast cells contain sizeable stores of immunoreactive and biologically active TNF-α within granules, which can be released rapidly into the extracellular space upon degranulation. Among normal human dermal cells, mast cells are the predominant cell type that expresses both TNF-α protein and TNF-α mRNA. Moreover, induction of endothelial leukocyte adhesion molecule 1 expression is a direct consequence of release of mast cell-derived TNF-α. These findings establish a role for human mast cells as "gatekeepers" of the dermal microvasculature and indicate that mast cell products other than vasoactive amines influence endothelium in a proinflammatory fashion.

KSC-2009-1561

NASA Image and Video Library

2009-02-12

CAPE CANAVERAL, Fla. – The faint sunrise sky over NASA's Kennedy Space Center casts the newly erected lightning towers on Launch Pad 39B in silhouette. The two towers at left contain the lightning mast on top; the one at right does not. At center are the fixed and rotating service structures that have served the Space Shuttle Program. The new lightning protection system is being built for the Constellation Program and Ares/Orion launches. Each of the towers is 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Jack Pfaller

The role of mast cells in oral squamous cell carcinoma

PubMed Central

Gudiseva, Swetha; Chitturi, Raviteja; Anumula, Vamsikrishna; Poosarla, Chandrashekar; Baddam, Venkat Ramana Reddy

2017-01-01

The mast cells are initial effective lineage in both humoral and adaptive immunity. They are ubiquitous in skin, mucosa, and in function. They contain biologically essential and dynamic mediators in healthy and harmful conditions of tissue. Mast cell malfunctioning could be attributed to various chronic allergic diseases. Considerately, emerging evidence of mast cell involvement in various cancers shows them to have both positive and negative roles in tumour growth. It mostly indulges in tumour progression and metastasis via angiogenesis, extracellular matrix degradation, and mitogenic activity in the tumour microenvironment. The current paper reviewed research papers on mast cells in oral squamous cell carcinoma through the PubMed database from 1980 to the present date. The present paper is an attempt to summarise the research reports on the role of mast cells in oral squamous cell carcinoma. Further to this note, this paper also outlines the role of mast cells in normal physiological processes and tumour biology. PMID:28435394

Patient-Reported Outcome Questionnaire for Systemic Mastocytosis

ClinicalTrials.gov

2017-01-06

Aggressive Systemic Mastocytosis (ASM); SM w Assoc Clonal Hema Non-mast Cell Lineage Disease (SM-AHNMD); Mast Cell Leukemia (MCL); Smoldering Systemic Mastocytosis (SSM); Indolent Systemic Mastocytosis (ISM) ISM Subgroup Fully Recruited

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis.

PubMed

Kempuraj, Duraisamy; Selvakumar, Govindhasamy P; Thangavel, Ramasamy; Ahmed, Mohammad E; Zaheer, Smita; Raikwar, Sudhanshu P; Iyer, Shankar S; Bhagavan, Sachin M; Beladakere-Ramaswamy, Swathi; Zaheer, Asgar

2017-01-01

Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This review focusses on how mast cells in brain injuries, stress, and PTSD may promote the pathogenesis of AD. We suggest that inhibition of mast cells activation and brain cells associated inflammatory pathways in the brain injuries, stress, and PTSD can be explored as a new therapeutic target to delay or prevent the pathogenesis and severity of AD.

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

PubMed Central

Kempuraj, Duraisamy; Selvakumar, Govindhasamy P.; Thangavel, Ramasamy; Ahmed, Mohammad E.; Zaheer, Smita; Raikwar, Sudhanshu P.; Iyer, Shankar S.; Bhagavan, Sachin M.; Beladakere-Ramaswamy, Swathi; Zaheer, Asgar

2017-01-01

Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This review focusses on how mast cells in brain injuries, stress, and PTSD may promote the pathogenesis of AD. We suggest that inhibition of mast cells activation and brain cells associated inflammatory pathways in the brain injuries, stress, and PTSD can be explored as a new therapeutic target to delay or prevent the pathogenesis and severity of AD. PMID:29302258

Fatigue failure and cracking in high mast poles.

DOT National Transportation Integrated Search

2012-03-01

This report presents the findings of a comprehensive research project to investigate the fatigue : cracking and failure of galvanized high mast illumination poles (HMIP). Ultrasonic inspection of : poles throughout the state has revealed the presence...

Giardia lamblia: identification of molecules that contribute to direct mast cell activation.

PubMed

Muñoz-Cruz, Samira; Gomez-García, Argelia; Matadamas-Martínez, Félix; Alvarado-Torres, Juan A; Meza-Cervantez, Patricia; Arriaga-Pizano, Lourdes; Yépez-Mulia, Lilián

2018-06-02

Mast cells play a central role in the early clearance of the intestinal parasite Giardia lamblia. In a previous study, we reported that G. lamblia live trophozoites or trophozoite-derived total soluble extract induced direct activation (IgE-independent) of mast cells and release of IL-6 and TNF-α. To identify the Giardia molecules and the mast cell receptors involved in this activation, trophozoite-derived total soluble proteins separated into three fractions (F1-F3) were evaluated for its ability to activate mast cells in vitro. F2 activated mast cells in a greater extent than F1 and F3. Furthermore, F2 induced the release of IL-6 and TNF-α by mast cells. TLR2 and TLR4 expression increased slightly after mast cell stimulation with either F2 or total soluble extract; however, these receptors were not involved in F2 or total soluble extract-induced proinflammatory cytokine production. Proteins present in F2 as unique and high-intensity bands identified by liquid chromatography coupled with tandem mass spectrometry, include molecules with important biological activities such as enolase and arginine deiminase (ADI). Recombinant ADI and enolase were tested for their ability to activate mast cells, but only ADI induced a significant release of IL-6 and TNF-α. ADI product, citrulline but not ammonium, also induced mast cell release of TNF-α. Interestingly, recombinant ADI still stimulated the secretion of TNF-α by mast cells in a arginine-free medium, although in a lower extend that in the presence of arginine, indicating that either ADI itself can stimulate mast cells or through its metabolic product, citrulline.

The association of mast cells and serotonin in children with chronic abdominal pain of unknown etiology

PubMed Central

2010-01-01

Background Abdominal pain of unknown origin affects up to 20% of school-aged children. Evaluation of children is symptom-based without clear guidelines to investigate molecular mechanisms of abdominal pain. Aberrant molecular mechanisms may increase intestinal permeability leading to interactions between the immune and nervous systems, subclinical inflammation, and visceral pain. This study evaluated the association between interleukin-6 (IL-6), mast cell infiltrates, and serotonin (5-HT) levels in gastrointestinal (GI) biopsies, with perceived abdominal pain in a pediatric cohort. Methods Clinical data and biopsy samples from pediatric patients (n = 48) with chronic abdominal pain, with and without inflammation were included. Formalin-fixed paraffin-embedded GI biopsies were sectioned and immunohistochemistry performed for IL-6 and 5-HT; mast cells were identified with toluidine blue stain. Histological findings were compared to self-reported abdominal pain between groups. Results There was significantly greater IL-6 immunoreactivity in biopsies with confirmed histologic inflammation (p = 0.004). There was a greater number of mast cells per HPF in non-inflammatory biopsies (3.5 ± 2.9) compared to the inflammatory biopsies (2.6 ± 1.8) p = 0.049. The non-inflammatory biopsy group was significantly less likely to respond to standard treatment as evidenced by higher pain reports (p = .018). Mast cells (p = .022) and 5-HT (p = .02) were significantly related to abdominal pain scores. Conclusions A potential association between self-reported abdominal pain, number of mast cells, and 5-HT levels, which may contribute to perceived GI pain in pediatric patients may exist. PMID:20964845

Lin- CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors.

PubMed

Dahlin, Joakim S; Malinovschi, Andrei; Öhrvik, Helena; Sandelin, Martin; Janson, Christer; Alving, Kjell; Hallgren, Jenny

2016-01-28

Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage-negative (Lin(-)) CD34(hi) CD117(int/hi) FcεRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A messenger RNA transcripts were detected by quantitative reverse transcription-polymerase chain reaction. Altogether, we propose that the Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood mast cell progenitors than asthmatics with normal lung function. © 2016 by The American Society of Hematology.

Inhibitory effect of carotenoids on the degranulation of mast cells via suppression of antigen-induced aggregation of high affinity IgE receptors.

PubMed

Sakai, Shota; Sugawara, Tatsuya; Matsubara, Kiminori; Hirata, Takashi

2009-10-09

Carotenoids have been demonstrated to possess antioxidative and anti-inflammatory effects. However, there is no report that the effects of carotenoids on degranulation of mast cell is critical for type I allergy. In this study, we focused on the effect of carotenoids on antigen-induced degranulation of mast cells. Fucoxanthin, astaxanthin, zeaxanthin, and beta-carotene significantly inhibited the antigen-induced release of beta-hexosaminidase in rat basophilic leukemia 2H3 cells and mouse bone marrow-derived mast cells. Those carotenoids also inhibited antigen-induced aggregation of the high affinity IgE receptor (Fc epsilonRI), which is the most upstream of the degranulating signals of mast cells. Furthermore, carotenoids inhibited Fc epsilonRI-mediated intracellular signaling, such as phosphorylation of Lyn kinase and Fyn kinase. It suggests that the inhibitory effect of carotenoids on the degranulation of mast cells were mainly due to suppressing the aggregation of Fc epsilonRI followed by intracellular signaling. In addition, those carotenoids inhibited antigen-induced translocation of Fc epsilonRI to lipid rafts, which are known as platforms of the aggregation of Fc epsilonRI. We assume that carotenoids may modulate the function of lipid rafts and inhibit the translocation of Fc epsilonRI to lipid rafts. This is the first report that focused on the aggregation of Fc epsilonRI to investigate the mechanism of the inhibitory effects on the degranulation of mast cells and evaluated the functional activity of carotenoids associated with lipid rafts.

Inhibitory Effect of Carotenoids on the Degranulation of Mast Cells via Suppression of Antigen-induced Aggregation of High Affinity IgE Receptors*

PubMed Central

Sakai, Shota; Sugawara, Tatsuya; Matsubara, Kiminori; Hirata, Takashi

2009-01-01

Carotenoids have been demonstrated to possess antioxidative and anti-inflammatory effects. However, there is no report that the effects of carotenoids on degranulation of mast cell is critical for type I allergy. In this study, we focused on the effect of carotenoids on antigen-induced degranulation of mast cells. Fucoxanthin, astaxanthin, zeaxanthin, and β-carotene significantly inhibited the antigen-induced release of β-hexosaminidase in rat basophilic leukemia 2H3 cells and mouse bone marrow-derived mast cells. Those carotenoids also inhibited antigen-induced aggregation of the high affinity IgE receptor (FcϵRI), which is the most upstream of the degranulating signals of mast cells. Furthermore, carotenoids inhibited FcϵRI-mediated intracellular signaling, such as phosphorylation of Lyn kinase and Fyn kinase. It suggests that the inhibitory effect of carotenoids on the degranulation of mast cells were mainly due to suppressing the aggregation of FcϵRI followed by intracellular signaling. In addition, those carotenoids inhibited antigen-induced translocation of FcϵRI to lipid rafts, which are known as platforms of the aggregation of FcϵRI. We assume that carotenoids may modulate the function of lipid rafts and inhibit the translocation of FcϵRI to lipid rafts. This is the first report that focused on the aggregation of FcϵRI to investigate the mechanism of the inhibitory effects on the degranulation of mast cells and evaluated the functional activity of carotenoids associated with lipid rafts. PMID:19700409

The transcriptome of the human mast cell leukemia cells HMC-1.2: an approach to identify specific changes in the gene expression profile in KitD816V systemic mastocytosis.

PubMed

Haenisch, B; Herms, S; Molderings, G J

2013-05-01

To circumvent the costly isolation procedure associated with tissue mast cells, human mast cell lines such as HMC-1 are employed in mastocytosis research, but their relation to mutated mast cells in systemic mastocytosis has not been investigated systematically. In the present study, we determined the transcriptome of HMC-1.2 cells and compared the expression data with those reported in the literature for normal human resting lung and tonsillar mast cells as well as leukocytes from peripheral blood and mononuclear cells from bone marrow aspirates of patients with D816 V-positive systemic mastocytosis. Our results suggest that HMC-1.2 cells are an appropriate model for the investigation of this variant of systemic mast cell activation disease. The data confirm previous suggestions that the pathologically increased activity of mast cells in patients with D816 V-positive systemic mastocytosis can be deduced from the detection of mutation-related changes in the gene expression profile in leukocytes from peripheral blood and in mononuclear cells from bone marrow aspirates. Thus, mutation-related changes of the expression profile can serve as surrogates (besides clustering of mast cells, expression of CD25, and increased release of tryptase) for the presence of the mutation D816 V in tyrosine kinase Kit in patients with systemic mastocytosis according to the WHO criteria. Whether this also holds true for systemic mast cell activation disease caused by other mutations in Kit or other mast cell activity-related genes is a subject for future studies.

Interaction of primary mast cells with Borrelia burgdorferi (sensu stricto): role in transmission and dissemination in C57BL/6 mice.

PubMed

Bernard, Quentin; Wang, Zhenping; Di Nardo, Anna; Boulanger, Nathalie

2017-06-27

Borrelia burgdorferi (sensu lato), the causative agent of Lyme borreliosis is a bacterium transmitted by hard ticks, Ixodes spp. Bacteria are injected into the host skin during the tick blood meal with tick saliva. There, Borrelia and saliva interact together with skin cells such as keratinocytes, fibroblasts, mast cells and other specific immune cells before disseminating to target organs. To study the role of mast cells in the transmission of Lyme borreliosis, we isolated mouse primary mast cells from bone marrow and incubated them in the presence of Borrelia burgdorferi (sensu stricto) and tick salivary gland extract. We further analyzed their potential role in vivo, in a mouse model of deficient in mast cells (Kit wsh-/- mice). To our knowledge, we report here for the first time the bacteria ability to induce the inflammatory response of mouse primary mast cells. We show that OspC, a major surface lipoprotein involved in the early transmission of Borrelia, induces the degranulation of primary mast cells but has a limited effect on the overall inflammatory response of these cells. In contrast, whole bacteria have an opposite effect. We also show that mast cell activation is significantly inhibited by tick salivary gland extract. Finally, we demonstrate that mast cells are likely not the only host cells involved in the early transmission and dissemination of Borrelia since the use of mast cell deficient Kit wsh-/- mice shows a limited impact on these two processes in the context of this mouse genetic background. The absence of mast cells did not change the replication rate of Borrelia in the skin. However, in the absence of mast cells, Borrelia dissemination to the joints was faster. Mast cells do not control skin bacterial proliferation during primary infection and the establishment of the primary infection, as shown in the C57BL/6 mouse model studied. Nevertheless, the Borrelia induced cytotokine modulation on mast cells might be involved in long term and/or repeated infections and protect from Lyme borreliosis due to the development of a hypersensitivity to tick saliva.

Development and Initial Review of the Mark II Navy 44 Sail Training Craft

DTIC Science & Technology

2009-03-01

intensive training environment) • Offshore capability for trips to Bermuda with a semi-skilled crew of ten • Favorable treatment under existing rating... triangle and headsails • Existing systems by type, to be updated as directed Features to be improved: • Construction materials, scantlings and...consistent with the MK I’s. The mast height, standing rigging and fore triangle base had to be identical between the MK I and MK II. However, PYD wanted

Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms.

PubMed

Johnson, Monica; Alsaleh, Nasser; Mendoza, Ryan P; Persaud, Indushekhar; Bauer, Alison K; Saba, Laura; Brown, Jared M

2018-01-01

Mast cells represent a crucial cell type in host defense; however, maladaptive responses are contributing factors in the pathogenesis of allergic diseases. Previous work in our laboratory has shown that exposure to silver nanoparticles (AgNPs) results in mast cell degranulation via a non-immunoglobulin E (IgE) mechanism. In this study, we utilized a systems biology approach to identify novel genetic factors playing a role in AgNP-induced mast cell degranulation compared to the classical activation by antigen-mediated FcεRI crosslinking. Mast cell degranulation was assessed in bone marrow-derived mast cells isolated from 23 strains of mice following exposure to AgNPs or FcεRI crosslinking with dinitrophenyl (DNP). Utilizing strain-dependent mast cell degranulation, an association mapping study identified 3 chromosomal regions that were significantly associated with mast cell degranulation by AgNP and one non-overlapping region associated with DNP-mediated degranulation. Two of the AgNP-associated regions correspond to genes previously reported to be associated with allergic disorders (Trac2 on chromosome 1 and Traf6 on chromosome 2) and an uncharacterized gene identified on chromosome 1 (Fam126b). In conjunction, RNA-sequencing performed on mast cells from the high and low responder strains revealed 3754 and 34 differentially expressed genes that were unique to DNP and AgNP exposures, respectively. Select candidate genes include Ptger4, a gene encoding a G-protein coupled receptor in addition to a multifunctional adaptor protein, Txnip, that may be driving mast cell degranulation by AgNP. Taken together, we identified novel genes that have not been previously shown to play a role in nanoparticle-mediated mast cell activation. With further functional evaluation in the future, these genes may be potential therapeutic targets in the treatment of non-IgE mediated mast cell-linked disorders.

Unusual Electric Burns Caused by Communication Disc Contact with a High-voltage Electric Transmission Cable: a Potential Occupational Hazard

PubMed Central

Fadeyibi, I.O.; Izegbu, M.C.; Benebo, A.S.; Ademuluyi, S.A.

2007-01-01

Summary The case reported is that of a communications technician admitted to hospital with 38% burns sustained while climbing a communications mast. The mast was erected less than 3 metres from a 33 kv electric transmission cable. His condition is described, as also the treatment he received until his discharge three months later. In the absence of guidelines regarding the erection of such masts, a number of recommendations are made. PMID:21991082

Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP).

PubMed

Brennan, Tracy A; Lindborg, Carter M; Bergbauer, Christian R; Wang, Haitao; Kaplan, Frederick S; Pignolo, Robert J

2018-04-01

Episodic flare-ups of fibrodysplasia ossificans progressiva (FOP) are characterized clinically by severe, often posttraumatic, connective tissue swelling and intramuscular edema, followed histologically by an intense and highly angiogenic fibroproliferative reaction. This early inflammatory and angiogenic fibroproliferative response is accompanied by the presence of abundant mast cells far in excess of other reported myopathies. Using an injury-induced, constitutively-active transgenic mouse model of FOP we show that mast cell inhibition by cromolyn, but not aprepitant, results in a dramatic reduction of heterotopic ossification. Cromolyn, but not aprepitant, significantly decreases the total number of mast cells in FOP lesions. Furthermore, cromolyn specifically diminishes the number of degranulating and resting degranulated mast cells in pre-osseous lesions. This work demonstrates that consideration of FOP as a type of localized mastocytosis may offer new therapeutic interventions for treatment of this devastating condition. Copyright © 2017 Elsevier Inc. All rights reserved.

Zinc Oxide Nanoparticles Demoted MDM2 Expression to Suppress TSLP-Induced Mast Cell Proliferation.

PubMed

Kim, Min-Ho; Jeong, Hyun-Ja

2016-03-01

Activation of murine double minute 2 (MDM2) through thymic stromal lymphopoietin (TSLP)-induced signal transducers and activators of transcription (STAT6) phosphorylation plays a critical role in proliferation and survival of mast cells. Previously, we reported that zinc oxide nanoparticles (ZnO-NP) effectively decrease the mast cell-mediated allergic inflammatory reactions. Here, we evaluated the effect of ZnO-NP on TSLP-induced proliferation of mast cells. ZnO-NP significantly reduced the number of BrdU-incorporating mast cells increased by TSLP. ZnO-NP decreased the expression of MDM2 through the blockade of STAT6 phosphorylation. TSLP increased the production and mRNA expression of interleukin-13 (a growth factor of mast cells), its increase was significantly decreased by ZnO-NP (10 μg/mL). ZnO-NP induced the down-regulation of Bcl2 (an anti-apoptotic factor) and up-regulation of Bax (an apoptotic factor) through the stabilization of p53 protein. However, ZnO-NP has no effect on caspase-3 activation, cytochrome c release into cytosol, and apoptosis-inducing factor translocation into nucleus in TSLP-stimulated cells. The results of the present study demonstrated that ZnO-NP inhibited the proliferation of mast cells through the regulation of MDM2 and p53 protein levels. These finding suggest that ZnO-NP could be improved mast cell-mediated various diseases.

Mast cells contribute to the mucosal adjuvant effect of CTA1-DD after IgG-complex formation.

PubMed

Fang, Yu; Larsson, Lisa; Mattsson, Johan; Lycke, Nils; Xiang, Zou

2010-09-01

Mast cell activation is one of the most dramatic immune-mediated responses the body can encounter. In the worst scenario (i.e., anaphylaxis), this response is fatal. However, the importance of mast cells as initiators and effectors of both innate and adaptive immunity in healthy individuals has recently been appreciated. It was reported that mast cell activation can be used as an adjuvant to promote Ag-specific humoral immune responses upon vaccination. In this study, we have used a clinically relevant mucosal adjuvant, cholera toxin A1 subunit (CTA1)-DD, which is a fusion protein composed of CTA1, the ADP-ribosylating part of cholera toxin, and DD, two Ig-binding domains derived from Staphylococcus aureus protein A. CTA1-DD in combination with polyclonal IgG induced degranulation and production of TNF-alpha from mouse mast cells. Furthermore, CTA1-DD and polyclonal IgG complex induced mast cell degranulation in mouse skin tissue and nasal mucosa. We also found that intranasal immunization with hapten (4-hydroxy-3-nitrophenyl) acetyl (NP) coupled to chicken gammaglobulin admixed with CTA1-DD complexed with polyclonal IgG greatly enhanced serum IgG anti-NP Ab responses and stimulated higher numbers of NP-specific plasma cells in the bone marrow as compared with that observed in mice immunized with NP-chicken gammaglobulin with CTA1-DD alone. This CTA1-DD/IgG complex-mediated enhancement was mast cell dependent because it was absent in mast cell-deficient Kit(W-sh/W-sh) mice. In conclusion, our data suggest that a clinically relevant adjuvant, CTA1-DD, exerts additional augmenting effects through activation of mucosal mast cells, clearly demonstrating that mast cells could be further exploited for improving the efficacy of mucosal vaccines.

Upregulated expression of substance P (SP) and NK1R in eczema and SP-induced mast cell accumulation.

PubMed

Zhan, Mengmeng; Zheng, Wenjiao; Jiang, Qijun; Zhao, Zuotao; Wang, Zhiyun; Wang, Junling; Zhang, Huiyun; He, Shaoheng

2017-08-01

Substance P (SP) was reported to be associated with eczema and acts as a potent skin mast cell secretagogue. However, little is known of its expression in inflammatory cells in eczema and its ability in induction of mast cell accumulation. In the present study, we investigated expression of SP and neurokinin-1 receptor (NK1R) on peripheral blood leukocytes and mast cells from patients with eczema and influence of SP on mast cell accumulation by using flow cytometry analysis, trans-epithelial cell migration assay and mouse peritoneal model. The results showed that plasma SP and IL-17A levels in eczema patients were higher than that in healthy control subject. The percentages of SP+ and NK1R+ expression populations of monocytes, helper T cells, natural killer T cells and basophils in peripheral blood of eczema patients were markedly elevated. It was observed that not only absolute number of mast cells but also SP+ and NK1R+ mast cells are enhanced in the lesion skin of eczema. SP showed a potent chemoattractant action on mast cells as assessed by a mouse peritoneal model and a trans-endothelium cell migration assay. SP-induced mast cell accumulation appears a CD18/CD11a complex, L-selectin and ICAM-1-dependent event which can be blocked by a NK-1R antagonist RP67580. In conclusion, elevated expression of SP in patients with eczema and the ability of SP in induction of mast cell accumulation indicate strongly that SP is a potent proinflammatory mediator, which contributes to the pathogenesis of eczema. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of eczema.

Type 1 diabetes in NOD mice unaffected by mast cell deficiency.

PubMed

Gutierrez, Dario A; Fu, Wenxian; Schonefeldt, Susann; Feyerabend, Thorsten B; Ortiz-Lopez, Adriana; Lampi, Yulia; Liston, Adrian; Mathis, Diane; Rodewald, Hans-Reimer

2014-11-01

Mast cells have been invoked as important players in immune responses associated with autoimmune diseases. Based on in vitro studies, or in vivo through the use of Kit mutant mice, mast cells have been suggested to play immunological roles in direct antigen presentation to both CD4(+) and CD8(+) T cells, in the regulation of T-cell and dendritic cell migration to lymph nodes, and in Th1 versus Th2 polarization, all of which could significantly impact the immune response against self-antigens in autoimmune disease, including type 1 diabetes (T1D). Until now, the role of mast cells in the onset and incidence of T1D has only been indirectly tested through the use of low-specificity mast cell inhibitors and activators, and published studies reported contrasting results. Our three laboratories have generated independently two strains of mast cell-deficient nonobese diabetic (NOD) mice, NOD.Cpa3(Cre/+) (Heidelberg) and NOD.Kit(W-sh/W-sh) (Leuven and Boston), to address the effects of mast cell deficiency on the development of T1D in the NOD strain. Our collective data demonstrate that both incidence and progression of T1D in NOD mice are independent of mast cells. Moreover, analysis of pancreatic lymph node cells indicated that lack of mast cells has no discernible effect on the autoimmune response, which involves both innate and adaptive immune components. Our results demonstrate that mast cells are not involved in T1D in the NOD strain, making their role in this process nonessential and excluding them as potential therapeutic targets. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Prototype crawling robotics system for remote visual inspection of high-mast light poles.

DOT National Transportation Integrated Search

1997-01-01

This report presents the results of a project to develop a crawling robotics system for the remote visual inspection of high-mast light poles in Virginia. The first priority of this study was to develop a simple robotics application that would reduce...

Mycobacterium tuberculosis Catalase Inhibits the Formation of Mast Cell Extracellular Traps

PubMed Central

Campillo-Navarro, Marcia; Leyva-Paredes, Kahiry; Donis-Maturano, Luis; Rodríguez-López, Gloria M.; Soria-Castro, Rodolfo; García-Pérez, Blanca Estela; Puebla-Osorio, Nahum; Ullrich, Stephen E.; Luna-Herrera, Julieta; Flores-Romo, Leopoldo; Sumano-López, Héctor; Pérez-Tapia, Sonia M.; Estrada-Parra, Sergio; Estrada-García, Iris; Chacón-Salinas, Rommel

2018-01-01

Tuberculosis is one of the leading causes of human morbidity and mortality. Mycobacterium tuberculosis (Mtb) employs different strategies to evade and counterattack immune responses persisting for years. Mast cells are crucial during innate immune responses and help clear infections via inflammation or by direct antibacterial activity through extracellular traps (MCETs). Whether Mtb induce MCETs production is unknown. In this study, we report that viable Mtb did not induce DNA release by mast cells, but heat-killed Mtb (HK-Mtb) did. DNA released by mast cells after stimulation with HK-Mtb was complexed with histone and tryptase. MCETs induced with PMA and HK-Mtb were unable to kill live Mtb bacilli. Mast cells stimulated with HK-Mtb induced hydrogen peroxide production, whereas cells stimulated with viable Mtb did not. Moreover, MCETs induction by HK-Mtb was dependent of NADPH oxidase activity, because its blockade resulted in a diminished DNA release by mast cells. Interestingly, catalase-deficient Mtb induced a significant production of hydrogen peroxide and DNA release by mast cells, indicating that catalase produced by Mtb prevents MCETs release by degrading hydrogen peroxide. Our findings show a new strategy employed by Mtb to overcome the immune response through inhibiting MCETs formation, which could be relevant during early stages of infection. PMID:29892297

Mycobacterium tuberculosis Catalase Inhibits the Formation of Mast Cell Extracellular Traps.

PubMed

Campillo-Navarro, Marcia; Leyva-Paredes, Kahiry; Donis-Maturano, Luis; Rodríguez-López, Gloria M; Soria-Castro, Rodolfo; García-Pérez, Blanca Estela; Puebla-Osorio, Nahum; Ullrich, Stephen E; Luna-Herrera, Julieta; Flores-Romo, Leopoldo; Sumano-López, Héctor; Pérez-Tapia, Sonia M; Estrada-Parra, Sergio; Estrada-García, Iris; Chacón-Salinas, Rommel

2018-01-01

Tuberculosis is one of the leading causes of human morbidity and mortality. Mycobacterium tuberculosis (Mtb) employs different strategies to evade and counterattack immune responses persisting for years. Mast cells are crucial during innate immune responses and help clear infections via inflammation or by direct antibacterial activity through extracellular traps (MCETs). Whether Mtb induce MCETs production is unknown. In this study, we report that viable Mtb did not induce DNA release by mast cells, but heat-killed Mtb (HK-Mtb) did. DNA released by mast cells after stimulation with HK-Mtb was complexed with histone and tryptase. MCETs induced with PMA and HK-Mtb were unable to kill live Mtb bacilli. Mast cells stimulated with HK-Mtb induced hydrogen peroxide production, whereas cells stimulated with viable Mtb did not. Moreover, MCETs induction by HK-Mtb was dependent of NADPH oxidase activity, because its blockade resulted in a diminished DNA release by mast cells. Interestingly, catalase-deficient Mtb induced a significant production of hydrogen peroxide and DNA release by mast cells, indicating that catalase produced by Mtb prevents MCETs release by degrading hydrogen peroxide. Our findings show a new strategy employed by Mtb to overcome the immune response through inhibiting MCETs formation, which could be relevant during early stages of infection.

The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization.

PubMed

Fang, Y; Zhang, T; Lidell, L; Xu, X; Lycke, N; Xiang, Z

2013-11-01

We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.

Innate defense regulator IDR-1018 activates human mast cells through G protein-, phospholipase C-, MAPK- and NF-ĸB-sensitive pathways.

PubMed

Yanashima, Kensuke; Chieosilapatham, Panjit; Yoshimoto, Eri; Okumura, Ko; Ogawa, Hideoki; Niyonsaba, François

2017-08-01

Host defense (antimicrobial) peptides not only display antimicrobial activities against numerous pathogens but also exert a broader spectrum of immune-modulating functions. Innate defense regulators (IDRs) are a class of host defense peptides synthetically developed from natural or endogenous cationic host defense peptides. Of the IDRs developed to date, IDR-1018 is more efficient not only in killing bacteria but also in regulating the various functions of macrophages and neutrophils and accelerating the wound healing process. Because mast cells intimately participate in wound healing and a number of host defense peptides involved in wound healing are also known to activate mast cells, this study aimed to investigate the effects of IDR-1018 on mast cell activation. Here, we showed that IDR-1018 induced the degranulation of LAD2 human mast cells and caused their production of leukotrienes, prostaglandins and various cytokines and chemokines, including granulocyte-macrophage colony-stimulating factor, interleukin-8, monocyte chemoattractant protein-1 and -3, macrophage-inflammatory protein-1α and -1β, and tumor necrosis factor-α. Furthermore, IDR-1018 increased intracellular calcium mobilization and induced mast cell chemotaxis. The mast cell activation was markedly suppressed by pertussis toxin, U-73122, U0126, SB203580, JNK inhibitor II, and NF-κB activation inhibitor II, suggesting the involvement of G-protein, phospholipase C, ERK, p38, JNK and NF-κB pathways, respectively, in IDR-1018-induced mast cell activation. Notably, we confirmed that IDR-1018 caused the phosphorylation of MAPKs and IκB. Altogether, the current study suggests a novel immunomodulatory role of IDR-1018 through its ability to recruit and activate human mast cells at the sites of inflammation and wounds. We report that IDR-1018 stimulates various functions of human mast cells. IDR-1018-induced mast cell activation is mediated through G protein, PLC, MAPK and NF-κB pathways. IDR-1018 will be a useful therapeutic agent for wound healing.

Anti-allergic activity of 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) via attenuation of IgE-mediated mast cell activation and inhibition of passive systemic anaphylaxis

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

Tan, Ji Wei; Israf, Daud Ahmad; Harith, Hanis Haze

tHGA, a geranyl acetophenone compound originally isolated from a local shrub called Melicope ptelefolia, has been previously reported to prevent ovalbumin-induced allergic airway inflammation in a murine model of allergic asthma by targeting cysteinyl leukotriene synthesis. Mast cells are immune effector cells involved in the pathogenesis of allergic diseases including asthma by releasing cysteinyl leukotrienes. The anti-asthmatic properties of tHGA could be attributed to its inhibitory effect on mast cell degranulation. As mast cell degranulation is an important event in allergic responses, this study aimed to investigate the anti-allergic effects of tHGA in cellular and animal models of IgE-mediated mastmore » cell degranulation. For in vitro model of IgE-mediated mast cell degranulation, DNP-IgE-sensitized RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA to induce degranulation. For IgE-mediated passive systemic anaphylaxis, Sprague Dawley rats were sensitized by intraperitoneal injection of DNP-IgE before challenged with DNP-BSA. Both in vitro and in vivo models showed that tHGA significantly inhibited the release of preformed mediators (β-hexosaminidase and histamine) as well as de novo mediators (interleukin-4, tumour necrosis factor-α, prostaglandin D{sub 2} and leukotriene C{sub 4}). Pre-treatment of tHGA also prevented IgE-challenged RBL-2H3 cells and peritoneal mast cells from undergoing morphological changes associated with mast cell degranulation. These findings indicate that tHGA possesses potent anti-allergic activity via attenuation of IgE-mediated mast cell degranulation and inhibition of IgE-mediated passive systemic anaphylaxis. Thus, tHGA may have the potential to be developed as a mast cell stabilizer for the treatment of allergic diseases in the future. - Highlights: • The in vitro and in vivo mast cell stabilizing effects of tHGA were examined. • tHGA counteracts the plasma membrane deformation in degranulating mast cells. • tHGA attenuates preformed and de novo mediators released by degranulating mast cells. • tHGA prevents in vivo mast cell activation and passive systemic anaphylaxis in rats. • tHGA could be a potential mast cell stabilizer for the treatment of allergic diseases.« less

[Ala12]MCD peptide: a lead peptide to inhibitors of immunoglobulin E binding to mast cell receptors.

PubMed

Buku, A; Condie, B A; Price, J A; Mezei, M

2005-09-01

An effort was made to discover mast cell degranulating (MCD) peptide analogs that bind with high affinity to mast cell receptors without triggering secretion of histamine or other mediators of the allergic reaction initiated by immunoglobulin E (IgE) after mast cell activation. Such compounds could serve as inhibitors of IgE binding to mast cell receptors. An alanine scan of MCD peptide reported previously showed that the analog [Ala12]MCD was 120-fold less potent in histamine-releasing activity and fivefold more potent in binding affinity to mast cell receptors than the parent MCD peptide. Because this analog showed marginal intrinsic activity and good binding affinity it was subsequently tested in the present study as an IgE inhibitor. In contrast to MCD peptide, [Ala12]MCD showed a 50% inhibition of IgE binding to the Fc epsilon RI alpha mast cell receptor by using rat basophilic leukemia (RBL-2H3) mast cells and fluorescence polarization. Furthermore, in a beta-hexosaminidase secretory assay, the peptide also showed a 50% inhibition of the secretion of this enzyme caused by IgE. An attempt was made to relate structural changes and biologic differences between the [Ala12]MCD analog and the parent MCD peptide. The present results show that [Ala12]MCD may provide a base for designing agents to prevent IgE/Fc epsilon RI alpha interactions and, consequently, allergic conditions.

Analyses of changes on skin by aging.

PubMed

Kazanci, A; Kurus, M; Atasever, A

2017-02-01

This study aimed to evaluate the histological changes occurring in rat skin with increasing age, starting from the intrauterine period. Thirty-two healthy female Sprague-Dawley rats were evaluated in four groups: group 1 - intrauterine day 19, group 2 - postpartum day 21, group 3 - postpartum day 60, and group 4 - postpartum month 19. Skin samples from the back, abdomen, head, and upper and lower limbs were obtained from each subject under anesthesia. Tissue specimens were evaluated statistically and morphologically for the thicknesses of the epidermis, dermis, and basement membrane; the number, height, and width of dermal papillae; and the mast cell and pilosebaceous counts per group. The changes in collagen/elastic fibers and glycosaminoglycans were also assessed. Epidermal thickness was the highest in the intrauterine group; it decreased in the postpartum period and increased again in the aged group. Basal membrane thickness increased steadily with age. The number, height, and width of dermal papillae and dermal thickness increased up to day 60 after birth although these decreased in the aged group. Mast cell count also reached the maximum in the intrauterine group and gradually decreased with age. Pilosebaceous units of the dermis were fewer in intrauterine specimens; they showed an increase during the postpartum period and a decrease in the aged group. Skin specimens obtained from rats showed striking differences between the intrauterine and postpartum groups. Moreover, the postpartum group showed considerable intra-group differences. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

3D turbulence measurements using three intersecting Doppler LiDAR beams: validation against sonic anemometry

NASA Astrophysics Data System (ADS)

Carbajo Fuertes, Fernando; Valerio Iungo, Giacomo; Porté-Agel, Fernando

2013-04-01

Nowadays communities of researchers and industry in the wind engineering and meteorology sectors demand extensive and accurate measurements of atmospheric boundary layer turbulence for a better understanding of its role in a wide range of onshore and offshore applications: wind resource evaluation, wind turbine wakes, meteorology forecast, pollution and urban climate studies, etc. Atmospheric turbulence has been traditionally investigated through sonic anemometers installed on meteorological masts. However, the setup and maintenance of instrumented masts is generally very costly and the available location for the measurements is limited by the fixed position and height of the facility. In order to overcome the above-mentioned shortcomings, a measurement technique is proposed, based on the reconstruction of the three-dimensional velocity vector from simultaneous measurements of three intersecting Doppler wind LiDARs. This measuring technique presents the main advantage of being able to measure the wind velocity at any point in space inside a very large volume, which can be set and optimized for each test. Furthermore, it is very flexible regarding its transportation, installation and operation in any type of terrain. On the other hand, LiDAR measurements are strongly affected by the aerosol concentration in the air, precipitation, and the spatial and temporal resolution is poorer than that of a sonic anemometer. All this makes the comparison between these two kinds of measurements a complex task. The accuracy of the technique has been assessed by this study against sonic anemometer measurements carried out at different heights on the KNMI's meteorological mast at Cabauw's experimental site for atmospheric research (CESAR) in the Netherlands. An early uncertainty analysis shows that one of the most important parameters to be taken into account is the relative angles between the intersecting laser beams, i.e., the position of each LiDAR on the terrain and their elevation and azimuth angles. Following this analysis, different LiDAR layouts have been tested, e.g., one vertical beam and the other two almost horizontal, all three equidistant with the same elevation angle, etc. Preliminary results show different degrees of agreement between the proposed technique and the sonic anemometers depending on the LiDARs layout, which is in agreement with the uncertainty analysis carried out. The best configurations show a good agreement for the three components of the velocity and turbulence spectra, thus proving the ability of the technique to measure accurately atmospheric turbulence, consolidating it as a very interesting alternative to meteorological masts for many different applications.

Density-dependent dynamics of a dominant rain forest tree change with juvenile stage and time of masting.

PubMed

Norghauer, Julian M; Newbery, David M

2016-05-01

Although negative density dependence (NDD) can facilitate tree species coexistence in forests, the underlying mechanisms can differ, and rarely are the dynamics of seedlings and saplings studied together. Herein we present and discuss a novel mechanism based on our investigation of NDD predictions for the large, grove-forming ectomycorrhizal mast fruiting tree, Microberlinia bisulcata (Caesalpiniaceae), in an 82.5-ha plot at Korup, Cameroon. We tested whether juvenile density, size, growth and survival decreases with increasing conspecific adult basal area for 3245 'new' seedlings and 540 'old' seedlings (< 75-cm tall) during an approximately 4-year study period (2008-2012) and for 234 'saplings' (≥ 75-cm tall) during an approximately 6-year study period (2008-2014). We found that the respective densities of new seedlings, old seedlings and saplings were positively, not and negatively related to increasing BA. Maximum leaf numbers and heights of old seedlings were negatively correlated with increasing basal areas, as were sapling heights and stem diameters. Whereas survivorship of new seedlings decreased by more than one-half with increasing basal area over its range in 2010-2012, that of old seedlings decreased by almost two-thirds, but only in 2008-2010, and was generally unrelated to conspecific seedling density. In 2010-2012 relative growth rates in new seedlings' heights decreased with increasing basal area, as well as with increasing seedling density, together with increasing leaf numbers, whereas old seedlings' growth was unrelated to either conspecific density or basal area. Saplings of below-average height had reduced survivorship with increasing basal area (probability decreasing from approx. 0.4 to 0.05 over the basal area range tested), but only sapling growth in terms of leaf numbers decreased with increasing basal area. These static and dynamic results indicate that NDD is operating within this system, possibly stabilizing the M. bisulcata population. However, these NDD patterns are unlikely to be caused by symmetric competition or by consumers. Instead, an alternative mechanism for conspecific adult-juvenile negative feedback is proposed, one which involves the interaction between tree phenology and ectomycorrhizal linkages.

Characterization of a mast cell line that lacks the extracellular domain of membrane c-kit.

PubMed

Mekori, Y A; Oh, C K; Dastych, J; Goff, J P; Adachi, S; Bianchine, P J; Worobec, A; Semere, T; Pierce, J H; Metcalfe, D D

1997-04-01

Expression of the c-kit proto-oncogene receptor on mast cells is essential for their normal proliferation and maturation as well as for several biological responses such as chemotaxis and attachment. In the present study we report that the interleukin-3 (IL-3)-dependent mast cell line CFTL-15 lacks the extracellular domain of the c-kit receptor. This observation was made after noting that the c-kit ligand stem cell factor (SCF) could not prevent IL-3 deprivation-induced mast cell apoptosis and that CFTL-15 cells did not proliferate in response to SCF. Flow cytometric analysis employing monoclonal anti-c-kit antibodies, and immunogold labelling with analysis by electron microscopy, subsequently showed a diminished expression of c-kit on CFTL-15 cells. There was no identifiable message for the extracellular domain of c-kit in these cells, as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). These previously unrecognized properties of the CFTL-15 mast cell line allowed the examination of other biological consequences of the lack of c-kit on mast cells. Analysing the ability of these cells to adhere to surface-bound fibronectin, it was found that addition of SCF did not increase their adhesion to this substrate, in opposition to what is reported with other mast cells. Similarly, CFTL-15 mast cells did not adhere to fibroblasts, which is known to require c-kit expression. Also, there was no protein tyrosine phosphorylation in these cells in response to SCF. CFTL-15 cells underwent apoptosis on removal of IL-3 coincident with a decrease in endogenous Bcl-2 mRNA. Overexpression of Bcl-2 cDNA prolonged survival of Bcl-2-transfected CFTL-15 cells upon withdrawal of IL-3. Thus, the CFTL-15 cell line that lacks surface c-kit is not able to proliferate in response to SCF, undergoes apoptosis in the presence of SCF, and does not adhere to fibroblasts. These results confirm earlier studies on the functional consequences of c-kit and provide a novel experimental model for further investigation.

Characterization of a mast cell line that lacks the extracellular domain of membrane c-kit.

PubMed Central

Mekori, Y A; Oh, C K; Dastych, J; Goff, J P; Adachi, S; Bianchine, P J; Worobec, A; Semere, T; Pierce, J H; Metcalfe, D D

1997-01-01

Expression of the c-kit proto-oncogene receptor on mast cells is essential for their normal proliferation and maturation as well as for several biological responses such as chemotaxis and attachment. In the present study we report that the interleukin-3 (IL-3)-dependent mast cell line CFTL-15 lacks the extracellular domain of the c-kit receptor. This observation was made after noting that the c-kit ligand stem cell factor (SCF) could not prevent IL-3 deprivation-induced mast cell apoptosis and that CFTL-15 cells did not proliferate in response to SCF. Flow cytometric analysis employing monoclonal anti-c-kit antibodies, and immunogold labelling with analysis by electron microscopy, subsequently showed a diminished expression of c-kit on CFTL-15 cells. There was no identifiable message for the extracellular domain of c-kit in these cells, as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). These previously unrecognized properties of the CFTL-15 mast cell line allowed the examination of other biological consequences of the lack of c-kit on mast cells. Analysing the ability of these cells to adhere to surface-bound fibronectin, it was found that addition of SCF did not increase their adhesion to this substrate, in opposition to what is reported with other mast cells. Similarly, CFTL-15 mast cells did not adhere to fibroblasts, which is known to require c-kit expression. Also, there was no protein tyrosine phosphorylation in these cells in response to SCF. CFTL-15 cells underwent apoptosis on removal of IL-3 coincident with a decrease in endogenous Bcl-2 mRNA. Overexpression of Bcl-2 cDNA prolonged survival of Bcl-2-transfected CFTL-15 cells upon withdrawal of IL-3. Thus, the CFTL-15 cell line that lacks surface c-kit is not able to proliferate in response to SCF, undergoes apoptosis in the presence of SCF, and does not adhere to fibroblasts. These results confirm earlier studies on the functional consequences of c-kit and provide a novel experimental model for further investigation. Images Figure 4 Figure 6 Figure 7 Figure 8 PMID:9176104

Changes in numbers and types of mast cell colony-forming cells in the peritoneal cavity of mice after injection of distilled water: evidence that mast cells suppress differentiation of bone marrow-derived precursors

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

Kanakura, Y.; Kuriu, A.; Waki, N.

Two different types of cells in the peritoneal cavity of mice produce mast cell colonies in methylcellulose. Large mast cell colonies are produced by bone marrow-derived precursors resembling lymphoid cells by light microscopy (L-CFU-Mast), whereas medium and small mast cell colonies are produced by morphologically identifiable mast cells (M-CFU-Mast and S-CFU-Mast, respectively). In the present study we eradicated peritoneal mast cells by intraperitoneal (IP) injection of distilled water. The regeneration process was investigated to clarify the relationship between L-CFU-Mast, M-CFU-Mast, and S-CFU-Mast. After injection of distilled water, M-CFU-Mast and S-CFU-Mast disappeared, but L-CFU-Mast increased, and then M-CFU-Mast and S-CFU-Mast appeared,more » suggesting the presence of a hierarchic relationship. When purified peritoneal mast cells were injected two days after the water injection, the L-CFU-Mast did not increase. In the peritoneal cavity of WBB6F1-+/+ mice that had been lethally irradiated and rescued by bone marrow cells of C57BL/6-bgJ/bgJ (beige, Chediak-Higashi syndrome) mice, L-CFU-Mast were of bgJ/bgJ type, but M-CFU-Mast and S-CFU-Mast were of +/+ type. The injection of distilled water to the radiation chimeras resulted in the development of bgJ/bgJ-type M-CFU-Mast and then S-CFU-Mast. The presence of mast cells appeared to suppress the recruitment of L-CFU-Mast from the bloodstream and to inhibit the differentiation of L-CFU-Mast to M-CFU-Mast.« less

Long-term monitoring of fleshy fruit and hard mast production and seasonal bird distribution at the Savannah River Site, South Carolina.

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

Greenberg, Cathryn, H.; Levey, Douglas J.

2009-06-15

A final report of Fruit and hard mast production in five habitat types at SRS with a comparison of fruit consumption by fledgling versus adult birds at SRS and Relative importance of fruit, seeds, and insects in the diets of overwintering birds at SRS.

Brief Report: "Allergic Symptoms" in Children with Autism Spectrum Disorders. More than Meets the Eye?

ERIC Educational Resources Information Center

Angelidou, Asimenia; Alysandratos, Konstantinos-Dionysios; Asadi, Shahrzad; Zhang, Bodi; Francis, Konstantinos; Vasiadi, Magdalini; Kalogeromitros, Dimitrios; Theoharides, Theoharis C.

2011-01-01

Many children with Autism Spectrum Disorders (ASD) have either family and/or personal history of "allergic symptomatology", often in the absence of positive skin or RAST tests. These symptoms may suggest mast cell activation by non-allergic triggers. Moreover, children with mastocytosis or mast cell activation syndrome (MCAS), a spectrum of rare…

KSC-2009-1334

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane begins lifting a 100-foot fiberglass lightning mast to place it on top of one of the 500-foot towers being constructed for the Constellation Program and Ares/Orion launches. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009.

KSC-2009-1333

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane begins lifting a 100-foot fiberglass lightning mast to place it on top of one of the 500-foot towers being constructed for the Constellation Program and Ares/Orion launches. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009.

KSC-2009-1331

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane lifts a 100-foot fiberglass lightning mast that will be placed on top of one of the 500-foot towers being constructed for the Constellation Program and Ares/Orion launches. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009.

KSC-2009-1335

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane lifts a 100-foot fiberglass lightning mast alongside the 500-foot tower where it will be installed. The tower is one of three being constructed for the Constellation Program and Ares/Orion launches. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009.

KSC-2009-1338

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane places a 100-foot fiberglass lightning mast on top of the 500-foot tower. The tower is one of three being constructed for the Constellation Program and Ares/Orion launches. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-1332

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane holds a 100-foot fiberglass lightning mast that will be placed on top of one of the 500-foot towers being constructed for the Constellation Program and Ares/Orion launches. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009.

KSC-2009-1337

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane places a 100-foot fiberglass lightning mast on top of the 500-foot tower. The tower is one of three being constructed for the Constellation Program and Ares/Orion launches. Another tower is seen at right. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009.

The prostate after castration and hormone replacement in a rat model: structural and ultrastructural analysis

PubMed Central

Felix-Patrício, Bruno; Miranda, Alexandre F.; Medeiros, Jorge L.; Gallo, Carla B. M.; Gregório, Bianca M.; de Souza, Diogo B.; Costa, Waldemar S.; Sampaio, Francisco J. B.

2017-01-01

ABSTRACT Purpose: To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. Materials and Methods: 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. Results: Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29μm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. Conclusion: Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations. PMID:28379662

The prostate after castration and hormone replacement in a rat model: structural and ultrastructural analysis.

PubMed

Felix-Patrício, Bruno; Miranda, Alexandre F; Medeiros, Jorge L; Gallo, Carla B M; Gregório, Bianca M; Souza, Diogo B; Costa, Waldemar S; Sampaio, Francisco J B

2017-01-01

To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29μm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations. Copyright® by the International Brazilian Journal of Urology.

Loss of Function of TET2 Cooperates with Constitutively Active KIT in Murine and Human Models of Mastocytosis

PubMed Central

De Vita, Serena; Schneider, Rebekka K.; Garcia, Michael; Wood, Jenna; Gavillet, Mathilde; Ebert, Benjamin L.; Gerbaulet, Alexander; Roers, Axel; Levine, Ross L.; Mullally, Ann; Williams, David A.

2014-01-01

Systemic Mastocytosis (SM) is a clonal disease characterized by abnormal accumulation of mast cells in multiple organs. Clinical presentations of the disease vary widely from indolent to aggressive forms, and to the exceedingly rare mast cell leukemia. Current treatment of aggressive SM and mast cell leukemia is unsatisfactory. An imatinib-resistant activating mutation of the receptor tyrosine kinase KIT (KIT D816V) is most frequently present in transformed mast cells and is associated with all clinical forms of the disease. Thus the etiology of the variable clinical aggressiveness of abnormal mast cells in SM is unclear. TET2 appears to be mutated in primary human samples in aggressive types of SM, suggesting a possible role in disease modification. In this report, we demonstrate the cooperation between KIT D816V and loss of function of TET2 in mast cell transformation and demonstrate a more aggressive phenotype in a murine model of SM when both mutations are present in progenitor cells. We exploit these findings to validate a combination treatment strategy targeting the epigenetic deregulation caused by loss of TET2 and the constitutively active KIT receptor for the treatment of patients with aggressive SM. PMID:24788138

Early effect of boron neutron capture therapy mediated by boronophenylalanine (BPA-BNCT) on mast cells in premalignant tissue and tumors of the hamster cheek pouch.

PubMed

Aromando, Romina F; Trivillin, Verónica A; Heber, Elisa M; Pozzi, Emiliano; Schwint, Amanda E; Itoiz, María E

2010-05-01

Mast cell (MC) activation in the hamster cheek pouch cancerization model is associated with the increase in tumor cell proliferation, mediated in turn by tryptase, a protease released from mast cell granules after activation. Tryptase induces tumor cell proliferation through the activation of PAR-2 (protease activated receptor-2) on the plasma membrane of carcinoma cells. The therapeutic success of boron neutron capture therapy mediated by boronophenylalanine (BPA-BNCT) in tumor control in the hamster cheek pouch oral cancer model has been previously reported by our laboratory. Early effects of BPA-BNCT on tumors of the hamster cheek pouch include a reduction in DNA-synthesis with the concomitant decrease in the proliferation of malignant cells. The aim of the present study was to investigate the early histological changes in mast cells after BPA-BNCT in tumors and premalignant tissue of the hamster cheek pouch. Tumor-bearing pouches were treated with BPA-BNCT or beam only (neutron irradiation without prior administration of the boron compound) and sacrificed 1day after treatment. The samples were fixed in Carnoy fixative and stained with alcian blue-safranin to identify all the populations of mast cells. Total, active and inactive mast cells (MC) were counted in the connective tissue and the adventitious tissue underlying the pouch wall and at the base of the tumors in pouches treated with BPA-BNCT, in keeping with a previously described technique. BPA-BNCT induced a marked reduction in the total number of mast cells in the pouch (p<0.05). This reduction in the total number of mast cells was due to a reduction in mast cells at the base of the tumor (p<0.005) and it occurred at the expense of the active mast cells (p<0.05). A slight reduction that did not reach statistical significance also occurred in the amount of mast cells in the pouch wall (that corresponds to the premalignant tissue in tumor-bearing pouches), and in the adventitious tissue. In this case the reduction was seen in the inactive population. Both BPA-BNCT and beam only elicited a qualitative change in the secretion modality of the granule content. Although further studies are needed to evaluate the subcellular effect of BNCT on mast cell granule secretion, the reduction in cell proliferation induced by BPA-BNCT would be partially due to the decrease in total mast cells in the hamster check pouch. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Leukotriene C4 production by murine mast cells: evidence of a role for extracellular leukotriene A4.

PubMed Central

Dahinden, C A; Clancy, R M; Gross, M; Chiller, J M; Hugli, T E

1985-01-01

The glutathione-containing leukotriene C4 (LTC4) is a major mediator of smooth muscle contraction and is released by mast cells when antigen interacts with cell-bound IgE. Antigen-stimulated mast cells undergo phospholipase activation. We report a pathway of LTC4 production by mast cells that does not require phospholipase activation but depends on the interaction of activated neutrophils with unstimulated mast cells, using as an intermediate extracellular leukotriene A4 (LTA4). The epoxide LTA4 is released by neutrophils and, together with leukotriene B4 and 5-hydroxyeicosatetraenoic acid, constitutes the major lipoxygenase metabolites found in supernatants of stimulated neutrophils. Five minutes after activation of neutrophils by calcium ionophore A23187 we measured 136 pmol of extracellular LTA4 per 10(7) neutrophils (range 40-300, n = 7) by trapping the epoxide with alcohols. Therefore, we conclude that LTA4 is not just an intracellular leukotriene precursor but is released as a lipoxygenase metabolite. LTA4 is known to be stabilized by albumin and is efficiently converted by mast cells into LTC4 even at low LTA4 concentrations. The LTA4 complexed to albumin is converted into LTC4 rapidly and completely within 10-15 min. More than 50% of the LTA4 presented to mast cells is metabolized to LTC4 at concentrations of LTA4 between 0.2 and 2 nmol of LTA4 per 10(7) mast cells. This observation establishes a potential physiologic role for extracellular LTA4. Therefore, interactions between various cell types that release or utilize LTA4 may provide an important metabolic pathway for the production of leukotrienes. PMID:2995976

Design, synthesis, and biological evaluation of 2-substituted-2,3,4,9-tetrahydrospiro-β-carboline-3-carboxylic acid derivatives as first-in-class mast cell stabilizers.

PubMed

Singh, Jatinder; Shah, Ramanpreet; Singh, Dhandeep; Jaggi, Amteshwar S; Singh, Nirmal

2018-05-01

Mast cell degranulation plays a momentous role in myriad diseases like asthma, eczema, allergic rhinitis, and conjunctivitis as well as anaphylactic shock; hence, there is an unmet need for developing new mast cells stabilizers. The reported mast cell stabilizers have a heterocyclic moiety and an acidic group. Furthermore, the role of tryptophan in suppression of mast cell activation is established. Hence, we prepared constrained analogs of tryptophan, which are derivatives of 2,3,4,9-tetrahydrospiro-β-carboline-3-carboxylic acid, and evaluated them for ex vivo inhibition of compound 48/80-induced mast degranulation activity. By comparing IC 50 (μM) values with that of the standard drug sodium cromoglycate (IC 50  = 0.489 ± 0.003 μM), compounds with bulky groups like heptyl (compound 9; IC 50  = 0.389 ± 0.015 μM) and octyl (compound 10; IC 50  = 0.354 ± 0.023 μM) were found to be of similar potency as sodium cromoglycate. Furthermore, the polar group-containing compounds like the chloropropyl (compound 16; IC 50  = 0.382 ± 0.083 μM) and benzoyl derivative (compound 14; IC 50  = 00.469 ± 0.032 μM) were also found to be of similar potency as sodium cromoglycate. This is a seminal study of spiro-β-carboline mast cell stabilization having a wider scope in mast cell research; yet, the mechanism of action remains elusive. © 2018 Deutsche Pharmazeutische Gesellschaft.

MAST (Military Assistance to Safety and Traffic. Report of Test Program by the Interagency Study Group (July-December 1970).

ERIC Educational Resources Information Center

Department of Defense, Washington, DC.

As a joint endeavor by the Departments of Defense, Transportation, and Health, Education, and Welfare to demonstrate military resources and techniques which are utilized in combat, the Military Assistance to Safety and Traffic (MAST) program was pilot-tested in 1970 at five military bases. Undertaken to explore the feasibility of utilizing…

Testing the 'toxin hypothesis of allergy': mast cells, IgE, and innate and acquired immune responses to venoms.

PubMed

Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J

2015-10-01

Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell's viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic type 2 (Th2) immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Testing the "toxin hypothesis of allergy": Mast cells, IgE, and innate and acquired immune responses to venoms*

PubMed Central

Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J.

2015-01-01

Summary Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell’s viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic Th2 immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality. PMID:26210895

Genitourinary mast cells and survival

PubMed Central

Stewart, Julia M.

2015-01-01

Mast cells (MCs) are ubiquitous in the body, but they have historically been associated with allergies, and most recently with regulation of immunity and inflammation. However, it remains a puzzle why so many MCs are located in the diencephalon, which regulates emotions and in the genitourinary tract, including the bladder, prostate, penis, vagina and uterus that hardly ever get allergic reactions. A number of papers have reported that MCs have estrogen, gonadotropin and corticotropin-releasing hormone (CRH) receptors. Moreover, animal experiments have shown that diencephalic MCs increase in number during courting in doves. We had reported that allergic stimulation of nasal MCs leads to hypothalamic-pituitary adrenal (HPA) activation. Interestingly, anecdotal information indicates that female patients with mastocytosis or mast cell activation syndrome may have increased libido. Preliminary evidence also suggests that MCs may have olfactory receptors. MCs may, therefore, have been retained phylogenetically not only to “smell danger”, but to promote survival and procreation. PMID:26813805

Genitourinary mast cells and survival.

PubMed

Theoharides, Theoharis C; Stewart, Julia M

2015-10-01

Mast cells (MCs) are ubiquitous in the body, but they have historically been associated with allergies, and most recently with regulation of immunity and inflammation. However, it remains a puzzle why so many MCs are located in the diencephalon, which regulates emotions and in the genitourinary tract, including the bladder, prostate, penis, vagina and uterus that hardly ever get allergic reactions. A number of papers have reported that MCs have estrogen, gonadotropin and corticotropin-releasing hormone (CRH) receptors. Moreover, animal experiments have shown that diencephalic MCs increase in number during courting in doves. We had reported that allergic stimulation of nasal MCs leads to hypothalamic-pituitary adrenal (HPA) activation. Interestingly, anecdotal information indicates that female patients with mastocytosis or mast cell activation syndrome may have increased libido. Preliminary evidence also suggests that MCs may have olfactory receptors. MCs may, therefore, have been retained phylogenetically not only to "smell danger", but to promote survival and procreation.

Measuring sea surface height with a GNSS-Wave Glider

NASA Astrophysics Data System (ADS)

Morales Maqueda, Miguel Angel; Penna, Nigel T.; Foden, Peter R.; Martin, Ian; Cipollini, Paolo; Williams, Simon D.; Pugh, Jeff P.

2017-04-01

A GNSS-Wave Glider is a novel technique to measure sea surface height autonomously using the Global Navigation Satellite System (GNSS). It consists of an unmanned surface vehicle manufactured by Liquid Robotics, a Wave Glider, and a geodetic-grade GNSS antenna-receiver system, with the antenna installed on a mast on the vehicle's deck. The Wave Glider uses the differential wave motion through the water column for propulsion, thus guaranteeing an, in principle, indefinite autonomy. Solar energy is collected to power all on-board instrumentation, including the GNSS system. The GNSS-Wave Glider was first tested in Loch Ness in 2013, demonstrating that the technology is capable of mapping geoid heights within the loch with an accuracy of a few centimetres. The trial in Loch Ness did not conclusively confirm the reliability of the technique because, during the tests, the state of the water surface was much more benign than would normally be expect in the open ocean. We now report on a first deployment of a GNSS-Wave Glider in the North Sea. The deployment took place in August 2016 and lasted thirteen days, during which the vehicle covered a distance of about 350 nautical miles in the north western North Sea off Great Britain. During the experiment, the GNSS-Wave Glider experienced sea states between 1 (0-0.1 m wave heights) and 5 (2.5-4 m wave heights). The GNSS-Wave Glider data, recorded at 5 Hz frequency, were analysed using a post-processed kinematic GPS-GLONASS precise point positioning (PPP) approach, which were quality controlled using double difference GPS kinematic processing with respect to onshore reference stations. Filtered with a 900 s moving-average window, the PPP heights reveal geoid patterns in the survey area that are very similar to the EGM2008 geoid model, thus demonstrating the potential use of a GNSS-Wave Glider for marine geoid determination. The residual of subtracting the modelled or measured marine geoid from the PPP signal combines information about dynamic topography and sea state. GNSS-Wave Glider data will next be validated against concurrent and co-located satellite altimetry data from the Jason-1, Jason-2, CryoSat-2 and AltiKa missions.

Prospective Randomized Trial of the Military Anti-Shock Garment

DTIC Science & Technology

1987-12-20

No prospective, controlled, randomized studies of !.’AST use were available in the scientific literature. Numerous --ports of MAST use were available...in the scientific literature. ,umerous reports of MAST causing compartment syndromes and amputations did appear in the literature. Beginning in 1983...research funding, computerization of these work sheets became possible, making analysis possible. In that no definitive or scientific clinically controlled

Mast cell sarcoma of the larynx.

PubMed Central

Horny, H P; Parwaresch, M R; Kaiserling, E; Müller, K; Olbermann, M; Mainzer, K; Lennert, K

1986-01-01

A 74 year old woman presented with a primary subglottic tumour. Neither cutaneous mastocytosis (urticaria pigmentosa) nor spread to the bone marrow, liver, or spleen were detected. About two years after initial manifestation of the tumour nodular skin metastases appeared, as well as local recurrence in the larynx. Despite chemotherapy and radiation the disease progressed and was fatal. The terminal phase was characterised by generalisation of the mast cell tumour with diffuse infiltration of bone marrow and, shortly before death, leukaemic transformation. The patient died four years after onset of disease with symptoms of a hemorrhagic diathesis. As far as we know this is the first case of mast cell sarcoma to be reported in man. Images PMID:3088063

LQC control for the Mini-Mast experiment

NASA Technical Reports Server (NTRS)

Montgomery, R. C.; Ghosh, D.

1988-01-01

The Mini-Mast system is briefly reviewed, and results of a simulation study of the LQG control for the Mini-Mast experiment are reported. In particular, attention is given to problems and limitations related to the testing of control laws using reaction mass actuators, such as accounting for force and stroke limits of these devices. The local controller used in the study and the algorithm for converting the force commands of the LQG algorithm to position commands for the reaction mass device are described. It is shown that the LQG generated damping is reduced when a local controller is used and the position command is not saturated; it drops still further when the position command is saturated.

Autonomous Aerial Sensors for Wind Power Meteorology

NASA Astrophysics Data System (ADS)

Giebel, Gregor; Schmidt Paulsen, Uwe; Reuder, Joachim; La Cour-Harbo, Anders; Thomsen, Carsten; Bange, Jens; Buschmann, Marco

2010-05-01

This poster describes a new approach for measurements in wind power meteorology using small unmanned flying platforms. During a week of flying a lighter-than-air vehicle, two small electrically powered aeroplanes and a larger helicopter at the Risø test station at Høvsøre, we will compare wind speed measurements with fixed mast and LIDAR measurements, investigate optimal flight patterns for each measurement task, and measure other interesting meteorological features like the air-sea boundary in the vicinity of the wind farm. In order to prepare the measurement campaign, a workshop is held, soliciting input from various communities. Large-scale wind farms, especially offshore, need an optimisation between installed wind power density and the losses in the wind farm due to wake effects between the turbines. While the wake structure behind single wind turbines onshore is fairly well understood, there are different problems offshore, thought to be due mainly to the low turbulence. Good measurements of the wake and wake structure are not easy to come by, as the use of a met mast is static and expensive, while the use of remote sensing instruments either needs significant access to the turbine to mount an instrument, or is complicated to use on a ship due to the ship's own movement. In any case, a good LIDAR or SODAR will cost many tens of thousands of euros. Another current problem in wind energy is the coming generation of wind turbines in the 10-12 MW class, with tip heights of over 200 m. Very few measurement masts exist to verify our knowledge of atmospheric physics - all that is known is that the boundary layer description we used so far is not valid any more. Here, automated Unmanned Aerial Vehicles (UAVs) could be used as either an extension of current high masts or to build a network of very high ‘masts' in a region of complex terrain or coastal flow conditions. In comparison to a multitude of high masts, UAVs could be quite cost-effective. In order to test this assumption and to test the limits of UAVs for wind power meteorology, this project assembles four different UAVs from four participating groups. Risø will build a lighter-than-air kite with a long tether, Bergen University flies a derivative of the Funjet, a pusher airplane below 1 kg total weight, Mavionics or TU Braunschweig flies the Carolo, a 2m wide two prop model with a pitot tube on the nose, and Aalborg University will use a helicopter for their part. All those platforms will be flown during one week at the Danish national test station for large wind turbines at Høvsøre. The site is strongly instrumented, with 6 masts reaching up to 167m. The comparison of wind speed measurements from planes and fixed masts should give an indication of the accuracy of the measured wind field. A workshop is planned as preparation, where everyone with an interest in the program can give input.

Cutting Edge: The murine high-affinity IgG receptor FcγRIV is sufficient for autoantibody-induced arthritis.

PubMed

Mancardi, David A; Jönsson, Friederike; Iannascoli, Bruno; Khun, Huot; Van Rooijen, Nico; Huerre, Michel; Daëron, Marc; Bruhns, Pierre

2011-02-15

K/BxN serum-induced passive arthritis was reported to depend on the activation of mast cells, triggered by the activating IgG receptor FcγRIIIA, when engaged by IgG1 autoantibodies present in K/BxN serum. This view is challenged by the fact that FcγRIIIA-deficient mice still develop K/BxN arthritis and because FcγRIIIA is the only activating IgG receptor expressed by mast cells. We investigated the contribution of IgG receptors, IgG subclasses, and cells in K/BxN arthritis. We found that the activating IgG2 receptor FcγRIV, expressed only by monocytes/macrophages and neutrophils, was sufficient to induce disease. K/BxN arthritis occurred not only in mast cell-deficient W(sh) mice, but also in mice whose mast cells express no activating IgG receptors. We propose that at least two autoantibody isotypes, IgG1 and IgG2, and two activating IgG receptors, FcγRIIIA and FcγRIV, contribute to K/BxN arthritis, which requires at least two cell types other than mast cells, monocytes/macrophages, and neutrophils.

Evaluation of planetary boundary layer schemes in meso-scale simulations above the North and Baltic Sea

NASA Astrophysics Data System (ADS)

Wurps, Hauke; Tambke, Jens; Steinfeld, Gerald; von Bremen, Lueder

2014-05-01

The development and design of wind energy converters for offshore wind farms require profound knowledge of the wind profile in the lower atmosphere. Especially an accurate and reliable estimation of turbulence, shear and veer are necessary for the prediction of energy production and loads. Currently existing wind energy turbines in the North Sea have hub heights of around 90 m and upper tip heights around 150 m, which is already higher than the highest measurement masts (e.g. FINO1: 103 m). The next generation of wind turbines will clearly outrange these altitudes, so the interest is to examine the atmosphere's properties above the North Sea up to 300 m. Therefore, besides the Prandtl layer also the Ekman layer has to be taken into account, which implies that changes of the wind direction with height become more relevant. For this investigation we use the Weather Research and Forecasting Model (WRF), a meso-scale numerical weather prediction system. In this study we compare different planetary boundary layer (PBL) schemes (MYJ, MYNN, QNSE) with the same high quality input from ECMWF used as boundary conditions (ERA-Interim). It was found in previous studies that the quality of the boundary conditions is crucially important for the accuracy of comparisons between different PBL schemes. This is due to the fact that the major source of meso-scale simulation errors is introduced by the driving boundary conditions and not by the different schemes of the meso-scale model itself. Hence, small differences in results from different PBL schemes can be distorted arbitrarily by coarse input data. For instance, ERA-Interim data leads to meso-scale RMSE values of 1.4 m/s at 100 m height above sea surface with mean wind speeds around 10 m/s, whereas other Reanalysis products lead to RMSEs larger than 2 m/s. Second, we compare our simulations to operational NWP results from the COSMO model (run by the DWD). In addition to the wind profile, also the turbulent kinetic energy (TKE) and the atmosphere's thermal stability are important to estimate power production and loads. Especially the TKE is in the focus of our research since the Master Length Scale of the closure schemes depends on it. A third step is the validation of the results using wind measurements around the North Sea. Because the considered heights are much larger than available data from met masts, we use LiDAR observations (light detection and ranging) and prospectively UAVs (unmanned aerial vehicle).

KSC-08pd3826

NASA Image and Video Library

2008-11-25

CAPE CANAVERAL, Fla. - The new lightning towers are under construction on Launch Pad 39B at NASA’s Kennedy Space Center in Florida. Each of the three new lightning towers will be 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire centenary system. This improved lightning protection system allows for the taller height of the Ares I compared to the space shuttle. Pad B will be the site of the first Ares vehicle launch, including Ares I-X which is targeted for summer of 2009, as part of NASA’s Constellation Program. Photo credit: NASA/Tim Jacobs

KSC-2009-1300

NASA Image and Video Library

2009-01-22

CAPE CANAVERAL, Fla. – A giant crane is used to add additional segments to the new lightning towers on Launch Pad 39B at NASA's Kennedy Space Center in Florida. Three new lightning towers on the pad will be 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Photo credit: NASA/Kim Shiflett

KSC-2009-1339

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane places a 100-foot fiberglass lightning mast on top of the 500-foot tower. The tower is one of three being constructed for the Constellation Program and Ares/Orion launches. Another tower is seen at right. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Jack Pfaller

NMDA receptor modulation by dextromethorphan and acute stress selectively alters electroencephalographic indicators of partial report processing.

PubMed

Weckesser, Lisa J; Enge, Sören; Riedel, Philipp; Kirschbaum, Clemens; Miller, Robert

2017-10-01

Proceeding from a biophysical network model, the present study hypothesized that glutamatergic neurotransmission across the NMDA receptor (NMDAR) plays a key role in visual perception and its modulation by acute stress. To investigate these hypotheses, behavioral and electroencephalographic (EEG) indicators of partial report task processing were assessed in twenty-four healthy young men who randomly received a non-competitive NMDAR antagonist (0.8 mg/kg dextromethorphan, DXM) or a placebo, and concurrently accomplished a stress-induction (MAST) or control protocol in three consecutive sessions. Saliva samples served to quantify cortisol responses to the MAST, whereas a passive auditory oddball paradigm was implemented to verify the impact of DXM on the EEG-derived mismatch negativity component (MMN). DXM administration significantly increased MMN amplitudes but not salivary cortisol concentrations. By contrast, concurrent MAST exposure significantly reduced MMN latencies but also increased cortisol concentrations. With regard to EEG indicators, DXM administration reduced visually "evoked" (30Hz to 50Hz) and "induced" occipital gamma-band activity (70Hz to 100Hz), which was partly compensated by additional MAST exposure. However, neither the interventions nor EEG activity were significantly associated with behavioral partial report sensitivities. In summary, the present data suggest that glutamatergic neurotransmission across the NMDAR is only one among many determinants of intact visual perception. Accordingly, therapeutic doses of DXM and their inhibitory modulation by stress probably yield more pronounced electroencephalographic as compared with behavioural effects. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Mast cells enhance T cell activation: Importance of mast cell-derived TNF

NASA Astrophysics Data System (ADS)

Nakae, Susumu; Suto, Hajime; Kakurai, Maki; Sedgwick, Jonathon D.; Tsai, Mindy; Galli, Stephen J.

2005-05-01

Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production. allergy | asthma | autoimmunity | cytokines | immune response

Eigensystem realization algorithm modal identification experiences with mini-mast

NASA Technical Reports Server (NTRS)

Pappa, Richard S.; Schenk, Axel; Noll, Christopher

1992-01-01

This paper summarizes work performed under a collaborative research effort between the National Aeronautics and Space Administration (NASA) and the German Aerospace Research Establishment (DLR, Deutsche Forschungsanstalt fur Luft- und Raumfahrt). The objective is to develop and demonstrate system identification technology for future large space structures. Recent experiences using the Eigensystem Realization Algorithm (ERA), for modal identification of Mini-Mast, are reported. Mini-Mast is a 20 m long deployable space truss used for structural dynamics and active vibration-control research at the Langley Research Center. A comprehensive analysis of 306 frequency response functions (3 excitation forces and 102 displacement responses) was performed. Emphasis is placed on two topics of current research: (1) gaining an improved understanding of ERA performance characteristics (theory vs. practice); and (2) developing reliable techniques to improve identification results for complex experimental data. Because of nonlinearities and numerous local modes, modal identification of Mini-Mast proved to be surprisingly difficult. Methods were available, ERA, for obtaining detailed, high-confidence results.

Mast cells and histamine alter intestinal permeability during malaria parasite infection.

PubMed

Potts, Rashaun A; Tiffany, Caitlin M; Pakpour, Nazzy; Lokken, Kristen L; Tiffany, Connor R; Cheung, Kong; Tsolis, Renée M; Luckhart, Shirley

2016-03-01

Co-infections with malaria and non-typhoidal Salmonella serotypes (NTS) can present as life-threatening bacteremia, in contrast to self-resolving NTS diarrhea in healthy individuals. In previous work with our mouse model of malaria/NTS co-infection, we showed increased gut mastocytosis and increased ileal and plasma histamine levels that were temporally associated with increased gut permeability and bacterial translocation. Here, we report that gut mastocytosis and elevated plasma histamine are also associated with malaria in an animal model of falciparum malaria, suggesting a broader host distribution of this biology. In support of mast cell function in this phenotype, malaria/NTS co-infection in mast cell-deficient mice was associated with a reduction in gut permeability and bacteremia. Further, antihistamine treatment reduced bacterial translocation and gut permeability in mice with malaria, suggesting a contribution of mast cell-derived histamine to GI pathology and enhanced risk of bacteremia during malaria/NTS co-infection. Copyright © 2015 Elsevier GmbH. All rights reserved.

Decreased number of mast cells infiltrating into needle biopsy specimens leads to a better prognosis of prostate cancer

PubMed Central

Nonomura, N; Takayama, H; Nishimura, K; Oka, D; Nakai, Y; Shiba, M; Tsujimura, A; Nakayama, M; Aozasa, K; Okuyama, A

2007-01-01

Mast cell infiltration is often observed around human tumours. Inflammatory cells such as macrophages, neutrophils and mast cells infiltrating around tumours are known to contribute to tumour growth; however, the clinical significance of mast cell invasion in prostate cancer (PCa) has not been investigated. Mast cell infiltration was evaluated in 104 patients (age range, 45–88 years; median, 72 years), who underwent needle biopsy of the prostate and were confirmed to have PCa. Needle biopsy specimens of prostate were sliced into 5-μm-thick sections and immunostained for mast cells with monoclonal antibody against mast cell-specific tryptase. Mast cells were counted systematically under a microscope (× 400 magnification), and the relations between mast cell numbers and clinicopathologic findings were evaluated. The mast cell count was evaluated for prognostic value by multivariate analysis. Mast cells were immunostained around the cancer foci. The median number of mast cells in each case was 16. The mast cell count was higher around cancer foci in patients with higher Gleason scores than in those with low Gleason scores. The mast cell number correlated well with clinical stage (P<0.001). Prostate-specific antigen-free survival of patients with higher mast cell counts was better than that in patients with lower mast cell counts (P<0.001). Multivariate analysis revealed that mast cell count was a significant prognostic factor (P<0.005). The number of mast cells infiltrating around cancer foci in prostate biopsy specimens can be a significant prognostic factor of PCa. PMID:17848955

Approaches for Analyzing the Roles of Mast Cells and Their Proteases In Vivo

PubMed Central

Galli, Stephen J.; Tsai, Mindy; Marichal, Thomas; Tchougounova, Elena; Reber, Laurent L.; Pejler, Gunnar

2016-01-01

The roles of mast cells in health and disease remain incompletely understood. While the evidence that mast cells are critical effector cells in IgE-dependent anaphylaxis and other acute IgE-mediated allergic reactions seems unassailable, studies employing various mice deficient in mast cells or mast cell-associated proteases have yielded divergent conclusions about the roles of mast cells or their proteases in certain other immunological responses. Such “controversial” results call into question the relative utility of various older versus newer approaches to ascertain the roles of mast cells and mast cell proteases in vivo. This review discusses how both older and more recent mouse models have been used to investigate the functions of mast cells and their proteases in health and disease. We particularly focus on settings in which divergent conclusions about the importance of mast cells and their proteases have been supported by studies that employed different models of mast cell or mast cell protease deficiency. We think that two major conclusions can be drawn from such findings: (1) no matter which models of mast cell or mast cell protease deficiency one employs, the conclusions drawn from the experiments always should take into account the potential limitations of the models (particularly abnormalities affecting cell types other than mast cells) and (2) even when analyzing a biological response using a single model of mast cell or mast cell protease deficiency, details of experimental design are critical in efforts to define those conditions under which important contributions of mast cells or their proteases can be identified. PMID:25727288

Proteome analysis identifies L1CAM/CD171 and DPP4/CD26 as novel markers of human skin mast cells.

PubMed

Gschwandtner, M; Paulitschke, V; Mildner, M; Brunner, P M; Hacker, S; Eisenwort, G; Sperr, W R; Valent, P; Gerner, C; Tschachler, E

2017-01-01

The function of skin mast cells has been well documented in IgE-mediated allergic reactions, whereas other mast cell functions are poorly defined. This study aimed at identifying novel mast cell proteins by proteome analysis of primary human skin mast cells. The proteome of skin mast cells was compared to other cell types and analyzed using bioinformatics. The expression and function of two proteins hitherto not described in skin mast cells was investigated in isolated mast cells as well as in mast cells in situ. Within the mast cell proteome, we identified 49 highly expressed proteins previously not described in mast cells; 21 of these proteins were found to be selectively expressed in mast cells. Two proteins, the neural cell adhesion molecule L1 and dipeptidyl peptidase 4, were further studied. L1 was found to be highly expressed in mast cells in normal, psoriasis, and mastocytosis skin. Dipeptidyl peptidase 4 was found to be expressed in mast cells in normal, psoriasis, and mastocytosis skin as well as in bone marrow mast cells in patients with systemic mastocytosis. In normal skin, mast cells were identified as a major source of dipeptidyl peptidase 4 and we also found that skin mast cells and fibroblasts secrete an active form of this enzyme. In a systematic proteomics approach we identified two novel mast cell proteins potentially relevant to skin homeostasis: neural cell adhesion molecule L1 and dipeptidyl peptidase 4. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dectin-1-mediated signaling leads to characteristic gene expressions and cytokine secretion via spleen tyrosine kinase (Syk) in rat mast cells.

PubMed

Kimura, Yukihiro; Chihara, Kazuyasu; Honjoh, Chisato; Takeuchi, Kenji; Yamauchi, Shota; Yoshiki, Hatsumi; Fujieda, Shigeharu; Sada, Kiyonao

2014-11-07

Dectin-1 recognizes β-glucan and plays important roles for the antifungal immunity through the activation of spleen tyrosine kinase (Syk) in dendritic cells or macrophages. Recently, expression of Dectin-1 was also identified in human and mouse mast cells, although its physiological roles were largely unknown. In this report, rat mast cell line RBL-2H3 was analyzed to investigate the molecular mechanism of Dectin-1-mediated activation and responses of mast cells. Treatment of cells with Dectin-1-specific agonist curdlan induced tyrosine phosphorylation of cellular proteins and the interaction of Dectin-1 with the Src homology 2 domain of Syk. These responses depended on tyrosine phosphorylation of the hemi-immunoreceptor tyrosine-based activation motif in the cytoplasmic tail of Dectin-1, whereas they were independent of the γ-subunit of high-affinity IgE receptor. DNA microarray and real-time PCR analyses showed that Dectin-1-mediated signaling stimulated gene expression of transcription factor Nfkbiz and inflammatory cytokines, such as monocyte chemoattractant protein-1, IL-3, IL-4, IL-13, and tumor necrosis factor (TNF)-α. The response was abrogated by pretreatment with Syk inhibitor R406. These results suggest that Syk is critical for Dectin-1-mediated activation of mast cells, although the signaling differs from that triggered by FcϵRI activation. In addition, these gene expressions induced by curdlan stimulation were specifically observed in mast cells, suggesting that Dectin-1-mediated signaling of mast cells offers new insight into the antifungal immunity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Physiological relevance of LL-37 induced bladder inflammation and mast cells.

PubMed

Oottamasathien, Siam; Jia, Wanjian; Roundy, Lindsi McCoard; Zhang, Jianxing; Wang, Li; Ye, Xiangyang; Hill, A Cameron; Savage, Justin; Lee, Wong Yong; Hannon, Ann Marie; Milner, Sylvia; Prestwich, Glenn D

2013-10-01

We established the physiological relevance of LL-37 induced bladder inflammation. We hypothesized that 1) human urinary LL-37 is increased in pediatric patients with spina bifida, 2) LL-37 induced inflammation occurs in our mouse model via urothelial binding and is dose dependent and 3) LL-37 induced inflammation involves mast cells. To test our first hypothesis, we obtained urine samples from 56 pediatric patients with spina bifida and 22 normal patients. LL-37 was measured by enzyme-linked immunosorbent assay. Our second hypothesis was tested in C57Bl/6 mice challenged with 7 LL-37 concentrations intravesically for 1 hour. At 24 hours tissues were examined histologically and myeloperoxidase assay was done to quantitate inflammation. In separate experiments fluorescent LL-37 was instilled and tissues were obtained immediately (time = 0) and at 24 hours (time = 24). To test our final hypothesis, we performed immunohistochemistry for mast cell tryptase and evaluated 5 high power fields per bladder to determine the mean number of mast cells per mm(2). Urinary LL-37 was 89-fold higher in patients with spina bifida. Mouse LL-37 dose escalation experiments revealed increased inflammation at higher LL-37 concentrations. Fluorescent LL-37 demonstrated global urothelial binding at time = 0 but was not visible at time = 24. Immunohistochemistry for tryptase revealed mast cell infiltration in all tissue layers. At higher concentrations the LL-37 challenge led to significantly greater mast cell infiltration. Urinary LL-37 was significantly increased in pediatric patients with spina bifida. To our knowledge we report for the first time that LL-37 can elicit profound, dose dependent bladder inflammation involving the urothelium. Finally, inflammation propagation involves mast cells. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Physiological Relevance of LL-37 Induced Bladder Inflammation and Mast Cells

PubMed Central

Roundy, Lindsi McCoard; Zhang, Jianxing; Wang, Li; Ye, Xiangyang; Hill, A. Cameron; Savage, Justin; Lee, Wong Yong; Hannon, Ann Marie; Milner, Sylvia; Prestwich, Glenn D.

2014-01-01

Purpose We established the physiological relevance of LL-37 induced bladder inflammation. We hypothesized that 1) human urinary LL-37 is increased in pediatric patients with spina bifida, 2) LL-37 induced inflammation occurs in our mouse model via urothelial binding and is dose dependent and 3) LL-37 induced inflammation involves mast cells. Materials and Methods To test our first hypothesis, we obtained urine samples from 56 pediatric patients with spina bifida and 22 normal patients. LL-37 was measured by enzyme-linked immunosorbent assay. Our second hypothesis was tested in C57Bl/6 mice challenged with 7 LL-37 concentrations intravesically for 1 hour. At 24 hours tissues were examined histologically and myeloperoxidase assay was done to quantitate inflammation. In separate experiments fluorescent LL-37 was instilled and tissues were obtained immediately (time = 0) and at 24 hours (time = 24). To test our final hypothesis, we performed immunohistochemistry for mast cell tryptase and evaluated 5 high power fields per bladder to determine the mean number of mast cells per mm2. Results Urinary LL-37 was 89-fold higher in patients with spina bifida. Mouse LL-37 dose escalation experiments revealed increased inflammation at higher LL-37 concentrations. Fluorescent LL-37 demonstrated global urothelial binding at time = 0 but was not visible at time = 24. Immunohistochemistry for tryptase revealed mast cell infiltration in all tissue layers. At higher concentrations the LL-37 challenge led to significantly greater mast cell infiltration. Conclusions Urinary LL-37 was significantly increased in pediatric patients with spina bifida. To our knowledge we report for the first time that LL-37 can elicit profound, dose dependent bladder inflammation involving the urothelium. Finally, inflammation propagation involves mast cells. PMID:23313203

Kounis Syndrome During Anesthesia: Presentation of Indolent Systemic Mastocytosis: A Case Report.

PubMed

de la Fuente Tornero, Elena; Vega Castro, Arantza; de Sierra Hernández, Pedro Álvarez; Balaguer Recena, Javier; Zaragoza Casares, Sofía Carmen; Serrano Baylin, Francisco Miguel; Gallardo Culebradas, Paloma; Amorós Alfonso, Beatriz; Rodríguez Fraile, Jose Ramón

2017-05-01

Mastocytosis comprises a heterogeneous group of disorders characterized by mast cell accumulation and proliferation in distinct organs. Kounis syndrome is defined as the concurrence of acute coronary syndromes with mast cell activation in a setting of allergic or hypersensitivity reactions. This is the first reported case of an intraoperative Kounis syndrome as the onset of an indolent systemic mastocytosis probably triggered by succinylated gelatin infusion during general anesthesia. The presentation of this case is intended to contribute to the knowledge of mastocytosis and Kounis syndrome at the time of diagnostic workup during intraoperative anaphylaxis or myocardial ischemia.

Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells.

PubMed

Park, Hyo-Hyun; Lee, Soyoung; Son, Hee-Young; Park, Seung-Bin; Kim, Mi-Sun; Choi, Eun-Ju; Singh, Thoudam S K; Ha, Jeoung-Hee; Lee, Maan-Gee; Kim, Jung-Eun; Hyun, Myung Chul; Kwon, Taeg Kyu; Kim, Yeo Hyang; Kim, Sang-Hyun

2008-10-01

Mast cells participate in allergy and inflammation by secreting inflammatory mediators such as histamine and proinflammatory cytokines. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and antiinflammatory actions. However, effect of flavonoids on the release of histamine and proinflammatory mediator, and their comparative mechanism of action in mast cells were not well defined. Here, we compared the effect of six flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) on the mast cell-mediated allergic inflammation. Fisetin, kaempferol, myricetin, quercetin, and rutin inhibited IgE or phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-mediated histamine release in RBL-2H3 cells. These five flavonoids also inhibited elevation of intracellular calcium. Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation. Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. The pharmacological actions of these flavonoids suggest their potential activity for treatment of allergic inflammatory diseases through the down-regulation of mast cell activation.

Phoenix Lander on Mars with Surrounding Terrain, Vertical Projection

NASA Technical Reports Server (NTRS)

2008-01-01

This view is a vertical projection that combines more than 500 exposures taken by the Surface Stereo Imager camera on NASA's Mars Phoenix Lander and projects them as if looking down from above.

The black circle on the spacecraft is where the camera itself is mounted on the lander, out of view in images taken by the camera. North is toward the top of the image. The height of the lander's meteorology mast, extending toward the southwest, appears exaggerated because that mast is taller than the camera mast.

This view in approximately true color covers an area about 30 meters by 30 meters (about 100 feet by 100 feet). The landing site is at 68.22 degrees north latitude, 234.25 degrees east longitude on Mars.

The ground surface around the lander has polygonal patterning similar to patterns in permafrost areas on Earth.

This view comprises more than 100 different Stereo Surface Imager pointings, with images taken through three different filters at each pointing. The images were taken throughout the period from the 13th Martian day, or sol, after landing to the 47th sol (June 5 through July 12, 2008). The lander's Robotic Arm is cut off in this mosaic view because component images were taken when the arm was out of the frame.

The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

Mast Cells: Key Contributors to Cardiac Fibrosis

PubMed Central

Widiapradja, Alexander

2018-01-01

Historically, increased numbers of mast cells have been associated with fibrosis in numerous cardiac pathologies, implicating mast cells in the development of cardiac fibrosis. Subsequently, several approaches have been utilised to demonstrate a causal role for mast cells in animal models of cardiac fibrosis including mast cell stabilising compounds, rodents deficient in mast cells, and inhibition of the actions of mast cell-specific proteases such as chymase and tryptase. Whilst most evidence supports a pro-fibrotic role for mast cells, there is evidence that in some settings these cells can oppose fibrosis. A major gap in our current understanding of cardiac mast cell function is identification of the stimuli that activate these cells causing them to promote a pro-fibrotic environment. This review will present the evidence linking mast cells to cardiac fibrosis, as well as discuss the major questions that remain in understanding how mast cells contribute to cardiac fibrosis. PMID:29329223

Breeding system and pollen limitation in the masting tree Sorbus aucuparia L. (Rosaceae) in the NW Iberian Peninsula

NASA Astrophysics Data System (ADS)

Pías, Beatriz; Guitián, Pablo

2006-01-01

Mast seeding or masting is the supra-annual periodic production of a large number of seeds by long-lived plants. It has been suggested that this may be a strategy to increase pollination efficiency. Sorbus aucuparia is a masting tree typically showing rather low fruit set, though with some variation among years and populations, together with marked among-year variation in flower and fruit production. Here we report a study of the reproductive biology and insect-visitor spectrum of S. aucuparia in the NW Iberian Peninsula. Results obtained over a 4-year period indicate marked self-incompatibility, so that fruit set is strongly dependent on pollinator service. Nevertheless, fruit and seed set were not limited by pollen supply in any of the years of study, since fruit and seed set after manual cross-pollination were no higher than after natural pollination. Inflorescences were visited by diverse insect species. There was no significant correlation between fruit set and insect visit frequency. Taken together, these findings indicate that the rather low fruit and seed sets observed in this species, and the spatiotemporal variation in these parameters, must be attributed to other factors, such as abiotic resource availability. We conclude that masting in S. aucuparia is probably not a strategy for increasing pollination efficiency.

Evaluation of a multiple food specific IgE antibody test compared to parental perception, allergy skin tests and RAST.

PubMed

Adler, B R; Assadullahi, T; Warner, J A; Warner, J O

1991-11-01

This study was set up to evaluate the food panel of a multiple specific IgE antibody assay in 67 atopic asthmatic children by comparing it to the conventional radioallergosorbent test (RAST) and skin-prick tests (SPT) and then comparing the results of these investigations with the parents' perceptions of food related problems. Fifteen food specific IgE antibodies were measured using the multiple chemiluminescence assay (MAST-CLA). IgE antibodies to five of these food allergens were also measured by conventional RAST and SPTs were performed in 43 using 11 standardized food extracts matched to the multiple allergosorbent chemiluminescent assay (MAST-CLA) profile. SPT and MAST-CLA results showed good agreement with one another, range 68.8-96.7% (average 87%), with significant correlation for most allergens tested. MAST-CLA was discrepant with RAST and/or SPTs in 58/210 (27.6%). A questionnaire was sent to the parents to determine their perception of food related symptoms. Sixty-two (92%) questionnaire replies were received, of which 56% reported symptoms with food. The most frequent symptom perceived to be due to food intolerance was behavioural disturbance. The commonest foods implicated were additives (39%), egg (27%), milk (26%), chocolate (23%) and orange (15%). History, SPT, MAST-CLA and RAST were compared for five allergens in 42 patients (210 values). In 14/210 (6.7%), all the tests were negative despite reported symptoms. Conversely in 49/210 (23.3%) at least one test was positive without symptoms. This study did not support a benefit of multipole testing instead of individually selected RASTs or SPTs.(ABSTRACT TRUNCATED AT 250 WORDS)

Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity.

PubMed

Feyerabend, Thorsten B; Weiser, Anne; Tietz, Annette; Stassen, Michael; Harris, Nicola; Kopf, Manfred; Radermacher, Peter; Möller, Peter; Benoist, Christophe; Mathis, Diane; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2011-11-23

Immunological functions of mast cells remain poorly understood. Studies in Kit mutant mice suggest key roles for mast cells in certain antibody- and T cell-mediated autoimmune diseases. However, Kit mutations affect multiple cell types of both immune and nonimmune origin. Here, we show that targeted insertion of Cre-recombinase into the mast cell carboxypeptidase A3 locus deleted mast cells in connective and mucosal tissues by a genotoxic Trp53-dependent mechanism. Cre-mediated mast cell eradication (Cre-Master) mice had, with the exception of a lack of mast cells and reduced basophils, a normal immune system. Cre-Master mice were refractory to IgE-mediated anaphylaxis, and this defect was rescued by mast cell reconstitution. This mast cell-deficient strain was fully susceptible to antibody-induced autoimmune arthritis and to experimental autoimmune encephalomyelitis. Differences comparing Kit mutant mast cell deficiency models to selectively mast cell-deficient mice call for a systematic re-evaluation of immunological functions of mast cells beyond allergy. Copyright © 2011 Elsevier Inc. All rights reserved.

Discovery of Aryl Aminoquinazoline Pyridones as Potent, Selective, and Orally Efficacious Inhibitors of Receptor Tyrosine Kinase c-Kit

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

Hu, Essa; Tasker, Andrew; White, Ryan D.

2008-12-09

Inhibition of c-Kit has the potential to treat mast cell associated fibrotic diseases. We report the discovery of several aminoquinazoline pyridones that are potent inhibitors of c-Kit with greater than 200-fold selectivity against KDR, p38, Lck, and Src. In vivo efficacy of pyridone 16 by dose-dependent inhibition of histamine release was demonstrated in a rodent pharmacodynamic model of mast cell activation.

Testing the Deployment Repeatability of a Precision Deployable Boom Prototype for the Proposed SWOT Karin Instrument

NASA Technical Reports Server (NTRS)

Agnes, Gregory S.; Waldman, Jeff; Hughes, Richard; Peterson, Lee D.

2015-01-01

NASA's proposed Surface Water Ocean Topography (SWOT) mission, scheduled to launch in 2020, would provide critical information about Earth's oceans, ocean circulation, fresh water storage, and river discharge. The mission concept calls for a dual-antenna Ka-band radar interferometer instrument, known as KaRIn, that would map the height of water globally along two 50 km wide swaths. The KaRIn antennas, which would be separated by 10 meters on either side of the spacecraft, would need to be precisely deployable in order to meet demanding pointing requirements. Consequently, an effort was undertaken to design build and prototype a precision deployable Mast for the KaRIn instrument. Each mast was 4.5-m long with a required dilitation stability of 2.5 microns over 3 minutes. It required a minimum first mode of 7 Hz. Deployment repeatability was less than +/- 7 arcsec in all three rotation directions. Overall mass could not exceed 41.5 Kg including any actuators and thermal blanketing. This set of requirements meant the boom had to be three times lighter and two orders of magnitude more precise than the existing state of the art for deployable booms.

Mast cells mediate the immune suppression induced by dermal exposure to JP-8 jet fuel.

PubMed

Limón-Flores, Alberto Y; Chacón-Salinas, Rommel; Ramos, Gerardo; Ullrich, Stephen E

2009-11-01

Applying jet propulsion-8 (JP-8) jet fuel to the skin of mice induces immune suppression. Applying JP-8 to the skin of mice suppresses T-cell-mediated immune reactions including, contact hypersensitivity (CHS) delayed-type hypersensitivity and T-cell proliferation. Because dermal mast cells play an important immune regulatory role in vivo, we tested the hypothesis that mast cells mediate jet fuel-induced immune suppression. When we applied JP-8 to the skin of mast cell deficient mice CHS was not suppressed. Reconstituting mast cell deficient mice with wild-type bone marrow derived mast cells (mast cell "knock-in mice") restored JP-8-induced immune suppression. When, however, mast cells from prostaglandin E(2) (PGE(2))-deficient mice were used, the ability of JP-8 to suppress CHS was not restored, indicating that mast cell-derived PGE(2) was activating immune suppression. Examining the density of mast cells in the skin and lymph nodes of JP-8-treated mice indicated that jet fuel treatment caused an initial increase in mast cell density in the skin, followed by increased numbers of mast cells in the subcutaneous space and then in draining lymph nodes. Applying JP-8 to the skin increased mast cell expression of CXCR4, and increased the expression of CXCL12 by draining lymph node cells. Because CXCL12 is a chemoattractant for CXCR4+ mast cells, we treated JP-8-treated mice with AMD3100, a CXCR4 antagonist. AMD3100 blocked the mobilization of mast cells to the draining lymph node and inhibited JP-8-induced immune suppression. Our findings demonstrate the importance of mast cells in mediating jet fuel-induced immune suppression.

Mast Cells Mediate the Immune Suppression Induced by Dermal Exposure to JP-8 Jet Fuel

PubMed Central

Limón-Flores, Alberto Y.; Chacón-Salinas, Rommel; Ramos, Gerardo; Ullrich, Stephen E.

2009-01-01

Applying jet propulsion-8 (JP-8) jet fuel to the skin of mice induces immune suppression. Applying JP-8 to the skin of mice suppresses T-cell–mediated immune reactions including, contact hypersensitivity (CHS) delayed-type hypersensitivity and T-cell proliferation. Because dermal mast cells play an important immune regulatory role in vivo, we tested the hypothesis that mast cells mediate jet fuel–induced immune suppression. When we applied JP-8 to the skin of mast cell deficient mice CHS was not suppressed. Reconstituting mast cell deficient mice with wild-type bone marrow derived mast cells (mast cell “knock-in mice”) restored JP-8–induced immune suppression. When, however, mast cells from prostaglandin E2 (PGE2)–deficient mice were used, the ability of JP-8 to suppress CHS was not restored, indicating that mast cell–derived PGE2 was activating immune suppression. Examining the density of mast cells in the skin and lymph nodes of JP-8-treated mice indicated that jet fuel treatment caused an initial increase in mast cell density in the skin, followed by increased numbers of mast cells in the subcutaneous space and then in draining lymph nodes. Applying JP-8 to the skin increased mast cell expression of CXCR4, and increased the expression of CXCL12 by draining lymph node cells. Because CXCL12 is a chemoattractant for CXCR4+ mast cells, we treated JP-8-treated mice with AMD3100, a CXCR4 antagonist. AMD3100 blocked the mobilization of mast cells to the draining lymph node and inhibited JP-8–induced immune suppression. Our findings demonstrate the importance of mast cells in mediating jet fuel–induced immune suppression. PMID:19726579

Mechanisms mediating Nitroglycerin-induced Delayed Onset Hyperalgesia in the Rat

PubMed Central

Ferrari, Luiz F.; Levine, Jon D.; Green, Paul G.

2016-01-01

Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN’s very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ~30 min in male and ~45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggest potential novel risk factors and targets for the treatment of migraine. PMID:26779834

Is a subtype of autism an allergy of the brain?

PubMed

Theoharides, Theoharis C

2013-05-01

Autism spectrum disorders (ASDs) are characterized by deficits in social communication and language and the presence of repetitive behaviors that affect as many as 1 in 50 US children. Perinatal stress and environmental factors appear to play a significant role in increasing the risk for ASDs. There is no definitive pathogenesis, which therefore significantly hinders the development of a cure. We aimed to identify publications using basic or clinical data that suggest a possible association between atopic symptoms and ASDs, as well as evidence of how such an association could lead to brain disease, that may explain the pathogenesis of ASD. PubMed was searched for articles published since 1995 that reported any association between autism and/or ASDs and any one of the following terms: allergy, atopy, brain, corticotropin-releasing hormone, cytokines, eczema, food allergy, food intolerance, gene mutation, inflammation, mast cells, mitochondria, neurotensin, phenotype, stress, subtype, or treatment. Children with ASD respond disproportionally to stress and also present with food and skin allergies that involve mast cells. Brain mast cells are found primarily in the hypothalamus, which participates in the regulation of behavior and language. Corticotropin-releasing hormone is secreted from the hypothalamus under stress and, together with neurotensin, stimulates brain mast cells that could result in focal brain allergy and neurotoxicity. Neurotensin is significantly increased in serum of children with ASD and stimulates mast cell secretion of mitochondrial adenosine triphosphate and DNA, which is increased in these children; these mitochondrial components are misconstrued as innate pathogens, triggering an autoallergic response in the brain. Gene mutations associated with higher risk of ASD have been linked to reduction of the phosphatase and tensin homolog, which inhibits the mammalian target of rapamycin (mTOR). These same mutations also lead to mast cell activation and proliferation. Corticotropin-releasing hormone, neurotensin, and environmental toxins could further trigger the already activated mTOR, leading to superstimulation of brain mast cells in those areas responsible for ASD symptoms. Preliminary evidence indicates that the flavonoid luteolin is a stronger inhibitor of mTOR than rapamycin and is a potent mast cell blocker. Activation of brain mast cells by allergic, environmental, immune, neurohormonal, stress, and toxic triggers, especially in those areas associated with behavior and language, lead to focal brain allergies and subsequent focal encephalitis. This possibility is more likely in the subgroup of patients with ASD susceptibility genes that also involve mast cell activation. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Mast cell dynamics in the house rat (Rattus rattus) ovary during estrus cycle, pregnancy and lactation.

PubMed

Batth, B K; Parshad, R K

2000-02-01

The distribution of mast cells in various ovarian compartments was studied during different stages of the reproductive cycles in Rattus rattus. Two types of mast cell populations were recognized with light microscopy i.e., light purple and deep purple, the latter also includes deeply stained cells with extruded granules. Mast cells identified by electron microscopy showed the ultrastructural features during granule formation and release of their content. Significantly higher numbers of mast cells per unit area of ovary were seen at estrus and diestrus. Numbers of mast cells also remained high during pregnancy with possible involvement of mast cell products in vascularization of corpora lutea. A positive correlation existed between mast cell counts and embryo number during pregnancy. However, numbers of mast cells declined significantly after parturition.

Increased leukotriene E4 excretion in systemic mastocytosis.

PubMed

Butterfield, Joseph H

2010-06-01

Cysteinyl leukotrienes such as LTE(4) are produced by mast cells, neutrophils, eosinophils, and macrophages. LTE(4) levels have not been reported in systemic mastocytosis, a disorder with a large increase in mast cell numbers. Urinary LTE(4) from patients referred for symptoms potentially due to mast cell degranulation or systemic mastocytosis was measured by a commercial cysteinyl leukotriene enzyme immunoassay kit. The diagnosis of systemic mastocytosis was established using current World Health Organization criteria. Compared with a control group of patients with various potential mast cell-related symptoms (e.g., "spells"), patients with systemic mastocytosis had a significant (P=.01) increase in urinary LTE(4) excretion, whether expressed as LTE(4) ng/g creatinine or as LTE(4) ng/24h. There was a moderate correlation of LTE(4) ng/24h with excretion of N-methyl histamine and serum tryptase but not with urinary 11beta-prostaglandin F(2alpha) (11beta-PGF(2alpha)) excretion. LTE(4) excretion is increased in patients with systemic mastocytosis and potentially contributes to clinical symptoms. Copyright 2010 Elsevier Inc. All rights reserved.

Soil temperature investigations using satellite acquired thermal-infrared data in semi-arid regions. Thesis. Final Report; [Utah

NASA Technical Reports Server (NTRS)

Day, R. L.; Petersen, G. W.

1983-01-01

Thermal-infrared data from the Heat Capacity Mapping Mission satellite were used to map the spatial distribution of diurnal surface temperatures and to estimate mean annual soil temperatures (MAST) and annual surface temperature amplitudes (AMP) in semi-arid east central Utah. Diurnal data with minimal snow and cloud cover were selected for five dates throughout a yearly period and geometrically co-registered. Rubber-sheet stretching was aided by the WARP program which allowed preview of image transformations. Daytime maximum and nighttime minimum temperatures were averaged to generation average daily temperature (ADT) data set for each of the five dates. Five ADT values for each pixel were used to fit a sine curve describing the theoretical annual surface temperature response as defined by a solution of a one-dimensinal heat flow equation. Linearization of the equation produced estimates of MAST and AMP plus associated confidence statistics. MAST values were grouped into classes and displayed on a color video screen. Diurnal surface temperatures and MAST were primarily correlated with elevation.

Deficient Differentiation of Mast Cells in the Skin of mi/mi Mice

PubMed Central

Kasugai, Tsutomu; Oguri, Kayoko; Jippo-Kanemoto, Tomoko; Morimoto, Masahiro; Yamatodani, Atsushi; Yoshida, Keiichi; Ebi, Yoshitaka; Isozaki, Koji; Tei, Hideki; Tsujimura, Tohru; Nomura, Shintaro; Okayama, Minoru; Kitamura, Yukihiko

1993-01-01

The staining property of skin mast cells changed from Alcian blue+/berberine sulfate- to Alcian blue +/berberine sulfate+ in the skin of normal (+/+) and Wv/Wv mice. In contrast, this change did not occur in the skin of mi/mi mice. Heparin content and histamine content per a mi/mi skin mast cell were estimated to be 34% and 18% those of a +/+ skin mast cell, respectively. The low heparin content of mi/mi skin mast cells seemed to be consistent with the Alcian blue+/berberine sulfate- staining property. Expression of genes encoding mast cell-specific proteolytic enzymes was examined by Northern blotting and in situ hybridization. Messenger RNA of mast cell carboxypeptidase A was expressed most of all by +/+, WV Wv/W+ and mi/mi skin mast cells, but mRNA of mouse mast cell protease (MMCP)-6 was expressed by approximately a half of +/+ and Wv/Wv skin mast cells and by only 3% of mi/mi skin mast cells. A significant amount of MMCP-2 mRNA was not expressed in the skin of all +/+, Wv/Wv and mi/mi mice. This shows the presence of at least three phenotypes in skin mast cells of mice: berberine sulfate+/MMCP-6+, berberine sulfate+/MMCP-6-, and berberine sulfate-/ MMCP-6-. The in situ hybridization of mRNA of mast cell-specific proteolytic enzymes seemed to be useful to describe abnormalities of mast cell differentiation in the skin of mi/mi mice. ImagesFigure 4Figure 5 PMID:8238251

Sources and methods to reconstruct past masting patterns in European oak species.

PubMed

Szabó, Péter

2012-01-01

The irregular occurrence of good seed years in forest trees is known in many parts of the world. Mast year frequency in the past few decades can be examined through field observational studies; however, masting patterns in the more distant past are equally important in gaining a better understanding of long-term forest ecology. Past masting patterns can be studied through the examination of historical written sources. These pose considerable challenges, because data in them were usually not recorded with the aim of providing information about masting. Several studies examined masting in the deeper past, however, authors hardly ever considered the methodological implications of using and combining various source types. This paper provides a critical overview of the types of archival written that are available for the reconstruction of past masting patterns for European oak species and proposes a method to unify and evaluate different types of data. Available sources cover approximately eight centuries and can be put into two basic categories: direct observations on the amount of acorns and references to sums of money received in exchange for access to acorns. Because archival sources are highly different in origin and quality, the optimal solution for creating databases for past masting data is a three-point scale: zero mast, moderate mast, good mast. When larger amounts of data are available in a unified three-point-scale database, they can be used to test hypotheses about past masting frequencies, the driving forces of masting or regional masting patterns.

KSC-2009-1003

NASA Image and Video Library

2009-01-02

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane completes construction of one of the towers in the new lightning protection system for the Constellation Program and Ares/Orion launches. Each of the three new lightning towers will be 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Troy Cryder

KSC-2009-1299

NASA Image and Video Library

2009-01-22

CAPE CANAVERAL, Fla. – Progress is being made on construction of the new lightning towers on Launch Pad 39B at NASA's Kennedy Space Center in Florida. New sections are being added with the help of a giant crane. Three new lightning towers on the pad will be 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Photo credit: NASA/Kim Shiflett

A first course in optimum design of yacht sails

NASA Astrophysics Data System (ADS)

Sugimoto, Takeshi

1993-03-01

The optimum sail geometry is analytically obtained for the case of maximizing the thrust under equality and inequality constraints on the lift and the heeling moment. A single mainsail is assumed to be set close-hauled in uniform wind and upright on the flat sea surface. The governing parameters are the mast height and the gap between the sail foot and the sea surface. The lifting line theory is applied to analyze the aerodynamic forces acting on a sail. The design method consists of the variational principle and a feasibility study. Almost triangular sails are found to be optimum. Their advantages are discussed.

KSC-2009-1329

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – In the rosy dawn light, construction of the towers on Launch Pad 39B at NASA's Kennedy Space Center in Florida continues on the new lightning protection system for the Constellation Program and Ares/Orion launches. Each of the three new lightning towers will be 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009.

KSC-2009-1328

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – In the rosy dawn light, construction of the towers on Launch Pad 39B at NASA's Kennedy Space Center in Florida continues on the new lightning protection system for the Constellation Program and Ares/Orion launches. Each of the three new lightning towers will be 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009.

46. BASE OF UMBILICAL MAST FROM UMBILICAL MAST TRENCH. ERECTION ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

46. BASE OF UMBILICAL MAST FROM UMBILICAL MAST TRENCH. ERECTION AND RETRACTION CYLINDERS BETWEEN MAST AND TRENCH WALL. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Mast Cells Produce a Unique Chondroitin Sulfate Epitope.

PubMed

Farrugia, Brooke L; Whitelock, John M; O'Grady, Robert; Caterson, Bruce; Lord, Megan S

2016-02-01

The granules of mast cells contain a myriad of mediators that are stored and protected by the sulfated glycosaminoglycan (GAG) chains that decorate proteoglycans. Whereas heparin is the GAG predominantly associated with mast cells, mast cell proteoglycans are also decorated with heparan sulfate and chondroitin sulfate (CS). This study investigated a unique CS structure produced by mast cells that was detected with the antibody clone 2B6 in the absence of chondroitinase ABC digestion. Mast cells in rodent tissue sections were characterized using toluidine blue, Leder stain and the presence of mast cell tryptase. The novel CS epitope was identified in rodent tissue sections and localized to cells that were morphologically similar to cells chemically identified as mast cells. The rodent mast cell-like line RBL-2H3 was also shown to express the novel CS epitope. This epitope co-localized with multiple CS proteoglycans in both rodent tissue and RBL-2H3 cultured cells. These findings suggest that the novel CS epitope that decorates mast cell proteoglycans may play a role in the way these chains are structured in mast cells. © 2016 The Histochemical Society.

Foxp3+ Regulatory T Cells Delay Expulsion of Intestinal Nematodes by Suppression of IL-9-Driven Mast Cell Activation in BALB/c but Not in C57BL/6 Mice

PubMed Central

Brenz, Yannick; Eschbach, Marie-Luise; Hartmann, Wiebke; Haben, Irma; Sparwasser, Tim; Huehn, Jochen; Kühl, Anja; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Breloer, Minka

2014-01-01

Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection. Here we report a different impact of Foxp3+ regulatory T cells (Treg) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice. Infection with Strongyloides ratti induced Treg expansion with similar kinetics and phenotype in both strains. Strikingly, Treg depletion reduced parasite burden selectively in BALB/c but not in C57BL/6 mice. Treg function was apparent in both strains as Treg depletion increased nematode-specific humoral and cellular Th2 response in BALB/c and C57BL/6 mice to the same extent. Improved resistance in Treg-depleted BALB/c mice was accompanied by increased production of IL-9 and accelerated degranulation of mast cells. In contrast, IL-9 production was not significantly elevated and kinetics of mast cell degranulation were unaffected by Treg depletion in C57BL/6 mice. By in vivo neutralization, we demonstrate that increased IL-9 production during the first days of infection caused accelerated mast cell degranulation and rapid expulsion of S. ratti adults from the small intestine of Treg-depleted BALB/c mice. In genetically mast cell-deficient (Cpa3-Cre) BALB/c mice, Treg depletion still resulted in increased IL-9 production but resistance to S. ratti infection was lost, suggesting that IL-9-driven mast cell activation mediated accelerated expulsion of S. ratti in Treg-depleted BALB/c mice. This IL-9-driven mast cell degranulation is a central mechanism of S. ratti expulsion in both, BALB/c and C57BL/6 mice, because IL-9 injection reduced and IL-9 neutralization increased parasite burden in the presence of Treg in both strains. Therefore our results suggest that Foxp3+ Treg suppress sufficient IL-9 production for subsequent mast cell degranulation during S. ratti infection in a non-redundant manner in BALB/c mice, whereas additional regulatory pathways are functional in Treg-depleted C57BL/6 mice. PMID:24516385

Foxp3⁺ regulatory T cells delay expulsion of intestinal nematodes by suppression of IL-9-driven mast cell activation in BALB/c but not in C57BL/6 mice.

PubMed

Blankenhaus, Birte; Reitz, Martina; Brenz, Yannick; Eschbach, Marie-Luise; Hartmann, Wiebke; Haben, Irma; Sparwasser, Tim; Huehn, Jochen; Kühl, Anja; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Breloer, Minka

2014-02-01

Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection. Here we report a different impact of Foxp3⁺ regulatory T cells (Treg) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice. Infection with Strongyloides ratti induced Treg expansion with similar kinetics and phenotype in both strains. Strikingly, Treg depletion reduced parasite burden selectively in BALB/c but not in C57BL/6 mice. Treg function was apparent in both strains as Treg depletion increased nematode-specific humoral and cellular Th2 response in BALB/c and C57BL/6 mice to the same extent. Improved resistance in Treg-depleted BALB/c mice was accompanied by increased production of IL-9 and accelerated degranulation of mast cells. In contrast, IL-9 production was not significantly elevated and kinetics of mast cell degranulation were unaffected by Treg depletion in C57BL/6 mice. By in vivo neutralization, we demonstrate that increased IL-9 production during the first days of infection caused accelerated mast cell degranulation and rapid expulsion of S. ratti adults from the small intestine of Treg-depleted BALB/c mice. In genetically mast cell-deficient (Cpa3-Cre) BALB/c mice, Treg depletion still resulted in increased IL-9 production but resistance to S. ratti infection was lost, suggesting that IL-9-driven mast cell activation mediated accelerated expulsion of S. ratti in Treg-depleted BALB/c mice. This IL-9-driven mast cell degranulation is a central mechanism of S. ratti expulsion in both, BALB/c and C57BL/6 mice, because IL-9 injection reduced and IL-9 neutralization increased parasite burden in the presence of Treg in both strains. Therefore our results suggest that Foxp3⁺ Treg suppress sufficient IL-9 production for subsequent mast cell degranulation during S. ratti infection in a non-redundant manner in BALB/c mice, whereas additional regulatory pathways are functional in Treg-depleted C57BL/6 mice.

44. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM SOUTHWEST. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

44. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM SOUTHWEST. DOORS FOR THE UMBILICAL MAST TRENCH RAISED FOR MAINTENANCE POSITION OF 10 DEGREES. LAUNCHER IS RIGHT OF MAST; RAILS PARALLEL TO MAST. CONTROL PANELS LEFT TO RIGHT: ELECTRICAL PANEL, COMMUNICATIONS PANEL, AND MAST CONTROL PANEL. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Mast importance, production, and management

Treesearch

Harmon P., Jr. Weeks

1989-01-01

Mast is a broad term that refers to the various nuts and fruits produced by woody plants. It is usually subdivided into hard mast (nuts) and soft mast (fleshy fruits). Forest tree and shrub mast is an important seasonal food for many forest wildlife species.

IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice.

PubMed

Polukort, Stephanie H; Rovatti, Jeffrey; Carlson, Logan; Thompson, Chelsea; Ser-Dolansky, Jennifer; Kinney, Shannon R M; Schneider, Sallie S; Mathias, Clinton B

2016-06-15

IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. In this study, we demonstrate a novel role for IL-10 in promoting mast cell expansion and the development of IgE-mediated food allergy. Oral OVA challenge in sensitized BALB/c mice resulted in a robust intestinal mast cell response accompanied by allergic diarrhea, mast cell activation, and a predominance of Th2 cytokines, including enhanced IL-10 expression. In contrast, the development of intestinal anaphylaxis, including diarrhea, mast cell activation, and Th2 cytokine production, was significantly attenuated in IL-10(-/-) mice compared with wild-type (WT) controls. IL-10 also directly promoted the expansion, survival, and activation of mast cells; increased FcεRI expression on mast cells; and enhanced the production of mast cell cytokines. IL-10(-/-) mast cells had reduced functional capacity, which could be restored by exogenous IL-10. Similarly, attenuated passive anaphylaxis in IL-10(-/-) mice could be restored by IL-10 administration. The adoptive transfer of WT mast cells restored allergic symptoms in IL-10(-/-) mice, suggesting that the attenuated phenotype observed in these animals is due to a deficiency in IL-10-responding mast cells. Lastly, transfer of WT CD4 T cells also restored allergic diarrhea and intestinal mast cell numbers in IL-10(-/-) mice, suggesting that the regulation of IL-10-mediated intestinal mast cell expansion is T cell dependent. Our observations demonstrate a critical role for IL-10 in driving mucosal mast cell expansion and activation, suggesting that, in its absence, mast cell function is impaired, leading to attenuated food allergy symptoms. Copyright © 2016 by The American Association of Immunologists, Inc.

Relationship between Numerous Mast Cells and Early Follicular Development in Neonatal MRL/MpJ Mouse Ovaries

PubMed Central

Nakamura, Teppei; Otsuka, Saori; Ichii, Osamu; Sakata, Yuko; Nagasaki, Ken-Ichi; Hashimoto, Yoshiharu; Kon, Yasuhiro

2013-01-01

In the neonatal mouse ovary, clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. During this period, we found numerous mast cells in the ovary of MRL/MpJ mice and investigated their appearance and morphology with follicular development. The ovarian mast cells, which were already present at postnatal day 0, tended to localize adjacent to the surface epithelium. Among 11 different mouse strains, MRL/MpJ mice possessed the greatest number of ovarian mast cells. Ovarian mast cells were also found in DBA/1, BALB/c, NZW, and DBA/2 mice but rarely in C57BL/6, NZB, AKR, C3H/He, CBA, and ICR mice. The ovarian mast cells expressed connective tissue mast cell markers, although mast cells around the surface epithelium also expressed a mucosal mast cell marker in MRL/MpJ mice. Some ovarian mast cells migrated into the oocyte nests and directly contacted the compressed and degenerated oocytes. In MRL/MpJ mice, the number of oocytes in the nest was significantly lower than in the other strains, and the number of oocytes showed a positive correlation with the number of ovarian mast cells. The gene expression of a mast cell marker also correlated with the expression of an oocyte nest marker, suggesting a link between the appearance of ovarian ? 4mast cells and early follicular development. Furthermore, the expression of follicle developmental markers was significantly higher in MRL/MpJ mice than in C57BL/6 mice. These results indicate that the appearance of ovarian mast cells is a unique phenotype of neonatal MRL/MpJ mice, and that ovarian mast cells participate in early follicular development, especially nest breakdown. PMID:24124609

The emerging role of mast cells in liver disease.

PubMed

Jarido, Veronica; Kennedy, Lindsey; Hargrove, Laura; Demieville, Jennifer; Thomson, Joanne; Stephenson, Kristen; Francis, Heather

2017-08-01

The depth of our knowledge regarding mast cells has widened exponentially in the last 20 years. Once thought to be only important for allergy-mediated events, mast cells are now recognized to be important regulators of a number of pathological processes. The revelation that mast cells can influence organs, tissues, and cells has increased interest in mast cell research during liver disease. The purpose of this review is to refresh the reader's knowledge of the development, type, and location of mast cells and to review recent work that demonstrates the role of hepatic mast cells during diseased states. This review focuses primarily on liver diseases and mast cells during autoimmune disease, hepatitis, fatty liver disease, liver cancer, and aging in the liver. Overall, these studies demonstrate the potential role of mast cells in disease progression.

Infiltrating mast cells enhance benign prostatic hyperplasia through IL-6/STAT3/Cyclin D1 signals

PubMed Central

Ou, Zhenyu; He, Yao; Qi, Lin; Zu, Xiongbin; Wu, Longxiang; Cao, Zhenzhen; Li, Yuan; Liu, Longfei; Dube, Daud Athanasius; Wang, Zhi; Wang, Long

2017-01-01

Early evidences have showed that mast cells could infiltrate into benign prostatic hyperplasia (BPH) tissues, but the exact role of mast cells in BPH development remains unclear. In this study, we identified more mast cells existing in human BPH tissues compared with that in the normal prostate. In the in vitro co-culture system, BPH-1 prostate cells promoted activation and migration of mast cells, and mast cells conversely stimulated BPH-1 cells proliferation significantly. Molecular analysis demonstrated that mast cell-derived interleukin 6 (IL-6) could activate STAT3/Cyclin D1 signals in BPH-1 cells. Blocking IL-6 or STAT3 partially reverse the capacity of mast cells to enhance BPH-1 cell proliferation. Our findings suggest that infiltrating mast cells in BPH tissues could promote BPH development via IL-6/STAT3/Cyclin D1 signals. Therefore, targeting infiltrating mast cells may improve the therapeutic effect of BPH. PMID:28938626

Masting promotes individual- and population-level reproduction by increasing pollination efficiency.

PubMed

Moreira, Xoaquín; Abdala-Roberts, Luis; Linhart, Yan B; Mooney, Kailen A

2014-04-01

Masting is a reproductive strategy defined as the intermittent and synchronized production of large seed crops by a plant population. The pollination efficiency hypothesis proposes that masting increases pollination success in plants. Despite its general appeal, no previous studies have used long-term data together with population- and individual-level analyses to assess pollination efficiency between mast and non-mast events. Here we rigorously tested the pollination efficiency hypothesis in ponderosa pine (Pinus ponderosa), a long-lived monoecious, wind-pollinated species, using a data set on 217 trees monitored annually for 20 years. Relative investment in male and female function by individual trees did not vary between mast and non-mast years. At both the population and individual level, the rate of production of mature female cones relative to male strobili production was higher in mast than non-mast years, consistent with the predicted benefit of reproductive synchrony on reproductive success. In addition, at the individual level we found a higher conversion of unfertilized female conelets into mature female cones during a mast year compared to a non-mast year. Collectively, parallel results at the population and individual tree level provide robust evidence for the ecological, and potentially also evolutionary, benefits of masting through increased pollination efficiency.

Spatial patterns and broad-scale weather cues of beech mast seeding in Europe.

PubMed

Vacchiano, Giorgio; Hacket-Pain, Andrew; Turco, Marco; Motta, Renzo; Maringer, Janet; Conedera, Marco; Drobyshev, Igor; Ascoli, Davide

2017-07-01

Mast seeding is a crucial population process in many tree species, but its spatio-temporal patterns and drivers at the continental scale remain unknown . Using a large dataset (8000 masting observations across Europe for years 1950-2014) we analysed the spatial pattern of masting across the entire geographical range of European beech, how it is influenced by precipitation, temperature and drought, and the temporal and spatial stability of masting-weather correlations. Beech masting exhibited a general distance-dependent synchronicity and a pattern structured in three broad geographical groups consistent with continental climate regimes. Spearman's correlations and logistic regression revealed a general pattern of beech masting correlating negatively with temperature in the summer 2 yr before masting, and positively with summer temperature 1 yr before masting (i.e. 2T model). The temperature difference between the two previous summers (DeltaT model) was also a good predictor. Moving correlation analysis applied to the longest eight chronologies (74-114 yr) revealed stable correlations between temperature and masting, confirming consistency in weather cues across space and time. These results confirm widespread dependency of masting on temperature and lend robustness to the attempts to reconstruct and predict mast years using temperature data. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment

PubMed Central

Wang, Shan; Li, Linmei; Shi, Renren; Liu, Xueting; Zhang, Junyan; Zou, Zehong; Hao, Zhuofang; Tao, Ailin

2016-01-01

The association of colitis with colorectal cancer has become increasingly clear with mast cells being identified as important inflammatory cells in the process. In view of the relationship between mast cells and cancer, we studied the effect and mechanisms of mast cells in the development of colon cancer. Functional and mechanistic insights were gained from ex vivo and in vivo studies of cell interactions between mast cells and CT26 cells. Further evidence was reversely obtained in studies of mast cell targeted Fcε-PE40 chimeric toxin. Experiments revealed mast cells could induce colon tumor cell proliferation and invasion. Cancer progression was found to be related to the density of mast cells in colonic submucosa. The activation of MAPK, Rho-GTPase, and STAT pathways in colon cancer cells was triggered by mast cells during cell-to-cell interaction. Lastly, using an Fcε-PE40 chimeric toxin we constructed, we confirmed the promoting effect of mast cells in development of colon cancer. Mast cells are a promoting factor of colon cancer and thus also a potential therapeutic target. The Fcε-PE40 chimeric toxin targeting mast cells could effectively prevent colon cancer in vitro and in vivo. Consequently, these data may demonstrate a novel immunotherapeutic approach for the treatment of tumors. PMID:26978404

Increased number of mast cells in the dermis in actinic keratosis lesions effectively treated with imiquimod.

PubMed

Oyama, Satomi; Funasaka, Yoko; Tsuchiya, Shin-Ichi; Kawana, Seiji; Saeki, Hidehisa

2017-08-01

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo-network ("strawberry") pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki-67-positive proliferative cells in the epidermis was decreased and that of CD117-positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod. © 2017 Japanese Dermatological Association.

Effects of Bidens pilosa L. var. radiata SCHERFF treated with enzyme on histamine-induced contraction of guinea pig ileum and on histamine release from mast cells.

PubMed

Matsumoto, Takayuki; Horiuchi, Masako; Kamata, Katsuo; Seyama, Yoshiyuki

2009-06-01

The medical mechanism against type I allergies is to block the release or production of chemical mediators from mast cells or to block the H(1)-receptor signaling. We previously reported that the anti-allergic action of the dry powder from Bidens pilosa L. var. radiata SCHERFF treated with the enzyme cellulosine (eMMBP) was dependent on the inhibition of histamine release from mast cells. Here, we investigate that the effect of fractions in eMMBP on the histamine-induced contraction in guinea pig ileum and on the release of histamine in rat peritoneal mast cells. The histamine-induced contraction in guinea pig ileum is dose-dependently inhibited by ketotifen, an antagonist of H(1)-receptor. Fractions contained caffeic acid, caffeoylquinic acid and fractions contained flavonoids such as hyperin and isoquercitrin in eMMBP inhibit histamine release from mast cells, but only flavonoids such as hyperin, isoquercitrin and rutin suppress the histamine-induced contraction in guinea pig ileum. Moreover, the histamine-induced contraction was not affected by caffeic acid, however, such contraction was significantly inhibited by rutin. These results suggest that the primary antagonists of H(1)- receptor are different from the components in eMMBP that inhibit histamine release, and that these components participate in the anti-allergic activity of eMMBP.

Radiofrequency radiation injures trees around mobile phone base stations.

PubMed

Waldmann-Selsam, Cornelia; Balmori-de la Puente, Alfonso; Breunig, Helmut; Balmori, Alfonso

2016-12-01

In the last two decades, the deployment of phone masts around the world has taken place and, for many years, there has been a discussion in the scientific community about the possible environmental impact from mobile phone base stations. Trees have several advantages over animals as experimental subjects and the aim of this study was to verify whether there is a connection between unusual (generally unilateral) tree damage and radiofrequency exposure. To achieve this, a detailed long-term (2006-2015) field monitoring study was performed in the cities of Bamberg and Hallstadt (Germany). During monitoring, observations and photographic recordings of unusual or unexplainable tree damage were taken, alongside the measurement of electromagnetic radiation. In 2015 measurements of RF-EMF (Radiofrequency Electromagnetic Fields) were carried out. A polygon spanning both cities was chosen as the study site, where 144 measurements of the radiofrequency of electromagnetic fields were taken at a height of 1.5m in streets and parks at different locations. By interpolation of the 144 measurement points, we were able to compile an electromagnetic map of the power flux density in Bamberg and Hallstadt. We selected 60 damaged trees, in addition to 30 randomly selected trees and 30 trees in low radiation areas (n=120) in this polygon. The measurements of all trees revealed significant differences between the damaged side facing a phone mast and the opposite side, as well as differences between the exposed side of damaged trees and all other groups of trees in both sides. Thus, we found that side differences in measured values of power flux density corresponded to side differences in damage. The 30 selected trees in low radiation areas (no visual contact to any phone mast and power flux density under 50μW/m 2 ) showed no damage. Statistical analysis demonstrated that electromagnetic radiation from mobile phone masts is harmful for trees. These results are consistent with the fact that damage afflicted on trees by mobile phone towers usually start on one side, extending to the whole tree over time. Copyright © 2016 Elsevier B.V. All rights reserved.

Tradeoffs in basal area growth and reproduction shift over the lifetime of a long-lived tropical species.

PubMed

Staudhammer, Christina L; Wadt, Lúcia H O; Kainer, Karen A

2013-09-01

Understanding of the extent to which reproductive costs drive growth largely derives from reproductively mature temperate trees in masting and non-masting years. We modeled basal area increment (BAI) and explored current growth-reproduction tradeoffs and changes in such allocation over the life span of a long-lived, non-masting tropical tree. We integrated rainfall and soil variables with data from 190 Bertholletia excelsa trees of different diameter at breast height (DBH) sizes, crown characteristics, and liana loads, quantifying BAI and reproductive output over 4 and 6 years, respectively. While rainfall explains BAI in all models, regardless of DBH class or ontogenic stage, light (based on canopy position and crown form) is most critical in the juvenile (5 cm ≤ DBH < 50 cm) phase. Suppressed trees are only present as juveniles and grow ten times slower (1.45 ± 2.73 m(2) year(-1)) than trees in dominant and co-dominant positions (13.25 ± 0.82 and 12.90 ± 1.35 m(2) year(-1), respectively). Additionally, few juvenile trees are reproductive, and those that are, demonstrate reduced growth, as do reproductive trees in the next 50 to 100 cm DBH class, suggesting growth-reproduction tradeoffs. Upon reaching the canopy, however, and attaining a sizeable girth, this pattern gradually shifts to one where BAI and reproduction are influenced independently by variables such as liana load, crown size and soil properties. At this stage, BAI is largely unaffected by fruit production levels. Thus, while growth-reproduction tradeoffs clearly exist during early life stages, effects of reproductive allocation diminish as B. excelsa increases in size and maturity.

Comparison of shipborne GNSS-derived precipitable water vapor with radiosonde in the western North Pacific and in the seas adjacent to Japan

NASA Astrophysics Data System (ADS)

Shoji, Yoshinori; Sato, Kazutoshi; Yabuki, Masanori; Tsuda, Toshitaka

2017-11-01

We installed two global navigation satellite system (GNSS) antennas on a research vessel, the RYOFU MARU of the Japan Meteorological Agency, and conducted experimental observations to assess the GNSS-derived precipitable water vapor (PWV) from October 19, 2016, to August 6, 2017. One antenna was set on the mast (MAST), while another antenna was set on the upper deck (DECK). The GNSS analysis was conducted using the precise point positioning procedure with a real-time GNSS orbit. A quality control (QC) procedure based on the amount of zenith tropospheric delay (ZTD) time variation was proposed. After the QC was applied, the retrieved PWVs were compared to 77 radiosonde observations. The PWVs of MAST agreed with the radiosonde observations with a 1.7 mm root mean square (RMS) difference, a - 0.7-mm bias, and 3.6% rejection rate, while that of DECK showed a 3.2, - 0.8 mm, and 15.7%. The larger RMS and higher rejection rate of DECK imply a stronger multi-path effect on the deck. The differences in the GNSS PWV versus radiosonde observations were compared to the atmospheric delay, the estimated altitude of the GNSS antenna, the vessel's moving speed, the wind speed, and the wave height. The atmospheric delay and GNSS antenna altitude showed moderate correlation with the differences. The results suggest the kinematic PPP's potential for practical water vapor monitoring over oceans worldwide. At the same time, from the growing negative biases with the PWV value and with estimated antenna altitude, it could be inferred that the difficulty grows in separating the signal delay from the vertical coordinate under high-humidity conditions.[Figure not available: see fulltext.

Self-anchoring mast for deploying a high-speed submersible mixer in a tank

DOEpatents

Cato, Jr., Joseph E.; Shearer, Paul M [Aiken, SC; Rodwell, Philip O [Evans, GA

2004-10-12

A self-anchoring mast for deploying a high-speed submersible mixer in a tank includes operably connected first and second mast members (20, 22) and a foot member 46 operably connected to the second mast member for supporting the mast in a tank. The second mast member includes a track (36, 38) for slidably receiving a bearing of the mixer to change the orientation of the mixer in the tank.

New developments in mast cell biology

PubMed Central

Kalesnikoff, Janet; Galli, Stephen J.

2010-01-01

Mast cells can function as effector and immunoregulatory cells in IgE-associated allergic disorders, as well as in certain innate and adaptive immune responses. This review will focus on exciting new developments in the field of mast cell biology published within the last year. It will highlight advances in the understanding of FcεRI-mediated signaling and mast cell activation events, as well as in the use of genetic models to study mast cell function in vivo. Finally, we will discuss newly identified roles of mast cells or individual mast cell products, such as proteases and IL-10, in host defense, cardiovascular disease and tumor biology, and in settings in which mast cells have anti-inflammatory or immunosuppressive functions. PMID:18936782

Loss of histochemical identity in mast cells lacking carboxypeptidase A.

PubMed

Feyerabend, Thorsten B; Hausser, Heinz; Tietz, Annette; Blum, Carmen; Hellman, Lars; Straus, Anita H; Takahashi, Hélio K; Morgan, Ellen S; Dvorak, Ann M; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2005-07-01

Mast cell carboxypeptidase A (Mc-cpa) is a highly conserved secretory granule protease. The onset of expression in mast cell progenitors and lineage specificity suggest an important role for Mc-cpa in mast cells. To address the function of Mc-cpa, we generated Mc-cpa-null mice. Mc-cpa-/- mast cells lacked carboxypeptidase activity, revealing that Mc-cpa is a nonredundant enzyme. While Mc-cpa-/- peritoneal mast cells were ultrastructurally normal and synthesized normal amounts of heparin, they displayed striking histochemical and biochemical hallmarks of immature mast cells. Wild-type peritoneal mast cells had a mature phenotype characterized by differential histochemical staining with proteoglycan-reactive dyes (cells do not stain with alcian blue but stain with safranin and with berberine) and a high side scatter to forward scatter ratio by flow cytometry and were detergent resistant. In contrast, Mc-cpa-/- peritoneal mast cells, like immature bone marrow-derived cultured mast cells, stained with alcian blue normally or weakly and either did not stain with safranin and berberine or stained weakly, had a low side scatter to forward scatter ratio, and were detergent sensitive. This phenotype was partially ameliorated with age. Thus, histochemistry and flow cytometry, commonly used to measure mast cell maturation, deviated from morphology in Mc-cpa-/- mice. The Mc-cpa-/- mast cell phenotype was not associated with defects in degranulation in vitro or passive cutaneous anaphylaxis in vivo. Collectively, Mc-cpa plays a crucial role for the generation of phenotypically mature mast cells.

Loss of Histochemical Identity in Mast Cells Lacking Carboxypeptidase A

PubMed Central

Feyerabend, Thorsten B.; Hausser, Heinz; Tietz, Annette; Blum, Carmen; Hellman, Lars; Straus, Anita H.; Takahashi, Hélio K.; Morgan, Ellen S.; Dvorak, Ann M.; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2005-01-01

Mast cell carboxypeptidase A (Mc-cpa) is a highly conserved secretory granule protease. The onset of expression in mast cell progenitors and lineage specificity suggest an important role for Mc-cpa in mast cells. To address the function of Mc-cpa, we generated Mc-cpa-null mice. Mc-cpa−/− mast cells lacked carboxypeptidase activity, revealing that Mc-cpa is a nonredundant enzyme. While Mc-cpa−/− peritoneal mast cells were ultrastructurally normal and synthesized normal amounts of heparin, they displayed striking histochemical and biochemical hallmarks of immature mast cells. Wild-type peritoneal mast cells had a mature phenotype characterized by differential histochemical staining with proteoglycan-reactive dyes (cells do not stain with alcian blue but stain with safranin and with berberine) and a high side scatter to forward scatter ratio by flow cytometry and were detergent resistant. In contrast, Mc-cpa−/− peritoneal mast cells, like immature bone marrow-derived cultured mast cells, stained with alcian blue normally or weakly and either did not stain with safranin and berberine or stained weakly, had a low side scatter to forward scatter ratio, and were detergent sensitive. This phenotype was partially ameliorated with age. Thus, histochemistry and flow cytometry, commonly used to measure mast cell maturation, deviated from morphology in Mc-cpa−/− mice. The Mc-cpa−/− mast cell phenotype was not associated with defects in degranulation in vitro or passive cutaneous anaphylaxis in vivo. Collectively, Mc-cpa plays a crucial role for the generation of phenotypically mature mast cells. PMID:15988029

Efficacy of long-term intralesional triamcinolone in Morbihan's disease and its possible association with mast cell infiltration.

PubMed

Tsiogka, Aikaterini; Koller, Josef

2018-04-23

Morbihan's disease is characterized by chronic persistent facial edema of the upper half of the face, absence of typical diagnostic findings, and refractoriness to treatment. A 44-year-old man was diagnosed with Morbihan's disease based on clinical signs and histopathology, which showed dermal edema in upper dermis, discrete lymphocytic infiltrate without granulomatous reaction, and mast cell infiltration. After long-term therapy with intralesional triamcinolone a remarkable objective and subjective clinical response was observed. Reported cases of Morbihan's disease are reviewed, with respect to their treatment and histopathological findings. Mast cell infiltration has been observed on histopathology in most patients who responded to intralesional triamcinolone, suggesting a possible marker of response. The long-lasting response seen in our case indicates the efficacy of intralesional triamcinolone in this rare condition. © 2018 Wiley Periodicals, Inc.

Induction of mast cell accumulation by chymase via an enzymatic activity- and intercellular adhesion molecule-1-dependent mechanism.

PubMed

Zhang, Huiyun; Wang, Junling; Wang, Ling; Zhan, Mengmeng; Li, Shigang; Fang, Zeman; Xu, Ciyan; Zheng, Yanshan; He, Shaoheng

2018-02-01

Chymase is a unique, abundant secretory product of mast cells and a potent chemoattractant for eosinophils, monocytes and neutrophils, but little is known of its influence on mast cell accumulation. A mouse peritoneal inflammation model, cell migration assay and flowcytometry analysis, were used to investigate the role of chymase in recruiting mast cells. Chymase increased, by up to 5.4-fold, mast cell numbers in mouse peritoneum. Inhibitors of chymase, heat-inactivation of the enzyme, sodium cromoglycate and terfenadine, and pretreatment of mice with anti-intercellular adhesion molecule 1, anti-L-selectin, anti-CD11a and anti-CD18 antibodies dramatically diminished the chymase-induced increase in mast cell accumulation. These findings indicate that this effect of chymase is dependent on its enzymatic activity and activation of adhesion molecules. In addition, chymase provoked a significant increase in 5-HT and eotaxin release (up to 1.8- and 2.2-fold, respectively) in mouse peritoneum. Since 5-HT, eotaxin and RANTES can induce marked mast cell accumulation, these indirect mechanisms may also contribute to chymase-induced mast cell accumulation. Moreover, chymase increased the trans-endothelium migration of mast cells in vitro indicating it also acts as a chemoattractant. The finding that mast cells accumulate in response to chymase implies further that chymase is a major pro-inflammatory mediator of mast cells. This effect of chymase, a major product of mast cell granules, suggests a novel self-amplification mechanism for mast cell accumulation in allergic inflammation. Mast cell stabilizers and inhibitors of chymase may have potential as a treatment of allergic disorders. © 2017 The British Pharmacological Society.

Mechanisms mediating nitroglycerin-induced delayed-onset hyperalgesia in the rat.

PubMed

Ferrari, L F; Levine, J D; Green, P G

2016-03-11

Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN's very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ∼ 30 min in male and ∼ 45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed-onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggests potential novel risk factors and targets for the treatment of migraine. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Synthesis and anti-inflammatory effect of chalcones and related compounds.

PubMed

Hsieh, H K; Lee, T H; Wang, J P; Wang, J J; Lin, C N

1998-01-01

Mast cell and neutrophil degranulations are the important players in inflammatory disorders. Combined with potent inhibition of chemical mediators released from mast cells and neutrophil degranulations, it could be a promising anti-inflammatory agent. 2',5'-Dihydroxychalcone has been reported as a potent chemical mediator and cyclooxygenase inhibitor. In an effort to continually develop potent anti-inflammatory agents, a novel series of chalcone, 2'- and 3'-hydroxychalcones, 2',5'-dihydroxychalcones and flavanones were continually synthesized to evaluate their inhibitory effects on the activation of mast cells and neutrophils and the inhibitory effect on phlogist-induced hind-paw edema in mice. A series of chalcones and related compounds were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde and the anti-inflammatory activities of these synthetic compounds were studied on inhibitory effects on the activation of mast cells and neutrophils. Some chalcones showed strong inhibitory effects on the release of beta-glucuronidase and histamine from rat peritoneal mast cells stimulated with compound 48/80. Almost all chalcones and 4'-hydroxyflavanone exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). Some chalcones showed potent inhibitory effects on superoxide formation of rat neutrophils stimulated with fMLP/cytochalasin B (CB) or phorbol myristate acetate (PMA). 2',3-Dihydroxy-, 2',5'-dihydroxy-4-chloro-, and 2',5'-dihydroxychalcone showed remarkable inhibitory effects on hind-paw edema induced by polymyxin B in normal as well as in adrenalectomized mice. These results indicated that the anti-inflammatory effects of these compounds were mediated, at least partly, through the suppression of chemical mediators released from mast cells and neutrophils.

Tanshinone IIA suppresses FcεRI-mediated mast cell signaling and anaphylaxis by activation of the Sirt1/LKB1/AMPK pathway.

PubMed

Li, Xian; Park, Soon Jin; Jin, Fansi; Deng, Yifeng; Yang, Ju Hye; Chang, Jae-Hoon; Kim, Dong-Young; Kim, Jung-Ae; Lee, Youn Ju; Murakami, Makoto; Son, Kun Ho; Chang, Hyeun Wook

2018-06-01

AMP-activated protein kinase (AMPK) and its upstream mediators liver kinase B1 (LKB1) and sirtuin 1 (Sirt1) are generally known as key regulators of metabolism. We have recently reported that the AMPK pathway negatively regulates mast cell activation and anaphylaxis. Tanshinone IIA (Tan IIA), an active component of Salvia miltiorrhiza extract that is currently used for the treatment of cardiovascular and cerebrovascular diseases, shows anti-diabetic activity and improves insulin resistance in db/db mice through activation of AMPK. The aim of this study was to evaluate the anti-allergic activity of Tan IIA in vivo and to investigate the underlying mechanism in vitro in the context of AMPK signaling. The anti-allergic effect of Tan IIA was evaluated using mouse bone marrow-derived mast cells (BMMCs) from AMPKα2 -/- or Sirt1 -/- mice, or BMMCs transfected with siRNAs specific for AMPKα2, LKB1, or Sirt1. AMPKα2 -/- and Sirt1 -/- mice were used to confirm the anti-allergic effect of Tan IIA in anaphylaxis in vivo. Tan IIA dose-dependently inhibited FcεRI-mediated degranulation and production of eicosanoids and cytokines in BMMCs. These inhibitory effects were diminished by siRNA-mediated knockdown or genetic deletion of AMPKα2 or Sirt1. Moreover, Tan IIA inhibited a mast cell-mediated local passive anaphylactic reaction in wild-type mice, but not in AMPKα2 -/- or Sirt1 -/- mice. In conclusion, Tan IIA suppresses FcεRI-mediated mast cell activation and anaphylaxis through activation of the inhibitory Sirt1-LKB1-AMPK pathway. Thus, Tan IIA may be useful as a new therapeutic agent for mast cell-mediated allergic diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Th17 cell-mediated immune responses promote mast cell proliferation by triggering stem cell factor in keratinocytes

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

Cho, Kyung-Ah; Park, Minhwa; Kim, Yu-Hee

Although mast cells are traditionally thought to function as effector cells in allergic responses, they have increasingly been recognized as important regulators of various immune responses. Mast cells mature locally; thus, tissue-specific influences are important for promoting mast cell accumulation and survival in the skin and the gastrointestinal tract. In this study, we determined the effects of keratinocytes on mast cell accumulation during Th17-mediated skin inflammation. We observed increases in dermal mast cells in imiquimod-induced psoriatic dermatitis in mice accompanied by the expression of epidermal stem cell factor (SCF), a critical mast cell growth factor. Similar to mouse epidermal keratinocytes,more » SCF was highly expressed in the human HaCaT keratinocyte cell line following stimulation with IL−17. Further, keratinocytes promoted mast cell proliferation following stimulation with IL−17 in vitro. However, the effects of keratinocytes on mast cells were significantly diminished in the presence of anti−CD117 (stem cell factor receptor) blocking antibodies. Taken together, our results revealed that the Th17-mediated inflammatory environment promotes mast cell accumulation through keratinocyte-derived SCF. - Highlights: • Psoriasis-like skin inflammation increase dermal mast cells. • Keratinocyte produce stem cell factor in psoriasis-like skin inflammation. • Keratinocyte promote mast cell proliferation by stem cell factor dependent manner.« less

Overview of MAST results

NASA Astrophysics Data System (ADS)

Chapman, I. T.; Adamek, J.; Akers, R. J.; Allan, S.; Appel, L.; Asunta, O.; Barnes, M.; Ben Ayed, N.; Bigelow, T.; Boeglin, W.; Bradley, J.; Brünner, J.; Cahyna, P.; Carr, M.; Caughman, J.; Cecconello, M.; Challis, C.; Chapman, S.; Chorley, J.; Colyer, G.; Conway, N.; Cooper, W. A.; Cox, M.; Crocker, N.; Crowley, B.; Cunningham, G.; Danilov, A.; Darrow, D.; Dendy, R.; Diallo, A.; Dickinson, D.; Diem, S.; Dorland, W.; Dudson, B.; Dunai, D.; Easy, L.; Elmore, S.; Field, A.; Fishpool, G.; Fox, M.; Fredrickson, E.; Freethy, S.; Garzotti, L.; Ghim, Y. C.; Gibson, K.; Graves, J.; Gurl, C.; Guttenfelder, W.; Ham, C.; Harrison, J.; Harting, D.; Havlickova, E.; Hawke, J.; Hawkes, N.; Hender, T.; Henderson, S.; Highcock, E.; Hillesheim, J.; Hnat, B.; Holgate, J.; Horacek, J.; Howard, J.; Huang, B.; Imada, K.; Jones, O.; Kaye, S.; Keeling, D.; Kirk, A.; Klimek, I.; Kocan, M.; Leggate, H.; Lilley, M.; Lipschultz, B.; Lisgo, S.; Liu, Y. Q.; Lloyd, B.; Lomanowski, B.; Lupelli, I.; Maddison, G.; Mailloux, J.; Martin, R.; McArdle, G.; McClements, K.; McMillan, B.; Meakins, A.; Meyer, H.; Michael, C.; Militello, F.; Milnes, J.; Morris, A. W.; Motojima, G.; Muir, D.; Nardon, E.; Naulin, V.; Naylor, G.; Nielsen, A.; O'Brien, M.; O'Gorman, T.; Ono, Y.; Oliver, H.; Pamela, S.; Pangione, L.; Parra, F.; Patel, A.; Peebles, W.; Peng, M.; Perez, R.; Pinches, S.; Piron, L.; Podesta, M.; Price, M.; Reinke, M.; Ren, Y.; Roach, C.; Robinson, J.; Romanelli, M.; Rozhansky, V.; Saarelma, S.; Sangaroon, S.; Saveliev, A.; Scannell, R.; Schekochihin, A.; Sharapov, S.; Sharples, R.; Shevchenko, V.; Silburn, S.; Simpson, J.; Storrs, J.; Takase, Y.; Tanabe, H.; Tanaka, H.; Taylor, D.; Taylor, G.; Thomas, D.; Thomas-Davies, N.; Thornton, A.; Turnyanskiy, M.; Valovic, M.; Vann, R.; Walkden, N.; Wilson, H.; van Wyk, F.; Yamada, T.; Zoletnik, S.; MAST; MAST Upgrade Teams

2015-10-01

The Mega Ampère Spherical Tokamak (MAST) programme is strongly focused on addressing key physics issues in preparation for operation of ITER as well as providing solutions for DEMO design choices. In this regard, MAST has provided key results in understanding and optimizing H-mode confinement, operating with smaller edge localized modes (ELMs), predicting and handling plasma exhaust and tailoring auxiliary current drive. In all cases, the high-resolution diagnostic capability on MAST is complemented by sophisticated numerical modelling to facilitate a deeper understanding. Mitigation of ELMs with resonant magnetic perturbations (RMPs) with toroidal mode number nRMP = 2, 3, 4, 6 has been demonstrated: at high and low collisionality; for the first ELM following the transition to high confinement operation; during the current ramp-up; and with rotating nRMP = 3 RMPs. nRMP = 4, 6 fields cause less rotation braking whilst the power to access H-mode is less with nRMP = 4 than nRMP = 3, 6. Refuelling with gas or pellets gives plasmas with mitigated ELMs and reduced peak heat flux at the same time as achieving good confinement. A synergy exists between pellet fuelling and RMPs, since mitigated ELMs remove fewer particles. Inter-ELM instabilities observed with Doppler backscattering are consistent with gyrokinetic simulations of micro-tearing modes in the pedestal. Meanwhile, ELM precursors have been strikingly observed with beam emission spectroscopy (BES) measurements. A scan in beta at the L-H transition shows that pedestal height scales strongly with core pressure. Gyro-Bohm normalized turbulent ion heat flux (as estimated from the BES data) is observed to decrease with increasing tilt of the turbulent eddies. Fast ion redistribution by energetic particle modes depends on density, and access to a quiescent domain with ‘classical’ fast ion transport is found above a critical density. Highly efficient electron Bernstein wave current drive (1 A W-1) has been achieved in solenoid-free start-up. A new proton detector has characterized escaping fusion products. Langmuir probes and a high-speed camera suggest filaments play a role in particle transport in the private flux region whilst coherence imaging has measured scrape-off layer (SOL) flows. BOUT++ simulations show that fluxes due to filaments are strongly dependent on resistivity and magnetic geometry of the SOL, with higher radial fluxes at higher resistivity. Finally, MAST Upgrade is due to begin operation in 2016 to support ITER preparation and importantly to operate with a Super-X divertor to test extended leg concepts for particle and power exhaust.

[Vulvar oedema revealing systemic mastocytosis].

PubMed

Deveza, E; Locatelli, F; Girardin, M; Valmary-Degano, S; Daguindau, E; Aubin, F; Humbert, P; Pelletier, F

2015-11-01

Systemic mastocytosis is characterised by abnormal proliferation of mast cells in various organs. We report an original case of systemic mastocytosis revealed by vulvar oedema. A 24-year-old patient was examined in the dermatology department for vulvar oedema appearing during sexual intercourse. She presented vasomotor dysfunction of the lower limbs, urticaria on the trunk on exertion, diarrhoea and bone pains. Laboratory tests showed serum tryptase of 29.7μg and plasma histamine at twice the normal value. Myelogram results showed infiltration by dysmorphic mast cells. Screening for c-kit D816V mutation was positive. Duodenal biopsies revealed mast-cell clusters with aggregation involving over 15 mast cells. CD2 staining was inconclusive and CD25 staining could not be done. Trabecular osteopenia was found, and we thus made a diagnosis of indolent systemic mastocytosis (ISM variant Ia) as per the WHO 2008 criteria. Symptomatic treatment was initiated (antiH1, H2, antileukotrienes) and clinical and laboratory follow-up was instituted. The cutaneous signs leading to diagnosis in this patient of systemic mastocytosis involving several organs were seemingly minimal signs associated with mastocyte degranulation. This is the third recorded case of mastocytosis revealed by vulvar oedema and the first case revealing systemic involvement. The two previously reported cases of vulvar oedema revealed cutaneous mastocytosis alone. Mastocytosis, whether systemic or cutaneous, must be included among the differential diagnoses considered in the presence of vulvar oedema. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Lightning Protection System for Space Shuttle

NASA Technical Reports Server (NTRS)

1977-01-01

The suitability and cost effectiveness of using a lightning mast for the shuttle service and access tower (SSAT) similar to the type used for the Apollo Soyuz Test Project (ASTP) mobile launcher (ML) was evaluated. Topics covered include: (1) ASTP launch damage to mast, mast supports, grounded overhead wires, and the instrumentation system; (2) modifications required to permit reusing the ASTP mast on the SSAT; (3) comparative costing factors per launch over a 10 year period in repetitive maintenance and refurbishment of the existing and modified masts, mast supports, grounded overhead wires, and ground instrumentation required to sustain mechanical and electrical integrity of the masts; (4) effects of blast testing samples of the ASTP ML type mast (corrosion and electrical flashover); (5) comparison of damages from ASTP launch and from blast testing.

Graphic representation of STS-99 orbiter during mission

NASA Image and Video Library

2000-02-04

JSC2000E01551 (January 2000) --- An "exploded" drawing depicts the Space Shuttle Endeavour and the Shuttle Radar Topography Mission (SRTM) mast, along with the pallet for SRTM and supportive antennae. The mast will be deployed and retracted by a motor-driven nut within the mast canister. This nut will pull the mast from its stowed configuration and allow it to unfold like an accordion. A crew member inside the shuttle will initiate the mast deployment, a chore which will take about 20 minutes. The mast also can be deployed manually during a contingency extravehicular activity (EVA) using a hand-held motor. The mast is 200 feet (60 meters) long.

Tissue-dependent differences in the asynchronous appearance of mast cells in normal mice and in congenic mast cell-deficient mice after infusion of normal bone marrow cells

PubMed Central

DU, T; FRIEND, D S; AUSTEN, K F; KATZ, H R

1996-01-01

The time courses of the appearance of tissue mast cells in six sites were compared in normal WBB6F1-+/+ mice (+/+) and in congenic mast cell-deficient WBB6F1-W/Wv mice (W/Wv) that received an intravenous infusion of bone marrow cells from +/+mice (BM→W/Wv). As assessed by morphometric analysis of Carnoy's solution-fixed, methylene blue-stained tissue sections, the density of mast cells in the stomach mucosa, stomach submucosa, and spleen of +/+ mice reached maximal levels by 8 weeks of age, whereas the density of mast cells in the skin, extraparenchymal airway walls, and lung parenchyma did not reach maximal levels until 18 weeks of age. When 8-week-old W/Wv mice were infused with 2×107 bone marrow cells from +/+ mice, mast cells appeared in the stomach mucosa and submucosa after 2.5 weeks, in the spleen and extraparenchymal airway walls after 5 weeks, and in the lung parenchyma after 10 weeks. Twenty weeks after bone marrow infusion, the mast cell densities in the spleen, stomach mucosa, and stomach submucosa were seven-, 13-, and five-fold greater, respectively, than those in age-matched +/+ mice, but were eight-, two-, and five-fold lower in the skin, extraparenchymal airway walls, and lung parenchyma, respectively. Thus, those tissues that in +/+ mice reached maximal mast cell densities earlier exhibited abnormally high mast cell densities in BM→W/Wv mice, and those that reached maximal mast cell densities later in +/+ mice had abnormally low mast cell densities in BM→W/Wv mice. Immunological and inflammatory responses are often compared in W/Wv and BM→W/Wv mice to assess mast cell dependency. Our results indicate that the capacity to restore a mast cell-dependent response in a particular tissue of the latter mice may relate to the local mast cell density and whether the immunological challenge activates mast cells only in that tissue or systematically with attendant widespread release of proinflammatory mediators. PMID:8565318

Lipid Rafts in Mast Cell Biology

PubMed Central

Silveira e Souza, Adriana Maria Mariano; Mazucato, Vivian Marino; Jamur, Maria Célia; Oliver, Constance

2011-01-01

Mast cells have long been recognized to have a direct and critical role in allergic and inflammatory reactions. In allergic diseases, these cells exert both local and systemic responses, including allergic rhinitis and anaphylaxis. Mast cell mediators are also related to many chronic inflammatory conditions. Besides the roles in pathological conditions, the biological functions of mast cells include roles in innate immunity, involvement in host defense mechanisms against parasites, immunomodulation of the immune system, tissue repair, and angiogenesis. Despite their growing significance in physiological and pathological conditions, much still remains to be learned about mast cell biology. This paper presents evidence that lipid rafts or raft components modulate many of the biological processes in mast cells, such as degranulation and endocytosis, play a role in mast cell development and recruitment, and contribute to the overall preservation of mast cell structure and organization. PMID:21490812

Ablation of human skin mast cells in situ by lysosomotropic agents.

PubMed

Hagforsen, Eva; Paivandy, Aida; Lampinen, Maria; Weström, Simone; Calounova, Gabriela; Melo, Fabio R; Rollman, Ola; Pejler, Gunnar

2015-07-01

Mast cells are known to have a detrimental impact on numerous types of inflammatory skin diseases such as contact dermatitis, atopic eczema and cutaneous mastocytosis. Regimens that dampen skin mast cell-mediated activities can thus offer an attractive therapeutic option under such circumstances. As mast cells are known to secrete a large array of potentially pathogenic compounds, both from preformed stores in secretory lysosomes (granules) and after de novo synthesis, mere inhibition of degranulation or interference with individual mast cell mediators may not be sufficient to provide an effective blockade of harmful mast cell activities. An alternative strategy may therefore be to locally reduce skin mast cell numbers. Here, we explored the possibility of using lysosomotropic agents for this purpose, appreciating the fact that mast cell granules contain bioactive compounds prone to trigger apoptosis if released into the cytosolic compartment. Based on this principle, we show that incubation of human skin punch biopsies with the lysosomotropic agents siramesine or Leu-Leu methyl ester preferably ablated the mast cell population, without causing any gross adverse effects on the skin morphology. Subsequent analysis revealed that mast cells treated with lysosomotropic agents predominantly underwent apoptotic rather than necrotic cell death. In summary, this study raises the possibility of using lysosomotropic agents as a novel approach to targeting deleterious mast cell populations in cutaneous mastocytosis and other skin disorders negatively influenced by mast cells. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multiple bidirectional alterations of phenotype and changes in proliferative potential during the in vitro and in vivo passage of clonal mast cell populations derived from mouse peritoneal mast cells

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

Kanakura, Y.; Thompson, H.; Nakano, T.

1988-09-01

Mouse peritoneal mast cells (PMC) express a connective tissue-type mast cell (CTMC) phenotype, including reactivity with the heparin-binding fluorescent dye berberine sulfate and incorporation of (35S) sulfate predominantly into heparin proteoglycans. When PMC purified to greater than 99% purity were cultured in methylcellulose with IL-3 and IL-4, approximately 25% of the PMC formed colonies, all of which contained both berberine sulfate-positive and berberine sulfate-negative mast cells. When these mast cells were transferred to suspension culture, they generated populations that were 100% berberine sulfate-negative, a characteristic similar to that of mucosal mast cells (MMC), and that synthesized predominantly chondroitin sulfate (35S)more » proteoglycans. When ''MMC-like'' cultured mast cells derived from WBB6F1-+/+ PMC were injected into the peritoneal cavities of mast cell-deficient WBB6F1-W/Wv mice, the adoptively transferred mast cell population became 100% berberine sulfate-positive. In methylcellulose culture, these ''second generation PMC'' formed clonal colonies containing both berberine sulfate-positive and berberine sulfate-negative cells, but exhibited significantly less proliferative ability than did normal +/+ PMC. Thus, clonal mast cell populations initially derived from single PMC exhibited multiple and bidirectional alterations between CTMC-like and MMC-like phenotypes. However, this process was associated with a progressive diminution of the mast cells' proliferative ability.« less

Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression.

PubMed

Wezel, Anouk; Lagraauw, H Maxime; van der Velden, Daniël; de Jager, Saskia C A; Quax, Paul H A; Kuiper, Johan; Bot, Ilze

2015-08-01

Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte recruitment during atherosclerotic plaque progression. Systemic IgE-mediated mast cell activation in apoE(-/-)μMT mice resulted in an increase in atherosclerotic lesion size as compared to control mice, and interestingly, the number of neutrophils was highly increased in these lesions. In addition, peritoneal mast cell activation led to a massive neutrophil influx into the peritoneal cavity in C57Bl6 mice, whereas neutrophil numbers in mast cell deficient Kit(W(-sh)/W(-sh)) mice were not affected. Within the newly recruited neutrophil population, increased levels of CXCR2(+) and CXCR4(+) neutrophils were observed after mast cell activation. Indeed, mast cells were seen to contain and release CXCL1 and CXCL12, the ligands for CXCR2 and CXCR4. Intriguingly, peritoneal mast cell activation in combination with anti-CXCR2 receptor antagonist resulted in decreased neutrophil recruitment, thus establishing a prominent role for the CXCL1/CXCR2 axis in mast cell-mediated neutrophil recruitment. Our data suggest that chemokines, and in particular CXCL1, released from activated mast cells induce neutrophil recruitment to the site of inflammation, thereby aggravating the ongoing inflammatory response and thus affecting plaque progression and destabilization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Xanthelasmoid mastocytosis: a rare form of cutaneous mastocytosis].

PubMed

Ramid, Hind; Hali, Fouzia

2017-01-01

Mastocytosis is a rare disease characterized by the abnormal accumulation of mast cells in the skin and possibly in other organs. It can occur in a variety of forms; xanthelasmoid mastocytosis(XM) is a very rare form classified as papulo-nodular. Clinically, it appears as buff-yellow soft papules or nodules of variable size. Triggerings are those of classic mastocytosis. Darier's sign is often absent. Histology shows dense infiltrate of mast cells in the deep dermis. This clinical form can be singled out because of the persistence of lesions beyond puberty without the additional risk of systemic involvement. We here report the case of a 18-month old female infant, with no previous medical history. Maculopapular, intensely pruritic, ovalaires, brownish lesions with a buff-yellow centre, with elastic consistency and different sizes first occurred at the age of 8 months. The initial interview of parents revealed that the infant had had episode of flush especially caused by warmth. Darrier's sign was negative. Skin biopsy showed dermal infiltrate of mast cells, allowing to retain the diagnosis of xanthelasmoid mastocytosis. Complementary examinations as well as trypsin dosage were normal. Treatment was based on the exclusion of drugs and of factors participating in mast cells degranulation and antihistamines.

Mast cell hyperactivity underpins the development of oxygen-induced retinopathy

PubMed Central

Matsuda, Kenshiro; Okamoto, Noriko; Kondo, Masatoshi; Arkwright, Peter D.; Karasawa, Kaoru; Ishizaka, Saori; Yokota, Shinichi; Matsuda, Akira; Jung, Kyungsook; Oida, Kumiko; Jang, Hyosun; Noda, Eiichiro; Kakinuma, Ryota; Yasui, Koujirou; Kaku, Uiko; Mori, Yasuo; Onai, Nobuyuki; Ohteki, Toshiaki; Tanaka, Akane

2017-01-01

Mast cells are classically thought to play an important role in protection against helminth infections and in the induction of allergic diseases; however, recent studies indicate that these cells also contribute to neovascularization, which is critical for tissue remodeling, chronic inflammation, and carcinogenesis. Here, we demonstrate that mast cells are essential for sprouting angiogenesis in a murine model of oxygen-induced retinopathy (OIR). Although mouse strains lacking mast cells did not exhibit retinal neovascularization following hypoxia, these mice developed OIR following infusion of mast cells or after injection of mast cell tryptase (MCT). Relative hypoxia stimulated mast cell degranulation via transient receptor potential ankyrin 1. Subsequent surges in MCT stimulated retinal endothelial cells to produce monocyte chemotactic protein-1 (MCP1) and angiogenic factors, leading to sprouting angiogenesis. Mast cell stabilizers as well as specific tryptase and MCP1 inhibitors prevented the development of OIR in WT mice. Preterm infants with early retinopathy of prematurity had markedly higher plasma MCT levels than age-matched infants without disease, suggesting mast cells contribute to human disease. Together, these results suggest therapies that suppress mast cell activity should be further explored as a potential option for preventing eye diseases and subsequent blindness induced by neovascularization. PMID:28990934

Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.

PubMed

Coutinho, Agnes E; Brown, Jeremy K; Yang, Fu; Brownstein, David G; Gray, Mohini; Seckl, Jonathan R; Savill, John S; Chapman, Karen E

2013-01-01

Mast cells are key initiators of allergic, anaphylactic and inflammatory reactions, producing mediators that affect vascular permeability, angiogenesis and fibrosis. Glucocorticoid pharmacotherapy reduces mast cell number, maturation and activation but effects at physiological levels are unknown. Within cells, glucocorticoid concentration is modulated by the 11β-hydroxysteroid dehydrogenases (11β-HSDs). Here we show expression and activity of 11β-HSD1, but not 11β-HSD2, in mouse mast cells with 11β-HSD activity only in the keto-reductase direction, regenerating active glucocorticoids (cortisol, corticosterone) from inert substrates (cortisone, 11-dehydrocorticosterone). Mast cells from 11β-HSD1-deficient mice show ultrastructural evidence of increased activation, including piecemeal degranulation and have a reduced threshold for IgG immune complex-induced mast cell degranulation. Consistent with reduced intracellular glucocorticoid action in mast cells, levels of carboxypeptidase A3 mRNA, a glucocorticoid-inducible mast cell-specific transcript, are lower in peritoneal cells from 11β-HSD1-deficient than control mice. These findings suggest that 11β-HSD1-generated glucocorticoids may tonically restrain mast cell degranulation, potentially influencing allergic, anaphylactic and inflammatory responses.

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation[S

PubMed Central

Bot, Martine; de Jager, Saskia C. A.; MacAleese, Luke; Lagraauw, H. Maxime; van Berkel, Theo J. C.; Quax, Paul H. A.; Kuiper, Johan; Heeren, Ron M. A.; Biessen, Erik A. L.; Bot, Ilze

2013-01-01

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability. PMID:23396975

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

PubMed

Bot, Martine; de Jager, Saskia C A; MacAleese, Luke; Lagraauw, H Maxime; van Berkel, Theo J C; Quax, Paul H A; Kuiper, Johan; Heeren, Ron M A; Biessen, Erik A L; Bot, Ilze

2013-05-01

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability.

Synthesis, characterization, and assessment of cytotoxic, antiproliferative, and antiangiogenic effects of a novel procainamide hydrochloride-poly(maleic anhydride-co-styrene) conjugate.

PubMed

Karakus, Gulderen; Akin Polat, Zubeyde; Sahin Yaglıoglu, Ayse; Karahan, Mesut; Yenidunya, Ali Fazil

2013-01-01

Poly(maleic anhydride-co-styrene) (MAST) was synthesized by a free-radical polymerization reaction. A bioactive molecule, procainamide hydrochloride (PH), was then conjugated to MAST. The conjugation product was named as MAST/PH. Structural characterization of MAST and MAST/PH was carried out by Fourier Transform Infrared and Nuclear Magnetic Resonance spectroscopy. Their molecular weights were determined by size-exclusion chromatography. A mechanism was then suggested for the conjugation reaction. The results of the cytotoxicity assay, employing a mouse fibroblast cell line (L929), indicated that MAST/PH had no cytotoxicity at concentrations [Formula: see text] 62 μg mL(-1) (p > 0.05). Antiproliferative activities of MAST/PH and PH were determined by the BrdU cell proliferation ELISA assay, using C6 and HeLa cell lines. In the experiment, two anticancer chemotherapy drugs, cisplatin and 5-fluorouracil, were included as positive control. Antiproliferative activity results demonstrated that MAST/PH yielded the highest suppression profile (approximately 42%) at 20 μg/ml, while free PH exerted the same activity at 100 μg/ml. Interestingly, both MAST/PH and PH suppressed the proliferation of only one of the cell lines, C6 cells. Both cisplatin and 5-fluorouracil yielded approximately 60% antiproliferative activity on C6 cells at 20 and 100 μg/ml concentrations. Antiangiogenic capacity of both MAST and MAST/PH was also investigated by using the chicken chorioallantoic membrane assay. Results obtained indicated that while MAST/PH could be included into the category of good antiangiogenic substances, the activity score of MAST was within the weak category.

Inhibition of neurotensin-stimulated mast cell secretion and carboxypeptidase A activity by the peptide inhibitor of carboxypeptidase A and neurotensin-receptor antagonist SR 48692.

PubMed

Miller, L A; Cochrane, D E; Feldberg, R S; Carraway, R E

1998-06-01

Neurotensin (NT), a peptide found in brain and several peripheral tissues, is a potent stimulus for mast cell secretion and its actions are blocked by the specific NT receptor antagonist, SR 48692. Subsequent to stimulation, NT is rapidly degraded by mast cell carboxypeptidase A (CPA). In the experiments described here, we tested for the involvement of CPA activity in the activation of mast cell secretion by the peptide, NT. Mast cells were isolated from the peritoneal and pleural cavities of rats, purified over metrizamide gradients and incubated at 37 degrees C in Locke solution or Locke containing the appropriate inhibitors. For some experiments, media derived from mast cells stimulated by compound 48/80 were used as a source of mast cell CPA activity. Treatment of mast cells with the highly specific peptide inhibitor of CPA derived from potato (PCI) inhibited histamine release in response to NT and NT8-13 (the biologically active region of NT). This inhibition required some 20 min to develop and was only partially reversed by a 20-min wash period. PCI (10 microM) did not inhibit histamine release in response to NT1-12, bradykinin, compound 48/80, the calcium ionophore, A23187, or anti-IgE serum. PCI also inhibited mast cell CPA activity. SR 48692, a highly selective antagonist of the brain NT receptor and of NT-stimulated mast cell secretion, also inhibited mast cell CPA activity as well as bovine pancreatic CPA activity in a concentration-dependent manner. It is suggested that the mast cell binding site for NT and the active site for CPA may share similar characteristics. The results are discussed in terms of NT mechanism of action on the mast cell.

Mast cells in airway diseases and interstitial lung disease.

PubMed

Cruse, Glenn; Bradding, Peter

2016-05-05

Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease. Published by Elsevier B.V.

Preliminary study on an innovative, simple mast cell-based electrochemical method for detecting foodborne pathogenic bacterial quorum signaling molecules (N-acyl-homoserine-lactones).

PubMed

Jiang, Donglei; Feng, Dongdong; Jiang, Hui; Yuan, Limin; Yongqi, Yin; Xu, Xin; Fang, Weiming

2017-04-15

This paper reports the a novel and simple mast cell-based electrochemical method for detecting of bacterial quorum signaling molecules, N-acylhomoserine lactones (AHLs), which can be utilized to preliminarily evaluate the toxicity of food-borne pathogenic bacteria. Rat basophilic leukemia (RBL-2H3) mast cells encapsulated in alginate/graphene oxide hydrogel were immobilized on a gold electrode, while mast cells as recognition elements were cultured in a 3D cell culture system. Electrochemical impedance spectroscopy (EIS) was utilized to record the cell impedance signal as-influenced by Pseudomonas aeruginosa quorum-sensing molecule, N-3-oxododecanoyl homoserine lactone (3OC 12 -HSL). The results indicated that cellular activities such as cell viability, apoptosis, intracellular calcium, and degranulation were markedly influenced by the AHLs. Importantly, the exposure of 3OC 12 -HSL to mast cells induced a marked decrease in the electrochemical impedance signal in a dose-dependent manner. The detection limit for 3OC 12 -HSL was 0.034μM with a linear range of 0.1-1μM. These results were confirmed via conventional cell assay and transmission electron microscope (TEM) analysis. Altogether, the proposed method appears to be an innovative and effective approach to the quantitative measurement of Gram-negative bacterial quorum signaling molecules; to this effect, it also may serve as a primary evaluation of the cytotoxicity of food-borne pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

ASSESSMENT OF MAST IN EUROPEAN PATIENT-CENTERED TELEMEDICINE PILOTS.

PubMed

Ekeland, Anne Granstrøm; Grøttland, Astrid

2015-01-01

Model for ASsessment of Telemedicine Applications (MAST) is a health technology assessment (HTA) inspired framework for assessing the effectiveness and contribution to quality of telemedicine applications based on rigorous, scientific data. This study reports from a study of how it was used and perceived in twenty-one pilots of the European project RENEWING HEALTH (RH). The objectives of RH were to implement large-scale, real-life test beds for the validation and subsequent evaluation of innovative patient-centered telemedicine services. The study is a contribution to the appraisal of HTA methods. A questionnaire was administered for project leaders of the pilots. It included questions about use and usefulness of MAST for (i) preceding considerations, (ii) evaluation of outcomes within seven domains, and (iii) considerations of transferability. Free text spaces allowed for proposals of improvement. The responses covered all pilots. A quantitative summary of use and a qualitative analysis of usefulness were performed. MAST was used and considered useful for pilot evaluations. Challenges included problems to scientifically determine alternative service options and outcome within the seven domains. Proposals for improvement included process studies and adding domains of technological usability, responsible innovation, health literacy, behavior change, caregiver perspectives and motivational issues of professionals. MAST was used according to its structure. Its usefulness in patient centered pilots can be improved by adding new stakeholder groups. Interdependencies between scientific rigor, resources and timeliness should be addressed. Operational options for improvements include process studies, literature reviews and sequential mini-HTAs for identification of areas for more elaborate investigations.

MAST Propellant and Delivery System Design Methods

NASA Technical Reports Server (NTRS)

Nadeem, Uzair; Mc Cleskey, Carey M.

2015-01-01

A Mars Aerospace Taxi (MAST) concept and propellant storage and delivery case study is undergoing investigation by NASA's Element Design and Architectural Impact (EDAI) design and analysis forum. The MAST lander concept envisions landing with its ascent propellant storage tanks empty and supplying these reusable Mars landers with propellant that is generated and transferred while on the Mars surface. The report provides an overview of the data derived from modeling between different methods of propellant line routing (or "lining") and differentiate the resulting design and operations complexity of fluid and gaseous paths based on a given set of fluid sources and destinations. The EDAI team desires a rough-order-magnitude algorithm for estimating the lining characteristics (i.e., the plumbing mass and complexity) associated different numbers of vehicle propellant sources and destinations. This paper explored the feasibility of preparing a mathematically sound algorithm for this purpose, and offers a method for the EDAI team to implement.

The effect of capsaicin application on mast cells in normal human skin.

PubMed

Bunker, C B; Cerio, R; Bull, H A; Evans, J; Dowd, P M; Foreman, J C

1991-05-01

Peptides released from sensory nerves during an axon reflex are thought to cause mast cell degranulation, histamine (Hi) release and Hi-induced vasodilatation leading to the flare of the triple response. Capsaicin stimulates peptide release from sensory neurones and causes flare in vivo but does not cause Hi release from mast cells in vitro. The effects of capsaicin on mast cell degranulation in human skin in vivo has been studied by histological examination of skin biopsies after topical capsicin (1%) treatment of stratum corneum-denuded forearm in four volunteers. The results show a significant reduction in the visible numbers of mast cells and the appearance of degranulated mast cells ghosts in the skin six hours after capsaicin application. Since capsaicin itself does not release Hi from mast cells, these data suggest that capsaicin-induced release of peptides from neurones could cause mast cell degranulation.

Mast Cells in Allergic Diseases and Mastocytosis

PubMed Central

Marquardt, Diana L.; Wasserman, Stephen I.

1982-01-01

Mast cells with their stores of vasoactive and chemotactic mediators are central to the pathogenesis of allergic diseases. The cross-linking of receptorbound IgE molecules on the surface of mast cells initiates a complex chain of events, including calcium ion influx, phospholipid methylation and turnover and cyclic nucleotide metabolism, ultimately resulting in the release of mediators of immediate hypersensitivity. These mast cell mediators are important in smooth muscle reactivity, in the recruitment of eosinophilic and neutrophilic leukocytes and in the generation of secondary chemical mediators. Histologic evidence of mast cell degranulation, biochemical evidence of mast cell mediators in blood and tissues and clinical evidence of signs and symptoms reproducible by these mediators have strongly supported the crucial role of mast cells in asthma, urticaria, anaphylaxis, rhinitis and mastocytosis. Because of their unique location at host environment interfaces, mast cells may both participate in allergic diseases and promote homeostasis. ImagesFigure 1.Figure 2.Figure 3. PMID:6293204

KSC-2009-1004

NASA Image and Video Library

2009-01-02

CAPE CANAVERAL, Fla. – CAPE CANAVERAL, Fla. -- On Launch Pad 39B at NASA's Kennedy Space Center in Florida, another lightning tower is being constructed as part of the new lightning protection system for the Constellation Program and Ares/Orion launches. Each of the three new lightning towers will be 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Troy Cryder

KSC-2009-1005

NASA Image and Video Library

2009-01-02

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane (at left) completes construction of one of the towers in the new lightning protection system for the Constellation Program and Ares/Orion launches. At right, another tower is being constructed. Each of the three new lightning towers will be 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Troy Cryder

KSC-2009-1301

NASA Image and Video Library

2009-01-22

CAPE CANAVERAL, Fla. – Brilliant beams of sunlight bounce off the new lightning tower under construction on Launch Pad 39B at NASA's Kennedy Space Center in Florida. New sections are being added with the help of a giant crane (at right). Three new lightning towers on the pad will be 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Photo credit: NASA/Kim Shiflett

Antibacterial agent triclosan suppresses RBL-2H3 mast cell function

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

Palmer, Rachel K., E-mail: rachel.palmer@maine.edu; Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469; Hutchinson, Lee M.

2012-01-01

Triclosan is a broad-spectrum antibacterial agent, which has been shown previously to alleviate human allergic skin disease. The purpose of this study was to investigate the hypothesis that the mechanism of this action of triclosan is, in part, due to effects on mast cell function. Mast cells play important roles in allergy, asthma, parasite defense, and carcinogenesis. In response to various stimuli, mast cells degranulate, releasing allergic mediators such as histamine. In order to investigate the potential anti-inflammatory effect of triclosan on mast cells, we monitored the level of degranulation in a mast cell model, rat basophilic leukemia cells, clonemore » 2H3. Having functional homology to human mast cells, as well as a very well defined signaling pathway leading to degranulation, this cell line has been widely used to gain insight into mast-cell driven allergic disorders in humans. Using a fluorescent microplate assay, we determined that triclosan strongly dampened the release of granules from activated rat mast cells starting at 2 μM treatment, with dose-responsive suppression through 30 μM. These concentrations were found to be non-cytotoxic. The inhibition was found to persist when early signaling events (such as IgE receptor aggregation and tyrosine phosphorylation) were bypassed by using calcium ionophore stimulation, indicating that the target for triclosan in this pathway is likely downstream of the calcium signaling event. Triclosan also strongly suppressed F-actin remodeling and cell membrane ruffling, a physiological process that accompanies degranulation. Our finding that triclosan inhibits mast cell function may explain the clinical data mentioned above and supports the use of triclosan or a mechanistically similar compound as a topical treatment for allergic skin disease, such as eczema. -- Highlights: ►The effects of triclosan on mast cell function using a murine mast cell model. ►Triclosan strongly inhibits degranulation of mast cells. ►Triclosan suppresses membrane ruffling of activated mast cells. ►Triclosan's effects persist when early mast cell signaling events are bypassed. ►Supports use of triclosan as a topical treatment for eczema.« less

Distorted secretory granule composition in mast cells with multiple protease deficiency.

PubMed

Grujic, Mirjana; Calounova, Gabriela; Eriksson, Inger; Feyerabend, Thorsten; Rodewald, Hans-Reimer; Tchougounova, Elena; Kjellén, Lena; Pejler, Gunnar

2013-10-01

Mast cells are characterized by an abundance of secretory granules densely packed with inflammatory mediators such as bioactive amines, cytokines, serglycin proteoglycans with negatively charged glycosaminoglycan side chains of either heparin or chondroitin sulfate type, and large amounts of positively charged proteases. Despite the large biological impact of mast cell granules and their contents on various pathologies, the mechanisms that regulate granule composition are incompletely understood. In this study, we hypothesized that granule composition is dependent on a dynamic electrostatic interrelationship between different granule compounds. As a tool to evaluate this possibility, we generated mice in which mast cells are multideficient in a panel of positively charged proteases: the chymase mouse mast cell protease-4, the tryptase mouse mast cell protease-6, and carboxypeptidase A3. Through a posttranslational effect, mast cells from these mice additionally lack mouse mast cell protease-5 protein. Mast cells from mice deficient in individual proteases showed normal morphology. In contrast, mast cells with combined protease deficiency displayed a profound distortion of granule integrity, as seen both by conventional morphological criteria and by transmission electron microscopy. An assessment of granule content revealed that the distorted granule integrity in multiprotease-deficient mast cells was associated with a profound reduction of highly negatively charged heparin, whereas no reduction in chondroitin sulfate storage was observed. Taken together with previous findings showing that the storage of basic proteases conversely is regulated by anionic proteoglycans, these data suggest that secretory granule composition in mast cells is dependent on a dynamic interrelationship between granule compounds of opposite electrical charge.

Mast cell activators as novel immune regulators.

PubMed

Johnson-Weaver, Brandi; Choi, Hae Woong; Abraham, Soman N; Staats, Herman F

2018-05-26

Mast cells are an important cell type of the innate immune system that when activated, play a crucial role in generating protective innate host responses after bacterial and viral infection. Additionally, activated mast cells influence lymph node composition to regulate the induction of adaptive immune responses. The recognition that mast cells play a beneficial role in host responses to microbial infection and induction of adaptive immunity has provided the rationale to evaluate mast cell activators for use as antimicrobials or vaccine adjuvants. This review summarizes the role of mast cell activators in antimicrobial responses while also discussing the use of different classes of mast cell activators as potent vaccine adjuvants that enhance the induction of protective immune responses. Copyright © 2018 Elsevier Ltd. All rights reserved.

Illustrating MastCam Capabilities with a Terrestrial Scene

NASA Image and Video Library

2011-11-28

This set of views illustrates capabilities of the Mast Camera MastCam instrument on NASA Mars Science Laboratory Curiosity rover, using a scene on Earth as an example of what MastCam two cameras can see from different distances.

Mechanism of mast cell adhesion to human tenocytes in vitro.

PubMed

Behzad, Hayedeh; Tsai, Shu-Huei; Nassab, Paulina; Mousavizadeh, Rouhollah; McCormack, Robert G; Scott, Alex

2015-01-01

Mast cells and fibroblasts are two key players involved in many fibrotic and degenerative disorders. In the present study we examined the nature of binding interactions between human mast cells and tendon fibroblasts (tenocytes). In the mast cell-fibroblast co-culture model, mast cells were shown to spontaneously bind to tenocytes, in a process that was partially mediated by α5β1 integrin receptors. The same receptors on mast cells significantly mediated binding of these cells to tissue culture plates in the presence of tenocyte-conditioned media; the tenocyte-derived fibronectin in the media was shown to also play a major role in these binding activities. Upon binding to tenocytes or tissue culture plates, mast cells acquired an elongated phenotype, which was dependent on α5β1 integrin and tenocyte fibronectin. Additionally, tenocyte-derived fibronectin significantly enhanced mRNA expression of the adhesion molecule, THY1, by mast cells. Our data suggests that α5β1 integrin mediates binding of mast cells to human tenocyte and to tenocyte-derived ECM proteins, in particular fibronectin. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Mast Cells in Gastrointestinal Disease

PubMed Central

Ramsay, David B.; Stephen, Sindu; Borum, Marie; Voltaggio, Lysandra

2010-01-01

The function of mast cells in allergic inflammatory reactions is well documented in the literature. Mast cells also play an important role in the regulation of gastrointestinal visceral sensitivity and vascular permeability. Several studies have noted an increased number of mast cells in the mucosa of patients with gastrointestinal diseases such as irritable bowel syndrome, mastocytic enterocolitis, and systemic mastocytosis. The role of mast cells in the symptomatology of these and other diseases has only recently been fully appreciated and could provide avenues for new therapeutic opportunities. This paper examines studies that have evaluated the role of mast cells in various gastrointestinal diseases. PMID:21301631

Suppression of Brain Mast Cells Degranulation Inhibits Microglial Activation and Central Nervous System Inflammation.

PubMed

Dong, Hongquan; Zhang, Xiang; Wang, Yiming; Zhou, Xiqiao; Qian, Yanning; Zhang, Shu

2017-03-01

Brain inflammation has a critical role in the pathophysiology of brain diseases. Microglia, the resident immune cells in the brain, play an important role in brain inflammation, while brain mast cells are the "first responder" in the injury rather than microglia. Functional aspects of mast cell-microglia interactions remain poorly understood. Our results demonstrated that site-directed injection of the "mast cell degranulator" compound 48/80 (C48/80) in the hypothalamus induced mast cell degranulation, microglial activation, and inflammatory factor production, which initiated the acute brain inflammatory response. "Mast cell stabilizer" disodium cromoglycate (cromolyn) inhibited this effect, including decrease of inflammatory cytokines, reduced microglial activation, inhibition of MAPK and AKT pathways, and repression of protein expression of histamine receptor 1 (H 1 R), histamine receptor 4 (H 4 R), protease-activated receptor 2 (PAR2), and toll-like receptor 4 (TLR4) in microglia. We also demonstrated that C48/80 had no effect on microglial activation in mast cell-deficient Kit W-sh/W-sh mice. These results implicate that activated brain mast cells trigger microglial activation and stabilization of mast cell inhibits microglial activation-induced central nervous system (CNS) inflammation. Interactions between mast cells and microglia could constitute a new and unique therapeutic target for CNS immune inflammation-related diseases.

The Mechanism of Anaphylaxis: Specificity of Antigen-Induced Mast Cell Damage in Anaphylaxis in the Guinea Pig

PubMed Central

Humphrey, J. H.; Mota, I.

1959-01-01

Mast cell damage, characterized by loss of granules, occurs when the tissues of sensitized guinea pigs are brought into contact with antigen in vivo or in vitro. Quantitative studies on the mesenteries of passively sensitized guinea pigs show that the mast cell response to antigen is well correlated with the development of anaphylactic shock. After multiple sensitization contact with different antigens caused cumulative, but not complete, disappearance of mast cells. Antigen-antibody interactions, in which antisera were from species which do not sensitize guinea pigs passively for anaphylaxis, did not cause mast cell damage. Reversed passive anaphylaxis and mast cell damage were elicited when the antigen was a suitable γ-globulin, but not an albumin. Antiserum against homologous γ-globulin causes typical anaphylaxis and mast cell degranulation, whereas antiserum against Forssman antigen causes capillary damage without mast cell changes, and antiserum against homologous albumin is ineffective. These findings can be explained by the hypothesis that mast cell damage occurs as a result of antigen-antibody interaction, when one of the reagents is reversibly adsorbed at the mast cell surface, and when they are together capable of activating some process or agent whose further action depends upon the metabolic integrity of the cells. PMID:13640678

Biomarkers for evaluation of mast cell and basophil activation.

PubMed

Kabashima, Kenji; Nakashima, Chisa; Nonomura, Yumi; Otsuka, Atsushi; Cardamone, Chiara; Parente, Roberta; De Feo, Giulia; Triggiani, Massimo

2018-03-01

Mast cells and basophils play a pathogenetic role in allergic, inflammatory, and autoimmune disorders. These cells have different development, anatomical location and life span but share many similarities in mechanisms of activation and type of mediators. Mediators secreted by mast cells and basophils correlate with clinical severity in asthma, chronic urticaria, anaphylaxis, and other diseases. Therefore, effective biomarkers to measure mast cell and basophil activation in vivo could potentially have high diagnostic and prognostic values. An ideal biomarker should be specific for mast cells or basophils, easily and reproducibly detectable in blood or biological fluids and should be metabolically stable. Markers of mast cell and basophil include molecules secreted by stimulated cells and surface molecules expressed upon activation. Some markers, such as histamine and lipid mediators are common to mast cells and basophils whereas others, such as tryptase and other proteases, are relatively specific for mast cells. The best surface markers of activation expressed on mast cells and basophils are CD63 and CD203. While these mediators and surface molecules have been associated to a variety of diseases, none of them fulfills requirements for an optimal biomarker and search for better indicators of mast cell/basophil activation in vivo is ongoing. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Distribution and characterisation of rat choroidal mast cells.

PubMed Central

Steptoe, R J; McMenamin, P G; McMenamin, C

1994-01-01

Despite the implication that choroidal mast cells are involved in the onset of experimental autoimmune uveoretinitis (EAU), a widely used animal model of uveoretinitis, little is known of these cells. In the present study the distribution, total number, regional density, and phenotype of choroidal mast cells were examined in Lewis, Wistar Furth, PVG/c, and brown Norway rats. Choroidal mast cells were predominantly associated with arteries and arterioles of more than 30 microns diameter which lie in the outer (sclerad) choroid. The density of mast cells was greatest in the posterior choroid with density diminishing anteriorly. The choroid of male Lewis rats contained significantly greater number of mast cells than that of females (p < 0.01). Histochemical (Alcian blue/safranin) and immunohistochemical (anti-rat mast cell protease I and II monoclonal antibodies) studies revealed choroidal mast cells were of the connective tissue type. However, granule proteinase content appeared less than that of well characterised connective tissue mast cell populations such as those in mesentery and skin. Lewis rats exhibited the highest density of choroidal mast cells (23.6 (SD 1.2)/mm2), Wistar Furth approximately half that of Lewis (13.5 (0.7)/mm2) while PVG/c and brown Norway rats had very low densities (3.06(0.3); 1.95(0.2/mm2 respectively). These studies provide valuable choroidal mast cell data for rats which may have implications for our understanding of experimental models of intraocular inflammation and clinical uveitis. Images PMID:8148338

Mast cells: potential positive and negative roles in tumor biology.

PubMed

Marichal, Thomas; Tsai, Mindy; Galli, Stephen J

2013-11-01

Mast cells are immune cells that reside in virtually all vascularized tissues. Upon activation by diverse mechanisms, mast cells can secrete a broad array of biologically active products that either are stored in the cytoplasmic granules of the cells (e.g., histamine, heparin, various proteases) or are produced de novo upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). Mast cells are best known for their effector functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. There has been particular interest in the possible roles of mast cells in tumor biology. In vitro studies have shown that mast cells have the potential to influence many aspects of tumor biology, including tumor development, tumor-induced angiogenesis, and tissue remodeling, and the shaping of adaptive immune responses to tumors. Yet, the actual contributions of mast cells to tumor biology in vivo remain controversial. Here, we review some basic features of mast cell biology with a special emphasis on those relevant to their potential roles in tumors. We discuss how using in vivo tumor models in combination with models in which mast cell function can be modulated has implicated mast cells in the regulation of host responses to tumors. Finally, we summarize data from studies of human tumors that suggest either beneficial or detrimental roles for mast cells in tumors. ©2013 AACR.

T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease.

PubMed

Takeuchi, Mai; Sato, Yasuharu; Ohno, Kyotaro; Tanaka, Satoshi; Takata, Katsuyoshi; Gion, Yuka; Orita, Yorihisa; Ito, Toshihiro; Tachibana, Tomoyasu; Yoshino, Tadashi

2014-08-01

IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFβ1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease pathogenesis.

Mast cells and exosomes in hyperoxia-induced neonatal lung disease.

PubMed

Veerappan, A; Thompson, M; Savage, A R; Silverman, M L; Chan, W S; Sung, B; Summers, B; Montelione, K C; Benedict, P; Groh, B; Vicencio, A G; Peinado, H; Worgall, S; Silver, R B

2016-06-01

Chronic lung disease of prematurity (CLD) is a frequent sequela of premature birth and oxygen toxicity is a major associated risk factor. Impaired alveolarization, scarring, and inflammation are hallmarks of CLD. Mast cell hyperplasia is a feature of CLD but the role of mast cells in its pathogenesis is unknown. We hypothesized that mast cell hyperplasia is a consequence of neonatal hyperoxia and contributes to CLD. Additionally, mast cell products may have diagnostic and prognostic value in preterm infants predisposed to CLD. To model CLD, neonatal wild-type and mast cell-deficient mice were placed in an O2 chamber delivering hyperoxic gas mixture [inspired O2 fraction (FiO2 ) of 0.8] (HO) for 2 wk and then returned to room air (RA) for an additional 3 wk. Age-matched controls were kept in RA (FiO2 of 0.21). Lungs from HO mice had increased numbers of mast cells, alveolar simplification and enlargement, and increased lung compliance. Mast cell deficiency proved protective by preserving air space integrity and lung compliance. The mast cell mediators β-hexosaminidase (β-hex), histamine, and elastase increased in the bronchoalveolar lavage fluid of HO wild-type mice. Tracheal aspirate fluids (TAs) from oxygenated and mechanically ventilated preterm infants were analyzed for mast cell products. In TAs from infants with confirmed cases of CLD, β-hex was elevated over time and correlated with FiO2 Mast cell exosomes were also present in the TAs. Collectively, these data show that mast cells play a significant role in hyperoxia-induced lung injury and their products could serve as potential biomarkers in evolving CLD. Copyright © 2016 the American Physiological Society.

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

Lee, Jun Ho; College of Medicine, Korea University, Seoul 136-701; Kim, Tae Hyung

Mast cells, constituents of virtually all organs and tissues, are critical cells in IgE-mediated allergic responses. The aim of this study was to investigate the effect and mechanism of an indoxyl chromogenic compound, 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, on IgE-mediated mast cell activation and allergic responses in mice. CAC-0982 reversibly suppressed antigen-stimulated degranulation in murine mast cells (IC{sub 50}, ~ 3.8 μM) and human mast cells (IC{sub 50}, ~ 3.0 μM). CAC-0982 also inhibited the expression and secretion of IL-4 and TNF-α in mast cells. Furthermore, CAC-0982 suppressed the mast cell-mediated allergic responses in mice in a dose-dependent manner (ED{sub 50} 27.9more » mg/kg). As for the mechanism, CAC-0982 largely suppressed the phosphorylation of Syk and its downstream signaling molecules, including LAT, Akt, Erk1/2, p38, and JNK. Notably, the tyrosine kinase assay of antigen-stimulated mast cells showed that CAC-0982 inhibited Fyn kinase, one of the upstream tyrosine kinases for Syk activation in mast cells. Taken together, these results suggest that CAC-0982 may be used as a new treatment for regulating IgE-mediated allergic diseases through the inhibition of the Fyn/Syk pathway in mast cells. - Highlights: • The anti-allergic effect of 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, was measured. • CAC-0982 reversibly suppressed the activation of mast cells by IgE and antigen. • CAC-0982 inhibited passive cutaneous anaphylaxis in mice. • CAC-0982 suppresses mast cells through inhibition of Fyn activation in mast cells.« less

Regulatory roles of mast cells in immune responses.

PubMed

Morita, Hideaki; Saito, Hirohisa; Matsumoto, Kenji; Nakae, Susumu

2016-09-01

Mast cells are important immune cells for host defense through activation of innate immunity (via toll-like receptors or complement receptors) and acquired immunity (via FcεRI). Conversely, mast cells also act as effector cells that exacerbate development of allergic or autoimmune disorders. Yet, several lines of evidence show that mast cells act as regulatory cells to suppress certain inflammatory diseases. Here, we review the mechanisms by which mast cells suppress diseases.

Widespread immunological functions of mast cells: fact or fiction?

PubMed

Rodewald, Hans-Reimer; Feyerabend, Thorsten B

2012-07-27

Immunological functions of mast cells are currently considered to be much broader than the original role of mast cells in IgE-driven allergic disease. The spectrum of proposed mast cell functions includes areas as diverse as the regulation of innate and adaptive immune responses, protective immunity against viral, microbial, and parasitic pathogens, autoimmunity, tolerance to graft rejection, promotion of or protection from cancer, wound healing, angiogenesis, cardiovascular diseases, diabetes, obesity, and others. The vast majority of in vivo mast cell data have been based on mast cell-deficient Kit mutant mice. However, work in new mouse mutants with unperturbed Kit function, which have a surprisingly normal immune system, has failed to corroborate some key immunological aspects, formerly attributed to mast cells. Here, we consider the implications of these recent developments for the state of the field as well as for future work, aiming at deciphering the physiological functions of mast cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Linking resources with demography to understand resource limitation for bears

USGS Publications Warehouse

Reynolds-Hogland, M. J.; Pacifici, L.B.; Mitchell, M.S.

2007-01-01

1. Identifying the resources that limit growth of animal populations is essential for effective conservation; however, resource limitation is difficult to quantify. Recent advances in geographical information systems (GIS) and resource modelling can be combined with demographic modelling to yield insights into resource limitation. 2. Using long-term data on a population of black bears Ursus americanus, we evaluated competing hypotheses about whether availability of hard mast (acorns and nuts) or soft mast (fleshy fruits) limited bears in the southern Appalachians, USA, during 1981-2002. The effects of clearcutting on habitat quality were also evaluated. Annual survival, recruitment and population growth rate were estimated using capture-recapture data from 101 females. The availability of hard mast, soft mast and clearcuts was estimated with a GIS, as each changed through time as a result of harvest and succession, and then availabilities were incorporated as covariates for each demographic parameter. 3. The model with the additive availability of hard mast and soft mast across the landscape predicted survival and population growth rate. Availability of young clearcuts predicted recruitment, but not population growth or survival. 4. Availability of hard mast stands across the landscape and availability of soft mast across the landscape were more important than hard mast production and availability of soft mast in young clearcuts, respectively. 5. Synthesis and applications. Our results indicate that older stands, which support high levels of hard mast and moderate levels of soft mast, should be maintained to sustain population growth of bears in the southern Appalachians. Simultaneously, the acreage of intermediate aged stands (10-25 years), which support very low levels of both hard mast and soft mast, should be minimized. The approach used in this study has broad application for wildlife management and conservation. State and federal wildlife agencies often possess long-term data on both resource availability and capture-recapture for wild populations. Combined, these two data types can be used to estimate survival, recruitment, population growth, elasticities of vital rates and the effects of resource availability on demographic parameters. Hence data that are traditionally used to understand population trends can be used to evaluate how and why demography changes over time. ?? 2007 The Authors.

Comparison of Mast Cells and Inflammatory Cells within Periapical Lesions and Comparison of Degranulated Mast Cells Between Fibrous and Inflamed Area in Radicular Cysts: An Immunohistochemical Study.

PubMed

Shiromany, Aseem; Sood, Rahul; Akifuddin, Syed; Sidhu, Gagandeep Kaur; Khan, Nadia; Singla, Kapil

2014-12-01

The role of mast cells as the key effector of allergic inflammation, anaphylactic inflammatory reactions and in the pathogenesis of chronic inflammation, is well-known. The present study is adopted to compare mast cells and inflammatory cells within periapical granuloma and cysts and localize the mast cells and quantify their number in the periapical cysts so as to propose a role of mast cells in the pathogenesis of this lesion. Biopsy specimens of 30 periapical lesions were stained with hematoxylin-eosin, and immunohistochemical Mast Cell Tryptase from Bio SB (IHC detection system kit) antibody. The tryptase positive mast cells and mononuclear inflammatory cells were counted in 10 consecutive high power fields (100X) using the binocular microscope from Motic attached to a computer with Motic Advanced Images 3.2 software. Comparative microscopic analysis indicated that periapical cyst shows more percentage of mast cells and less percentage of inflammatory cell than periapical granuloma (comparison of mean and standard deviation of total number of mast cells and inflammatory cells, mast cells 3.15±1.39 in the granuloma group and 4.43±1.91in the cyst group, inflammatory cells, 67.11±1.2 in the granuloma group and 52.66±0.8 in the cyst group). Numerous degranulated mast cells were observed in the fibrous wall than the inflammatory infiltrate of the periapical cysts. The mean and standard deviation of degranulated mast cells between the inflammatory and fibrous zone within the cyst group, being 0.95±1.10 and1.68±1.34 respectively. The values varied significantly between the two zones. The number of inflammatory cells in the cyst group is less than periapical granuloma and total number of mast cells in the cyst group is more as compared to periapical granuloma. The degranulated cells were quantified and they were higher in the fibrous area of the cysts than the inflammatory zone. This study could support the fact that the various mediators released on degranulation play a role in the connective tissue remodeling, chronicity and expansion of the periapical lesion.

Are mast cells important in diabetes?

PubMed

Kempuraj, Duraisamy; Caraffa, Alessandro; Ronconi, Gianpaolo; Lessiani, Gianfranco; Conti, Pio

Diabetes is a metabolic disorder characterized by hyperglycemia and associated with microvascular and macrovascular syndromes mediated by mast cells. Mast cells are activated through cross-linking of their surface high affinity receptors for IgE (FcRI) or other antigens, leading to degranulation and release of stored inflammatory mediators, and cytokines/chemokines without degranulation. Mast cells are implicated in innate and acquired immunity, inflammation and metabolic disorders such as diabetes. Histamine and tryptase genes in mast cells are overexpressed in pancreatic tissue of type 2 diabetes mellitus (T2DM) patients. Histamine is a classic inflammatory mediator generated by activated receptors of mast cells from the histamine-forming enzyme histidine decarboxylase (HDC), which can be activated by two inflammatory chemokines, RANTES and MPC1, when injected intramuscularly or intradermally in mice. This activation is inhibited in genetically mast cell-deficient W/Wv mice, which show higher insulin sensitivity and glucose tolerance. This study contributes to understanding the mechanism by which mast cells profoundly affect diabetes, and their manipulation could represent a new therapeutic strategy. However, further studies are needed to clarify the role of mast cells in inflammation and metabolic disorders such as diabetes.

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

PubMed Central

Zhang, Lei; Song, Jun; Hou, Xiaohua

2016-01-01

Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients. PMID:26755686

Mast Cell Function

PubMed Central

da Silva, Elaine Zayas Marcelino; Jamur, Maria Célia

2014-01-01

Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role. PMID:25062998

Mitigating Uncertainty from Vegetation Spatial Complexity with Highly Portable Lidar

NASA Astrophysics Data System (ADS)

Paynter, I.; Schaaf, C.; Peri, F.; Saenz, E. J.; Genest, D.; Strahler, A. H.; Li, Z.

2015-12-01

To fully utilize the excellent spatial coverage and temporal resolution offered by satellite resources for estimating ecological variables, fine-scale observations are required for comparison, calibration and validation. Lidar instruments have proved effective in estimating the properties of vegetation components of ecosystems, but they are often challenged by occlusion, especially in structurally complex and spatially fragmented ecosystems such as tropical forests. Increasing the range of view angles, both horizontally and vertically, by increasing the number of scans, can mitigate occlusion. However these scans must occur within the window of temporal stability for the ecosystem and vegetation property being measured. The Compact Biomass Lidar (CBL) is a TLS optimized for portability and scanning speed, developed and operated by University of Massachusetts Boston. This 905nm wavelength scanner achieves an angular resolution of 0.25 degrees at a rate of 33 seconds per scan. The ability to acquire many scans within narrow windows of temporal stability for ecological variables has facilitated the more complete investigation of ecosystem structural characteristics, and their expression as a function of view angle. The lightweight CBL has facilitated the use of alternative deployment platforms including towers, trams and masts, allowing analysis of the vertical structure of ecosystems, even in highly enclosed environments such as the sub-canopy of tropical forests where aerial vehicles cannot currently operate. We will present results from view angle analyses of lidar surveys of tropical rainforest in La Selva, Costa Rica where the CBL was deployed at heights up to 10m in Carbono long-term research plots utilizing a portable mast, and on a 25m stationary tower; and temperate forest at Harvard Forest, Massachusetts, USA, where the CBL has been deployed biannually at long-term research plots of hardwood and hemlock, as well as at heights of up to 25m utilizing a stationary tower.

Tumor microvessel density–associated mast cells in canine nodal lymphoma

PubMed Central

Mann, Elizabeth; Whittington, Lisa

2014-01-01

Objective: Mast cells are associated in angiogenesis in various human and animal neoplasms. However, association of mast cells with tumor microvessel density in canine lymphoma was not previously documented. The objective of the study is to determine if mast cells are increased in canine nodal lymphomas and to evaluate their correlation with tumor microvessel density and grading of lymphomas. Methods: Nodal lymphomas from 33 dogs were studied and compared with nonneoplastic lymph nodes from 6 dogs as control. Mast cell count was made on Toluidine blue stained sections. Immunohistochemistry using antibody against Factor VIII was employed to visualize and determine microvessel density. Results: The mast cell count in lymphoma (2.95 ± 2.4) was significantly higher (p < 0.05) than that in the control (0.83 ± 0.3) and was positively correlated with tumor microvessel density (r = 0.44, p = 0.009). Significant difference was not observed in mast cell count and tumor microvessel density among different gradings of lymphomas. Conclusions: Mast cells are associated with tumor microvessel density in canine nodal lymphoma with no significant difference among gradings of lymphomas. Mast cells may play an important role in development of canine nodal lymphomas. Further detailed investigation on the role of mast cells as important part of tumor microenvironment in canine nodal lymphomas is recommended. PMID:26770752

Are Mast Cells MASTers in Cancer?

PubMed Central

Varricchi, Gilda; Galdiero, Maria Rosaria; Loffredo, Stefania; Marone, Giancarlo; Iannone, Raffaella; Marone, Gianni; Granata, Francescopaolo

2017-01-01

Prolonged low-grade inflammation or smoldering inflammation is a hallmark of cancer. Mast cells form a heterogeneous population of immune cells with differences in their ultra-structure, morphology, mediator content, and surface receptors. Mast cells are widely distributed throughout all tissues and are stromal components of the inflammatory microenvironment that modulates tumor initiation and development. Although canonically associated with allergic disorders, mast cells are a major source of pro-tumorigenic (e.g., angiogenic and lymphangiogenic factors) and antitumorigenic molecules (e.g., TNF-α and IL-9), depending on the milieu. In certain neoplasias (e.g., gastric, thyroid and Hodgkin’s lymphoma) mast cells play a pro-tumorigenic role, in others (e.g., breast cancer) a protective role, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of mast cells and their mediators could be cancer specific. The microlocalization (e.g., peritumoral vs intratumoral) of mast cells is another important aspect in the initiation/progression of solid and hematologic tumors. Increasing evidence in certain experimental models indicates that targeting mast cells and/or their mediators represent a potential therapeutic target in cancer. Thus, mast cells deserve focused consideration also as therapeutic targets in different types of tumors. There are many unanswered questions that should be addressed before we understand whether mast cells are an ally, adversary, or innocent bystanders in human cancers. PMID:28446910

Are Mast Cells MASTers in Cancer?

PubMed

Varricchi, Gilda; Galdiero, Maria Rosaria; Loffredo, Stefania; Marone, Giancarlo; Iannone, Raffaella; Marone, Gianni; Granata, Francescopaolo

2017-01-01

Prolonged low-grade inflammation or smoldering inflammation is a hallmark of cancer. Mast cells form a heterogeneous population of immune cells with differences in their ultra-structure, morphology, mediator content, and surface receptors. Mast cells are widely distributed throughout all tissues and are stromal components of the inflammatory microenvironment that modulates tumor initiation and development. Although canonically associated with allergic disorders, mast cells are a major source of pro-tumorigenic (e.g., angiogenic and lymphangiogenic factors) and antitumorigenic molecules (e.g., TNF-α and IL-9), depending on the milieu. In certain neoplasias (e.g., gastric, thyroid and Hodgkin's lymphoma) mast cells play a pro-tumorigenic role, in others (e.g., breast cancer) a protective role, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of mast cells and their mediators could be cancer specific. The microlocalization (e.g., peritumoral vs intratumoral) of mast cells is another important aspect in the initiation/progression of solid and hematologic tumors. Increasing evidence in certain experimental models indicates that targeting mast cells and/or their mediators represent a potential therapeutic target in cancer. Thus, mast cells deserve focused consideration also as therapeutic targets in different types of tumors. There are many unanswered questions that should be addressed before we understand whether mast cells are an ally, adversary, or innocent bystanders in human cancers.

Mast cells in the sheep, hedgehog and rat forebrain

PubMed Central

MICHALOUDI, HELEN C.; PAPADOPOULOS, GEORGIOS C.

1999-01-01

The study was designed to reveal the distribution of various mast cell types in the forebrain of the adult sheep, hedgehog and rat. Based on their histochemical and immunocytochemical characteristics, mast cells were categorised as (1) connective tissue-type mast cells, staining metachromatically purple with the toluidine blue method, or pale red with the Alcian blue/safranin method, (2) mucosal-type or immature mast cells staining blue with the Alcian blue/safranin method and (3) serotonin immunopositive mast cells. All 3 types of brain mast cells in all species studied were located in both white and grey matter, often associated with intraparenchymal blood vessels. Their distribution pattern exhibited interspecies differences, while their number varied considerably not only between species but also between individuals of each species. A distributional left-right asymmetry, with more cells present on the left side, was observed in all species studied but it was most prominent in the sheep brain. In the sheep, mast cells were abundantly distributed in forebrain areas, while in the hedgehog and the rat forebrain, mast cells were less widely distributed and were relatively or substantially fewer in number respectively. A limited number of brain mast cells, in all 3 species, but primarily in the rat, were found to react both immunocytochemically to 5-HT antibody and histochemically with Alcian blue/safranin staining. PMID:10634696

New models for analyzing mast cell functions in vivo

PubMed Central

Reber, Laurent L.; Marichal, Thomas; Galli, Stephen J.

2013-01-01

In addition to their well-accepted role as critical effector cells in anaphylaxis and other acute IgE-mediated allergic reactions, mast cells have been implicated in a wide variety of process that contribute to disease or help to maintain health. While some of these roles were first suggested by analyses of mast cell products or functions in vitro, it is critical to determine whether, and under which circumstances, such potential roles actually can be performed by mast cells in vivo. This review discusses recent advances in the development and analysis of mouse models to investigate the roles of mast cells and mast cell-associated products during biological responses in vivo, and comments on some of the similarities and differences in the results obtained with these newer versus older models of mast cell deficiency. PMID:23127755

Mast cells as effectors in atherosclerosis

PubMed Central

Bot, Ilze; Shi, Guo-Ping; Kovanen, Petri T.

2014-01-01

The mast cell is a potent immune cell known for its functions in host defense responses and diseases such as asthma and allergies. In the past years, accumulating evidence established the contribution of the mast cell to cardiovascular diseases as well, in particular by its effects on atherosclerotic plaque progression and destabilization. Through its release of mediators, such as the mast cell-specific proteases chymase and tryptase, but also of growth factors, histamine and chemokines, activated mast cells can have detrimental effects on its immediate surroundings in the vessel wall. This results in matrix degradation, apoptosis and enhanced recruitment of inflammatory cells, thereby actively contributing to cardiovascular diseases. In this review, we will discuss the current knowledge on mast cell function in cardiovascular diseases and speculate on potential novel therapeutic strategies to prevent acute cardiovascular syndromes via targeting of mast cells. PMID:25104798

Increased mast cell expression of PAR-2 in skin inflammatory diseases and release of IL-8 upon PAR-2 activation.

PubMed

Carvalho, Ricardo Filipe da Silva; Nilsson, Gunnar; Harvima, Ilkka Tapani

2010-02-01

Mast cells are increasingly present in the lesional skin of chronic skin inflammatory diseases including psoriasis and basal cell carcinoma (BCC). It has previously been shown that proteinase-activated receptor (PAR)-2 is expressed by mast cells, and tryptase is a potent activator of this receptor. In this study, skin biopsies from both healthy-looking and lesional skin of patients with psoriasis and superficial spreading BCC were collected and the expression of PAR-2 immunoreactivity in tryptase-positive mast cells was analysed. PAR-2 expression was confirmed in vitro in different mast cell populations. Cord-blood derived mast cells (CBMC) were stimulated with a PAR-2 activating peptide, 2-furoyl-LIGRLO-NH(2). Consequently, IL-8 and histamine production was analysed in the supernatants. We observed a significant increase in the percentage of mast cells expressing PAR-2 in the lesional skin of psoriasis and BCC patients compared with the healthy-looking skin. HMC-1.2, LAD-2 and CBMC mast cells all expressed PAR-2 both intracellularly and on the cell surface. CBMC activation with the PAR-2 activating peptide resulted in an increased secretion of IL-8, but no histamine release was observed. Furthermore, both PAR-2 and IL-8 were co-localized to the same tryptase-positive mast cells in the lesional BCC skin. These results show that mast cells express increased levels of PAR-2 in chronic skin inflammation. Also, mast cells can be activated by a PAR-2 agonist to secrete IL-8, a chemokine which can contribute to the progress of inflammation.

Mast cells promote melanoma colonization of lungs.

PubMed

Öhrvik, Helena; Grujic, Mirjana; Waern, Ida; Gustafson, Ann-Marie; Ernst, Nancy; Roers, Axel; Hartmann, Karin; Pejler, Gunnar

2016-10-18

Mast cells have been implicated in malignant processes, mainly through clinical correlative studies and by experiments performed using animals lacking mast cells due to defective c-kit signaling. However, mast cell-deficient mouse models based on c-kit defects have recently been questioned for their relevance. Here we addressed the effect of mast cells in a tumor setting by using transgenic Mcpt5-Cre+ R-DTA+ mice, in which the deficiency of mast cells is independent of c-kit defects. Melanoma cells (B16.F10) were administered either subcutaneously or intravenously into Mcpt5-Cre+ R-DTA+ mice or Mcpt5-Cre- R-DTA+ littermate controls, followed by the assessment of formed tumors. In the subcutaneous model, mast cells were abundant in the tumor stroma of control mice but were absent in Mcpt5-Cre+ R-DTA+ mice. However, the absence of mast cells did not affect tumor size. In contrast, after intravenous administration of B16.F10 cells, melanoma colonization of the lungs was markedly reduced in Mcpt5-Cre+ R-DTA+ vs. Mcpt5-Cre- R-DTA+ animals. Decreased melanoma colonization of the lungs in Mcpt5-Cre+ R-DTA+ animals was accompanied by increased inflammatory cell recruitment into the bronchoalveolar lavage fluid, suggesting that mast cells suppress inflammation in this setting. Further, qPCR analysis revealed significant alterations in the expression of Twist and E-cadherin in lungs of Mcpt5-Cre+ R-DTA+ vs. control Mcpt5-Cre- R-DTA+ animals, suggesting an impact of mast cells on epithelial-mesenchymal transition. In conclusion, this study reveals that mast cells promote melanoma colonization of the lung.

International Space Station 2A Array Modal Analysis

NASA Technical Reports Server (NTRS)

Laible, Michael; Fitzpatrick, Kristin; Grygier, Michael

2012-01-01

On December 9th 2009, the International Space Station (ISS) 2A solar array mast experienced prolonged longeron shadowing during a Soyuz undocking. Analytical reconstruction of induced thermal and dynamic structural loads showed an exceedance of the mast buckling limit. Possible structural damage to the solar array mast could have occurred during this event. A Low fidelity video survey of the 2A mast showed no obvious damage of the mast longerons or battens. The decision was made to conduct an on-orbit dynamic test of the 2A array on December 18th, 2009. The test included thruster pluming on the array while photogrammetry data was recorded. The test was similar to other Dedicated Thruster Firings (DTFs) that were performed to measure structural frequency and damping of a solar array. Results of the DTF indicated lower frequency mast modes than model predictions, thus leading to speculation of mast damage. A detailed nonlinear analysis was performed on the 2A array model to assess possible solutions to modal differences. The setup of the parametric nonlinear trade study included the use of a detailed array model and the reduced mass and stiffness matrices of the entire ISS being applied to the array interface. The study revealed that the array attachment structure is nonlinear and thus was the source of error in the model prediction of mast modes. In addition, a detailed study was performed to determine mast mode sensitivity to mast longeron damage. This sensitivity study was performed to assess if the ISS program has sufficient instrumentation for mast damage detection.

Mast cell heterogeneity underlies different manifestations of food allergy in mice

PubMed Central

Benedé, Sara

2018-01-01

Food can trigger a diverse array of symptoms in food allergic individuals from isolated local symptoms affecting skin or gut to multi-system severe reactions (systemic anaphylaxis). Although we know that gastrointestinal and systemic manifestations of food allergy are mediated by tissue mast cells (MCs), it is not clear why allergen exposure by the oral route can result in such distinct clinical manifestations. Our aim was to assess the contribution of mast cell subsets to different manifestations of food allergy. We used two common models of IgE-mediated food allergy, one resulting in systemic anaphylaxis and the other resulting in acute gastrointestinal symptoms, to study the immune basis of allergic reactions. We used responders and non-responders in each model system, as well as naïve controls to identify the association of mast cell activation with clinical reactivity rather than sensitization. Systemic anaphylaxis was uniquely associated with activation of connective tissue mast cells (identified by release of mouse mast cell protease (MMCP) -7 into the serum) and release of histamine, while activation of mucosal mast cells (identified by release of MMCP-1 in the serum) did not correlate with symptoms. Gastrointestinal manifestations of food allergy were associated with an increase of MMCP-1-expressing mast cells in the intestine, and evidence of both mucosal and connective tissue mast cell activation. The data presented in this paper demonstrates that mast cell heterogeneity is an important contributor to manifestations of food allergy, and identifies the connective tissue mast cell subset as key in the development of severe systemic anaphylaxis. PMID:29370173

Evaluation of mast cells in periapical cysts, dentigerous cysts, and keratocystic odontogenic tumors.

PubMed

de Noronha Santos Netto, Juliana; Pires, Fábio Ramôa; da Fonseca, Eliene Carvalho; Silva, Licínio Esmeraldo; de Queiroz Chaves Lourenço, Simone

2012-09-01

Several cell types are associated with the development of cystic and tumoral odontogenic lesions. Among inflammatory cells, mast cells can be associated with their pathogenesis. The aim of this study was to analyze mast cells in periapical cysts, dentigerous cysts, and keratocystic odontogenic tumors. Tissue sections were submitted to toluidine blue staining and immunohistochemistry with antibody anti-tryptase (clone G3). Mast cells were quantitated using Image-Pro Plus software to obtain the mean number of mast cells in three regions: epithelial, superficial portion of the fibrous wall and deep portion of the fibrous wall from 20 periapical cysts, 20 dentigerous cysts (six non-inflamed and 14 inflamed) and 20 keratocystic odontogenic tumors (four non-inflamed and 16 inflamed). The mean number of mast cells detected per lesion by immunohistochemistry (4.1) was higher than by histochemistry (1.5) (P<0.0001). Inflamed dentigerous cysts and keratocystic odontogenic tumors showed a higher mean number of mast cells than non-inflamed lesions in all regions. The deep region from all cysts showed the highest mean number of degranulated mast cells, except for non-inflamed keratocystic odontogenic tumors analyzed by immunohistochemistry. Immunohistochemical staining detected higher number of mast cells than histochemistry. The higher number of mast cells observed in inflamed lesions could indicate the participation of these cells in the inflammatory response in odontogenic lesions. The prevalence of degranulated mast cells in the deep region suggests intense activity of these cells, possibly related to growth of cystic lesions. © 2012 John Wiley & Sons A/S.

Airway responsiveness to mannitol in asthma is associated with chymase-positive mast cells and eosinophilic airway inflammation.

PubMed

Sverrild, A; Bergqvist, A; Baines, K J; Porsbjerg, C; Andersson, C K; Thomsen, S F; Hoffmann, H J; Gibson, P; Erjefält, J S; Backer, V

2016-02-01

Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell-associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol. Airway hyperresponsiveness to inhaled mannitol was measured in 23 non-smoking, corticosteroid-free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell-associated genes was measured by real-time PCR. The proportion of submucosal MCTC was higher in asthmatic individuals with AHR to mannitol compared with asthmatic individuals without AHR (median: 40.3% vs. 18.7%, P = 0.03). Increased submucosal MCTC numbers were associated with increased levels of mRNA for thymic stromal lymphopoietin (TSLP) and CPA3 in asthmatics. Reactivity to mannitol correlated significantly with eosinophils in submucosa (r(s): 0.56, P = 0.01). Airway hyperresponsiveness to inhaled mannitol is associated with an altered submucosal mast cell profile in asthmatic individuals. This mast cell profile is associated with increased levels of TSLP and CPA3. The degree of AHR to mannitol is correlated with the degree of eosinophilic inflammation in the airway submucosa. © 2015 John Wiley & Sons Ltd.

HMC-1 human mast cells synthesize neurotensin (NT) precursor, secrete bioactive NT-like peptide(s) and express NT receptor NTS1.

PubMed

Cochrane, David E; Carraway, Robert E; Harrington, Kimberly; Laudano, Melissa; Rawlings, Stephen; Feldberg, Ross S

2011-12-01

To determine if mast cells synthesize the inflammatory peptide, neurotensin (NT), secrete immunoreactive and bioactive NT, and express the NT receptor NTS1. HMC-1 cells, pleural mast cells from Sprague-Dawley rats, LAD2 mast cells, and human cord blood mast cells were used. HMC-1 cells were stimulated with NT, C48/80, mastoparan, or PGE(2). For changes in cutaneous vascular permeability, anesthetized rats were injected intravenously with Evans Blue dye and intradermally with saline, NT, histamine, diphenhydramine, and C48/80. RT-PCR was used to identify RNA transcripts. Histamine was measured by fluorometric assay. In vivo cutaneous vascular permeability assays, radio-immunoassays for NT, Western blotting for the NT precursor protein and NTS1 protein from HMC-1 cells and tissues from rats were used. Immunohistochemistry was used to identify NT precursor-like proteins in HMC-1 mast cells. HMC-1 cells express mRNAs for NT precursor, PC5A processing enzyme and NTS1 receptor. Human cord blood mast cells and LAD2 mast cells express mRNA transcripts for NT precursor and NTS1. Western blotting showed NT precursor and NTS1 receptor in HMC1. Rat tissues with high numbers of mast cells contained NT precursor proteins. NT-like peptides from HMC-1 displayed NT-like bioactivity. HMC-1 mast cells synthesize and secrete immunoreactive and bioactive NT-like peptide(s) and express the NT receptor, suggesting that NT from mast cells might serve autocrine and paracrine roles.

The chemokine receptor CCR1 is identified in mast cell-derived exosomes.

PubMed

Liang, Yuting; Qiao, Longwei; Peng, Xia; Cui, Zelin; Yin, Yue; Liao, Huanjin; Jiang, Min; Li, Li

2018-01-01

Mast cells are important effector cells of the immune system, and mast cell-derived exosomes carrying RNAs play a role in immune regulation. However, the molecular function of mast cell-derived exosomes is currently unknown, and here, we identify differentially expressed genes (DEGs) in mast cells and exosomes. We isolated mast cells derived exosomes through differential centrifugation and screened the DEGs from mast cell-derived exosomes, using the GSE25330 array dataset downloaded from the Gene Expression Omnibus database. Biochemical pathways were analyzed by Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on the online tool DAVID. DEGs-associated protein-protein interaction networks (PPIs) were constructed using the STRING database and Cytoscape software. The genes identified from these bioinformatics analyses were verified by qRT-PCR and Western blot in mast cells and exosomes. We identified 2121 DEGs (843 up and 1278 down-regulated genes) in HMC-1 cell-derived exosomes and HMC-1 cells. The up-regulated DEGs were classified into two significant modules. The chemokine receptor CCR1 was screened as a hub gene and enriched in cytokine-mediated signaling pathway in module one. Seven genes, including CCR1, CD9, KIT, TGFBR1, TLR9, TPSAB1 and TPSB2 were screened and validated through qRT-PCR analysis. We have achieved a comprehensive view of the pivotal genes and pathways in mast cells and exosomes and identified CCR1 as a hub gene in mast cell-derived exosomes. Our results provide novel clues with respect to the biological processes through which mast cell-derived exosomes modulate immune responses.

Mast cell migration to Th2 stimulated airway smooth muscle from asthmatics

PubMed Central

Sutcliffe, A; Kaur, D; Page, S; Woodman, L; Armour, C L; Baraket, M; Bradding, P; Hughes, J M; Brightling, C E

2006-01-01

Background Mast cell microlocalisation within the airway smooth muscle (ASM) bundle is an important determinant of the asthmatic phenotype. We hypothesised that mast cells migrate towards ASM in response to ASM derived chemokines. Methods Primary ASM cultures from subjects with and without asthma were stimulated with interleukin (IL)‐1β, IL‐4, and IL‐13 alone and in combination. Mast cell chemotaxis towards these ASM supernatants was investigated, and the chemotaxins mediating migration by using specific blocking antibodies for stem cell factor (SCF) and the chemokine receptors CCR3, CXCR1, 3 and 4 as well as the Gi inhibitor pertussis toxin and the tyrosine kinase inhibitor genistein were defined. The concentrations of CCL11, CXCL8, CXCL10, TGF‐β, and SCF in the supernatants were measured and the effect of non‐asthmatic ASM supernatants on the mast cell chemotactic activity of asthmatic ASM was examined. Results Human lung mast cells and HMC‐1 cells migrated towards Th2 stimulated ASM from asthmatics but not non‐asthmatics. Mast cell migration was mediated through the combined activation of CCR3 and CXCR1. CCL11 and CXCL8 expression by ASM increased markedly after stimulation, but was similar in those with and without asthma. ASM supernatants from non‐asthmatics inhibited mast cell migration towards the asthmatic ASM supernatant. Conclusion Th2 stimulated ASM from asthmatics is chemotactic for mast cells. Non‐asthmatic ASM releases a mediator or mediators that inhibit mast cell migration towards stimulated asthmatic ASM. Specifically targeting mast cell migration into the ASM bundle may provide a novel treatment for asthma. PMID:16601090

Further studies on rat mast cell degranulation by IgE—anti-IgE and the inhibitory effect of drugs related to cAMP

PubMed Central

Kimura, Y.; Inoue, Yoshie; Honda, H.

1974-01-01

With a modified rat mast cell degranulation (RMCD) technique developed by Korotzer, Haddad and Lopapa (1971), the mechanism of mast cell degranulation by IgE—anti-IgE reaction and the inhibitory effect of cAMP-related compounds upon IgE-mediated mast cell degranulation were studied. Degranulations of 90 per cent or more were decreased to 13–16 per cent when the mast cells were pretreated with human IgE or normal human serum. However, if rat mast cells were pretreated with anti-human IgE rabbit serum or normal rabbit serum, the degranulation per cent in these cells by IgE—anti-IgE reaction was the same as in the nontreated cells. These results suggest the presence of receptors in rat mast cells for human IgE or normal human serum, and the lack of receptors in these cells for anti-human IgE rabbit serum or normal rabbit serum. Treatment of isolated rat mast cells with adenyl cyclase stimulating agents (isoprenaline, adrenaline, prostaglandin E1 and E2) and theophylline or aminophylline, which inhibit the enzymatic degradation of cAMP, also inhibited the morphological degranulation of the mast cells. Cromoglycate or chlorophenes in derivatives, which might have a stabilizing effect of the cell membrane, also inhibited the degranulation of the rat mast cells mediated by IgE—anti-IgE reaction. These results support the attractive hypothesis that cAMP occupies a central modulatory role in the in vitro mast cell degranulation by IgE—anti-IgE reaction. PMID:4368738

Wind Resource Assessment in Complex Terrain with a High-Resolution Numerical Weather Prediction Model

NASA Astrophysics Data System (ADS)

Gruber, Karin; Serafin, Stefano; Grubišić, Vanda; Dorninger, Manfred; Zauner, Rudolf; Fink, Martin

2014-05-01

A crucial step in planning new wind farms is the estimation of the amount of wind energy that can be harvested in possible target sites. Wind resource assessment traditionally entails deployment of masts equipped for wind speed measurements at several heights for a reasonably long period of time. Simplified linear models of atmospheric flow are then used for a spatial extrapolation of point measurements to a wide area. While linear models have been successfully applied in the wind resource assessment in plains and offshore, their reliability in complex terrain is generally poor. This represents a major limitation to wind resource assessment in Austria, where high-altitude locations are being considered for new plant sites, given the higher frequency of sustained winds at such sites. The limitations of linear models stem from two key assumptions in their formulation, the neutral stratification and attached boundary-layer flow, both of which often break down in complex terrain. Consequently, an accurate modeling of near-surface flow over mountains requires the adoption of a NWP model with high horizontal and vertical resolution. This study explores the wind potential of a site in Styria in the North-Eastern Alps. The WRF model is used for simulations with a maximum horizontal resolution of 800 m. Three nested computational domains are defined, with the innermost one encompassing a stretch of the relatively broad Enns Valley, flanked by the main crest of the Alps in the south and the Nördliche Kalkalpen of similar height in the north. In addition to the simulation results, we use data from fourteen 10-m wind measurement sites (of which 7 are located within valleys and 5 near mountain tops) and from 2 masts with anemometers at several heights (at hillside locations) in an area of 1600 km2 around the target site. The potential for wind energy production is assessed using the mean wind speed and turbulence intensity at hub height. The capacity factor is also evaluated, considering the frequency of wind speed between cut-in and cut-out speed and of winds with a low vertical velocity component only. Wind turbines do not turn on at wind speeds below cut-in speed. Wind turbines are taken off from the generator in the case of wind speeds higher than cut-out speed and inclination angles of the wind vector greater than 8o. All of these parameters were computed at each model grid point in the innermost domain in order to map their spatial variability. The results show that in complex terrain the annual mean wind speed at hub height is not sufficient to predict the capacity factor of a turbine; vertical wind speed and the frequency of horizontal wind speed out of the range of cut-in and cut-out speed contribute substantially to a reduction of the energy harvest and locally high turbulence may considerably raise the building costs.

43. TOP PART OF UMBILICAL MAST, NORTH AND WEST SIDES. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

43. TOP PART OF UMBILICAL MAST, NORTH AND WEST SIDES. AIR CONDITIONING DUCTING IS VISIBLE ON INTERIOR OF MAST. RAIL IS VISIBLE LEFT OF THE MAST. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

42. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM MST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

42. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM MST BASE. LAUNCHER IS BEHIND UMBILICAL MAST AND RAIL SYSTEM IS PARALLEL TO MAST ON RIGHT AND LEFT. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Scalability Assessments for the Malicious Activity Simulation Tool (MAST)

DTIC Science & Technology

2012-09-01

the scalability characteristics of MAST. Specifically, we show that an exponential increase in clients using the MAST software does not impact...an exponential increase in clients using the MAST software does not impact network and system resources significantly. Additionally, we...31 1. Hardware .....................................31 2. Software .....................................32 3. Common PC

Cutaneous and systemic mastocytosis in children: a risk factor for anaphylaxis?

PubMed

Matito, A; Carter, M

2015-05-01

Childhood mastocytosis is usually a clonal mast cell disease related to activating mutations in KIT. The symptoms in childhood mastocytosis are typically cutaneous in nature although systemic symptoms including anaphylaxis due to the release of mast cells (MC) mediators can also manifest. The prevalence of anaphylaxis reported in childhood mastocytosis is higher than the rates reported in the pediatric general population, but lower than the prevalence of anaphylaxis described in adult mastocytosis. An extensive cutaneous involvement was reported as a risk factor for anaphylaxis, and patients with diffuse cutaneous mastocytosis have been documented to have more severe anaphylaxis symptoms. Anaphylaxis due to unknown causes or idiopathic anaphylaxis was the primary etiology in pediatric mastocytosis, followed by foods as the most relevant identified trigger; however, hymenoptera stings are not a frequent trigger of anaphylaxis in children with mastocytosis in contrast to the adult patients.

Mast Cell Interactions and Crosstalk in Regulating Allergic Inflammation.

PubMed

Velez, Tania E; Bryce, Paul J; Hulse, Kathryn E

2018-04-17

This review summarizes recent findings on mast cell biology with a focus on IgE-independent roles of mast cells in regulating allergic responses. Recent studies have described novel mast cell-derived molecules, both secreted and membrane-bound, that facilitate cross-talk with a variety of immune effector cells to mediate type 2 inflammatory responses. Mast cells are complex and dynamic cells that are persistent in allergy and are capable of providing signals that lead to the initiation and persistence of allergic mechanisms.

Critical role of mast cells and peroxisome proliferator-activated receptor gamma (PPARγ) in the induction of myeloid-derived suppressor cells by marijuana cannabidiol in vivo

PubMed Central

Hegde, Venkatesh L.; Singh, Udai P.; Nagarkatti, Prakash S.; Nagarkatti, Mitzi

2015-01-01

Cannabidiol (CBD) is a natural non-psychotropic cannabinoid from marijuana (Cannabis sativa) with anti-epileptic and anti-inflammatory properties. Effect of CBD on naïve immune system is not precisely understood. In this study, we observed that administering CBD into naïve mice triggers robust induction of CD11b+Gr-1+ MDSC in the peritoneum, which expressed functional Arg1, and potently suppressed T cell proliferation ex vivo. Further, CBD-MDSC suppressed LPS-induced acute inflammatory response upon adoptive transfer in vivo. CBD-induced suppressor cells were comprised of CD11b+Ly6-G+Ly6-C+ granulocytic and CD11b+Ly6-G−Ly6-C+ monocytic subtypes, with monocytic MDSC exhibiting higher T cell suppressive function. Induction of MDSC by CBD was markedly attenuated in Kit-mutant (KitW/W-v) mast cell-deficient mice. MDSC response was reconstituted upon transfer of WT bone marrow-derived mast cells in KitW/W-v mice suggesting the key role of cKit (CD117) as well as mast cells. Moreover, mast cell activator compound 48/80 induced significant levels of MDSC in vivo. CBD administration in mice induced G-CSF, CXCL1 and M-CSF, but not GM-CSF. G-CSF was found to play a key role in MDSC mobilization inasmuch as neutralizing G-CSF caused a significant decrease in MDSC. Lastly, CBD enhanced the transcriptional activity of PPARγ in luciferase reporter assay, and PPARγ selective antagonist completely inhibited MDSC induction in vivo suggesting its critical role. Together, the results suggest that CBD may induce activation of PPARγ in mast cells leading to secretion of G-CSF and consequent MDSC mobilization. CBD being a major component of Cannabis, our study indicates that marijuana may modulate or dysregulate the immune system by mobilizing MDSC. PMID:25917103

Characterization of Mast Cell Activation Syndrome.

PubMed

Afrin, Lawrence B; Self, Sally; Menk, Jeremiah; Lazarchick, John

2017-03-01

Mast cell activation syndrome (MCAS), a recently recognized nonneoplastic mast cell disease driving chronic multisystem inflammation and allergy, appears prevalent and thus important. We report the first systematic characterization of a large MCAS population. Demographics, comorbidities, symptoms, family histories, physical examination and laboratory findings were reviewed in 298 retrospective and 115 prospective patients with MCAS. Blood samples from prospective subjects were examined by flow cytometry for clonal mast cell disease and tested for cytokines potentially driving the monocytosis frequent in MCAS. Demographically, white females dominated. Median ages at symptom onset and diagnosis were 9 and 49 years, respectively (range: 0-88 and 16-92, respectively) and median time from symptom onset to diagnosis was 30 years (range: 1-85). Median numbers of comorbidities, symptoms, and family medical issues were 11, 20, and 4, respectively (range: 1-66, 2-84, and 0-33, respectively). Gastroesophageal reflux, fatigue and dermatographism were the most common comorbidity, symptom and examination finding. Abnormalities in routine laboratories were common and diverse but typically modest. The most useful diagnostic markers were heparin, prostaglandin D 2 , histamine and chromogranin A. Flow cytometric and cytokine assessments were unhelpful. Our study highlights MCAS׳s morbidity burden and challenging heterogeneity. Recognition is important given good survival and treatment prospects. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Mast cells as effectors in atherosclerosis.

PubMed

Bot, Ilze; Shi, Guo-Ping; Kovanen, Petri T

2015-02-01

The mast cell is a potent immune cell known for its functions in host defense responses and diseases, such as asthma and allergies. In the past years, accumulating evidence established the contribution of the mast cell to cardiovascular diseases as well, in particular, by its effects on atherosclerotic plaque progression and destabilization. Through its release not only of mediators, such as the mast cell-specific proteases chymase and tryptase, but also of growth factors, histamine, and chemokines, activated mast cells can have detrimental effects on its immediate surroundings in the vessel wall. This results in matrix degradation, apoptosis, and enhanced recruitment of inflammatory cells, thereby actively contributing to cardiovascular diseases. In this review, we will discuss the current knowledge on mast cell function in cardiovascular diseases and speculate on potential novel therapeutic strategies to prevent acute cardiovascular syndromes via targeting of mast cells. © 2014 American Heart Association, Inc.

Primary tonsillar mast cell tumour in a dog.

PubMed

Shekell, C C; Thomson, M J; Miller, R I; Mackie, J T

2018-05-01

A 6-year-old speyed female Bull Arab-cross dog was found to have a small tonsillar nodule. Histological examination revealed a well-differentiated mast cell tumour (MCT). At initial staging, no evidence of concurrent cutaneous or visceral MCTs was found on a complete blood count, a single lateral thoracic radiograph, abdominal ultrasound or cytology of the spleen and regional lymph nodes. A diagnosis of primary tonsillar MCT was made. At 40 months postoperatively, the dog is alive with no evidence of gross tumour progression, in contrast to some previous reports of rapid disease progression and metastasis in dogs with primary oral MCTs. To the authors' knowledge, no previous reports of a primary MCT of the tonsil in dogs exist in the veterinary literature. © 2018 Australian Veterinary Association.

30 CFR 57.7004 - Drill mast.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in...

30 CFR 56.7004 - Drill mast.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation unless...

30 CFR 56.7004 - Drill mast.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation unless...

30 CFR 57.7004 - Drill mast.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in...

30 CFR 57.7004 - Drill mast.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in...

30 CFR 57.7004 - Drill mast.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in...

30 CFR 56.7004 - Drill mast.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation unless...

30 CFR 56.7004 - Drill mast.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation unless...

30 CFR 56.7004 - Drill mast.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation unless...

30 CFR 57.7004 - Drill mast.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in...

The Michigan Alcoholism Screening Test (MAST): A Statistical Validation Analysis

ERIC Educational Resources Information Center

Laux, John M.; Newman, Isadore; Brown, Russ

2004-01-01

This study extends the Michigan Alcoholism Screening Test (MAST; M. L. Selzer, 1971) literature base by examining 4 issues related to the validity of the MAST scores. Specifically, the authors examine the validity of the MAST scores in light of the presence of impression management, participant demographic variables, and item endorsement…

Molecular mechanism of mast cell–mediated innate defense against endothelin and snake venom sarafotoxin

PubMed Central

Schneider, Lars A.; Schlenner, Susan M.; Feyerabend, Thorsten B.; Wunderlin, Markus; Rodewald, Hans-Reimer

2007-01-01

Mast cells are protective against snake venom sarafotoxins that belong to the endothelin (ET) peptide family. The molecular mechanism underlying this recently recognized innate defense pathway is unknown, but secretory granule proteases have been invoked. To specifically disrupt a single protease function without affecting expression of other proteases, we have generated a mouse mutant selectively lacking mast cell carboxypeptidase A (Mc-cpa) activity. Using this mutant, we have now identified Mc-cpa as the essential protective mast cell enzyme. Mass spectrometry of peptide substrates after cleavage by normal or mutant mast cells showed that removal of a single amino acid, the C-terminal tryptophan, from ET and sarafotoxin by Mc-cpa is the principle molecular mechanism underlying this very rapid mast cell response. Mast cell proteases can also cleave ET and sarafotoxin internally, but such “nicking” is not protective because intramolecular disulfide bridges maintain peptide function. We conclude that mast cells attack ET and sarafotoxin exactly at the structure required for toxicity, and hence sarafotoxins could not “evade” Mc-cpa's substrate specificity without loss of toxicity. PMID:17923505

Developmental changes of mast cell populations in the cerebral meninges of the rat

PubMed Central

Michaloudi, Helen; Batzios, Christos; Chiotelli, Maria; Papadopoulos, Georgios C

2007-01-01

It is known that both the dura and the pia mater attract and support the differentiation of mast cells. The present study shows that unevenly distributed mast cells in the cerebral meninges of the rat can be found in perivascular sites and vessel ramification points, but can also be unrelated to the meningeal vasculature. It also documents changes in the number, localization and staining preferences of the mast cells in the two meninges of the developing and mature rat brain. Quantitative examination of all types of histochemically differentiated meningeal mast cells reveals no major (although some exist) differences between right and left side subpopulations, but strongly suggests a different origin and fate of the dural and the pial mast cells. The number of dural mast cells, already high from postnatal day 0, although declining from postnatal day 21 onwards, remains conspicuous up to postnatal day 180. In contrast, pial mast cells are comparatively very few in the first day of the postnatal life, and despite a transient significant increase in the following two weeks, they reach almost zero levels from postnatal day 21. PMID:17822416

Meningeal mast cell-T cell crosstalk regulates T cell encephalitogenicity.

PubMed

Russi, Abigail E; Walker-Caulfield, Margaret E; Guo, Yong; Lucchinetti, Claudia F; Brown, Melissa A

2016-09-01

GM-CSF is a cytokine produced by T helper (Th) cells that plays an essential role in orchestrating neuroinflammation in experimental autoimmune encephalomyelitis, a rodent model of multiple sclerosis. Yet where and how Th cells acquire GM-CSF expression is unknown. In this study we identify mast cells in the meninges, tripartite tissues surrounding the brain and spinal cord, as important contributors to antigen-specific Th cell accumulation and GM-CSF expression. In the absence of mast cells, Th cells do not accumulate in the meninges nor produce GM-CSF. Mast cell-T cell co-culture experiments and selective mast cell reconstitution of the meninges of mast cell-deficient mice reveal that resident meningeal mast cells are an early source of caspase-1-dependent IL-1β that licenses Th cells to produce GM-CSF and become encephalitogenic. We also provide evidence of mast cell-T cell co-localization in the meninges and CNS of recently diagnosed acute MS patients indicating similar interactions may occur in human demyelinating disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Developmental changes of mast cell populations in the cerebral meninges of the rat.

PubMed

Michaloudi, Helen; Batzios, Christos; Chiotelli, Maria; Papadopoulos, Georgios C

2007-10-01

It is known that both the dura and the pia mater attract and support the differentiation of mast cells. The present study shows that unevenly distributed mast cells in the cerebral meninges of the rat can be found in perivascular sites and vessel ramification points, but can also be unrelated to the meningeal vasculature. It also documents changes in the number, localization and staining preferences of the mast cells in the two meninges of the developing and mature rat brain. Quantitative examination of all types of histochemically differentiated meningeal mast cells reveals no major (although some exist) differences between right and left side subpopulations, but strongly suggests a different origin and fate of the dural and the pial mast cells. The number of dural mast cells, already high from postnatal day 0, although declining from postnatal day 21 onwards, remains conspicuous up to postnatal day 180. In contrast, pial mast cells are comparatively very few in the first day of the postnatal life, and despite a transient significant increase in the following two weeks, they reach almost zero levels from postnatal day 21.

Expression and function of CD8 alpha/beta chains on rat and human mast cells.

PubMed

Kim, Mi-Sun; Kim, Sung-Hoon; Lee, Hye-Jung; Kim, Hyung-Min

2004-03-01

The expression and functional role of CD8 glycoprotein, a marker of cytotoxic/suppressor T lymphocytes and NK cells, were not studied on freshly isolated connective tissue type rat peritoneal mast cells, a rat mucosal type mast cell line (RBL 2H3), or human mast cell line (HMC-1). We used the reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, immunohistochemistry and enzyme-linked immunosorbent assay. RT-PCR and Western blot analysis identified the presence of CD8 alpha/beta chains on the mast cells, and immunohistochemistry confirmed CD8alpha expression on rat or human mast cells. Functional studies demonstrated that stimulation of CD8 alpha/beta chains on rat mast cells induced the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), which are regarded as important mediators during infection. However, co-stimulation with stem cell factor had no effect on CD8-induced mediator secretion. Our findings demonstrate novel biological roles of CD8 molecules in mast cells.

Contribution of engineered nanomaterials physicochemical properties to mast cell degranulation

NASA Astrophysics Data System (ADS)

Johnson, Monica M.; Mendoza, Ryan; Raghavendra, Achyut J.; Podila, Ramakrishna; Brown, Jared M.

2017-03-01

The rapid development of engineered nanomaterials (ENMs) has grown dramatically in the last decade, with increased use in consumer products, industrial materials, and nanomedicines. However, due to increased manufacturing, there is concern that human and environmental exposures may lead to adverse immune outcomes. Mast cells, central to the innate immune response, are one of the earliest sensors of environmental insult and have been shown to play a role in ENM-mediated immune responses. Our laboratory previously determined that mast cells are activated via a non-FcɛRI mediated response following silver nanoparticle (Ag NP) exposure, which was dependent upon key physicochemical properties. Using bone marrow-derived mast cells (BMMCs), we tested the hypothesis that ENM physicochemical properties influence mast cell degranulation. Exposure to 13 physicochemically distinct ENMs caused a range of mast degranulation responses, with smaller sized Ag NPs (5 nm and 20 nm) causing the most dramatic response. Mast cell responses were dependent on ENMs physicochemical properties such as size, apparent surface area, and zeta potential. Surprisingly, minimal ENM cellular association by mast cells was not correlated with mast cell degranulation. This study suggests that a subset of ENMs may elicit an allergic response and contribute to the exacerbation of allergic diseases.

Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem cell factor

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

Tsai, M.; Takeishi, Takashi; Geissler, E.N.

1991-07-15

The authors investigated the effects of a newly recognized multifunctional growth factor, the c-kit ligand stem cell factor (SCF), on mouse mast cell proliferation and phenotype. Recombinant rat SCF{sup 164} (rrSCF{sup 164}) induced the development of large numbers of dermal mast cells in normal mice in vivo. Many of these mast cells had features of connective tissue-type mast cells (CTMC), in that they were reactive both with the heparin-binding fluorescent dye berberine sulfate and with safranin. In vitro, rrSCF{sup 164} induced the proliferation of cloned interleukin 3 (IL-3)-dependent mouse mast cells and primary populations of IL-3-dependent, bone marrow-derived cultured mastmore » cells (BMCMC), which represent immature mast cells, and purified peritoneal mast cells, which represent a type of mature CTMC> BMCMC maintained in rrSCF{sup 164} not only proliferated but also matured. These findings identify SCF as a single cytokine that can induce immature, IL-3-dependent mast cells to mature and to acquire multiple characteristics of CTMC. These findings also directly demonstrate that SCF can regulate the development of a cellular lineage expressing c-kit through effects on both proliferation and maturation.« less

Mast cells contribute to scar formation during fetal wound healing.

PubMed

Wulff, Brian C; Parent, Allison E; Meleski, Melissa A; DiPietro, Luisa A; Schrementi, Megan E; Wilgus, Traci A

2012-02-01

Scar formation is a potentially detrimental process of tissue restoration in adults, affecting organ form and function. During fetal development, cutaneous wounds heal without inflammation or scarring at early stages of development; however, they begin to heal with significant inflammation and scarring as the skin becomes more mature. One possible cell type that could regulate the change from scarless to fibrotic healing is the mast cell. We show here that dermal mast cells in scarless wounds generated at embryonic day 15 (E15) are fewer in number, less mature, and do not degranulate in response to wounding as effectively as mast cells of fibrotic wounds made at embryonic day 18 (E18). Differences were also observed between cultured mast cells from E15 and E18 skin, with regard to degranulation and preformed cytokine levels. Injection of mast cell lysates into E15 wounds disrupted scarless healing, suggesting that mast cells interfere with scarless repair. Finally, wounds produced at E18, which normally heal with a scar, healed with significantly smaller scars in mast cell-deficient Kit(W/W-v) mice compared with Kit(+/+) littermates. Together, these data suggest that mast cells enhance scar formation, and that these cells may mediate the transition from scarless to fibrotic healing during fetal development.

An essential role for platelet-activating factor in activating mast cell migration following ultraviolet irradiation

PubMed Central

Chacón-Salinas, Rommel; Chen, Limo; Chávez-Blanco, Alma D.; Limón-Flores, Alberto Y.; Ma, Ying; Ullrich, Stephen E.

2014-01-01

The UVB (290–320 nm) radiation in sunlight is responsible for inducing skin cancer. Exposure to UV radiation is also immunosuppressive, and the systemic immune suppression induced by UV is a well-recognized risk factor for cancer induction. As UVB radiation is absorbed within the upper layers of the skin, indirect mechanisms must play a role in activating systemic immune suppression. One prominent example is mast cell migration, which from the skin to the draining LN is an essential step in the cascade of events leading to immune suppression. What triggers mast cell migration is not entirely clear. Here, we tested the hypothesis that PAF, a lipid mediator of inflammation produced by the skin in response to UV exposure, is involved. Mast cell-deficient mice (KitW-sh/W-sh) are resistant to the suppressive effect of UV radiation, and reconstituting mast cell-deficient mice with normal bone marrow-derived mast cells restores susceptibility to immunosuppression. However, when mast cells from PAFR−/− mice were used, the reconstituted mice were not susceptible to the suppressive effects of UV. Furthermore, PAFR−/− mice showed impaired UV-induced mast cell migration when compared with WT mice. Finally, injecting PAF into WT mice mimicked the effect of UV irradiation and induced mast cell migration but not in PAFR−/− mice. Our findings indicate that PAFR binding induces mast cells to migrate from the skin to the LNs, where they mediate immune suppression. PMID:24009177

Advantages of masting in European beech: timing of granivore satiation and benefits of seed caching support the predator dispersal hypothesis.

PubMed

Zwolak, Rafał; Bogdziewicz, Michał; Wróbel, Aleksandra; Crone, Elizabeth E

2016-03-01

The predator satiation and predator dispersal hypotheses provide alternative explanations for masting. Both assume satiation of seed-eating vertebrates. They differ in whether satiation occurs before or after seed removal and caching by granivores (predator satiation and predator dispersal, respectively). This difference is largely unrecognized, but it is demographically important because cached seeds are dispersed and often have a microsite advantage over nondispersed seeds. We conducted rodent exclosure experiments in two mast and two nonmast years to test predictions of the predator dispersal hypothesis in our study system of yellow-necked mice (Apodemus flavicollis) and European beech (Fagus sylvatica). Specifically, we tested whether the fraction of seeds removed from the forest floor is similar during mast and nonmast years (i.e., lack of satiation before seed caching), whether masting decreases the removal of cached seeds (i.e., satiation after seed storage), and whether seed caching increases the probability of seedling emergence. We found that masting did not result in satiation at the seed removal stage. However, masting decreased the removal of cached seeds, and seed caching dramatically increased the probability of seedling emergence relative to noncached seeds. European beech thus benefits from masting through the satiation of scatterhoarders that occurs only after seeds are removed and cached. Although these findings do not exclude other evolutionary advantages of beech masting, they indicate that fitness benefits of masting extend beyond the most commonly considered advantages of predator satiation and increased pollination efficiency.

Influence of MRI contrast media on histamine release from mast cells.

PubMed

Kun, Tomasz; Jakubowski, Lucjusz

2012-07-01

Mast cells, owing to diversity of secreted mediators, play a crucial role in the regulation of inflammatory response. Together with basophils, mast cells constitute a central pathogenetic element of anaphylactic (IgE-dependent) and anaphylactoid (IgE-independent) reactions. In severe cases, generalized degranulation of mast cells may cause symptoms of anaphylactic shock. The influence of the classical, iodine-based contrast media on mastocyte degranulation has been fully described. Our objective was to determine the influence of the gadolinium-based MRI contrast media on histamine release from mast cells and to compare the activity of ionic and non-ionic preparations of contrast media. To determine the intensity of mast cell degranulation, we used an experimental model based on mastocytes isolated from rat peritoneal fluid. Purified suspensions of mast cells were incubated with various concentrations of Gd-DTPA and Gd-DTPA-BMA, and solutions of PEG 600 which served as a non-toxic osmotic stimulus. The intensity of mast cell activation was presented as mean percentage of histamine released from cells after incubation. The obtained results demonstrate that both ionic and non-ionic preparations of the MRI contrast media are able to induce mast cell degranulation in vitro. It was also proved that the non-ionic MRI contrast media stimulate mast cells markedly more weakly than ionic contrast media at identical concentration. The aforementioned results may suggest a more profitable safety profile of the non-ionic contrast preparations. We may also conclude that triggering of mast cell degranulation after incubation with the solutions of MRI contrast media results from non-specific osmotic stimulation and direct toxicity of free ionic residues.

Beyond The Prime Directive: The MAST Discovery Portal and High Level Science Products

NASA Astrophysics Data System (ADS)

Fleming, Scott W.; Abney, Faith; Donaldson, Tom; Dower, Theresa; Fraquelli, Dorothy A.; Koekemoer, Anton M.; Levay, Karen; Matuskey, Jacob; McLean, Brian; Quick, Lee; Rogers, Anthony; Shiao, Bernie; Thompson, Randy; Tseng, Shui-Ay; Wallace, Geoff; White, Richard L.

2015-01-01

The Mikulski Archive for Space Telescopes (MAST) is a NASA-funded archive for a wide range of astronomical missions, primarily supporting space-based UV and optical telescopes. What is less well-known is that MAST provides much more than just a final resting place for primary data products and documentation from these missions. The MAST Discovery Portal is our new search interface that integrates all the missions that MAST supports into a single interface, allowing users to discover (and retrieve) data from other missions that overlap with your targets of interest. In addition to searching MAST, the Portal allows users to search the Virtual Observatory, granting access to data from thousands of collections registered with the VO, including large missions spanning the electromagnetic spectrum (e.g., Chandra, SDSS, Spitzer, 2MASS, WISE). The Portal features table import/export, coordinate-based cross-matching, dynamic chart plotting, and the AstroView sky viewer with footprint overlays. We highlight some of these capabilities with science-driven examples. MAST also accepts High Level Science Products (HLSPs) from the community. These HLSPs are user-generated data products that can be related to a MAST-supported mission. MAST provides a permanent archive for these data with linked references, and integrates it within MAST infrastructure and services. We highlight some of the most recent HLSPs MAST has released, including the HST Frontier Fields, GALEX All-Sky Diffuse Radiation Mapping, a survey of the intergalactic medium with HST-COS, and one of the most complete line lists ever derived for a white dwarf using FUSE AND HST-STIS. These HLSPs generate substantial interest from the community, and are an excellent way to increase visibility and ensure the longevity of your data.

The chemokine receptor CCR1 is identified in mast cell-derived exosomes

PubMed Central

Liang, Yuting; Qiao, Longwei; Peng, Xia; Cui, Zelin; Yin, Yue; Liao, Huanjin; Jiang, Min; Li, Li

2018-01-01

Mast cells are important effector cells of the immune system, and mast cell-derived exosomes carrying RNAs play a role in immune regulation. However, the molecular function of mast cell-derived exosomes is currently unknown, and here, we identify differentially expressed genes (DEGs) in mast cells and exosomes. We isolated mast cells derived exosomes through differential centrifugation and screened the DEGs from mast cell-derived exosomes, using the GSE25330 array dataset downloaded from the Gene Expression Omnibus database. Biochemical pathways were analyzed by Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on the online tool DAVID. DEGs-associated protein-protein interaction networks (PPIs) were constructed using the STRING database and Cytoscape software. The genes identified from these bioinformatics analyses were verified by qRT-PCR and Western blot in mast cells and exosomes. We identified 2121 DEGs (843 up and 1278 down-regulated genes) in HMC-1 cell-derived exosomes and HMC-1 cells. The up-regulated DEGs were classified into two significant modules. The chemokine receptor CCR1 was screened as a hub gene and enriched in cytokine-mediated signaling pathway in module one. Seven genes, including CCR1, CD9, KIT, TGFBR1, TLR9, TPSAB1 and TPSB2 were screened and validated through qRT-PCR analysis. We have achieved a comprehensive view of the pivotal genes and pathways in mast cells and exosomes and identified CCR1 as a hub gene in mast cell-derived exosomes. Our results provide novel clues with respect to the biological processes through which mast cell-derived exosomes modulate immune responses. PMID:29511430

Equine Airway Mast Cells are Sensitive to Cell Death Induced by Lysosomotropic Agents.

PubMed

Wernersson, S; Riihimäki, M; Pejler, G; Waern, I

2017-01-01

Mast cells are known for their detrimental effects in various inflammatory conditions. Regimens that induce selective mast cell apoptosis may therefore be of therapeutic significance. Earlier studies have demonstrated that murine- and human-cultured mast cells are highly sensitive to apoptosis induced by the lysosomotropic agent LeuLeuOMe (LLME). However, the efficacy of lysosomotropic agents for inducing apoptosis of in vivo-derived airway mast cells and the impact on mast cells in other species have not been assessed. Here we addressed whether lysosomotropic agents can induce cell death of equine in vivo-derived mast cells. Bronchoalveolar lavage (BAL) fluids from horses were incubated with LLME at 15-100 μm for up to 48 h. The overall cell viability was unaffected by 15 μm LLME up to 48 h, whereas a relatively modest drop in total cell counts (~30%) was seen at the highest LLME dose used. In contrast to the relatively low effect on total cell counts, LLME efficiently and dose dependently reduced the number of mast cells in BAL fluids, with an almost complete depletion (96%) of mast cells after 24 h of incubation with 100 μm LLME. A significant but less dramatic reduction (up to ~45%) of lymphocytes was also seen, whereas macrophages and neutrophils were essentially resistant. The appearance of apoptotic bodies suggested a mechanism involving apoptosis rather than necrosis. These findings suggest that equine airway mast cells are highly sensitive to lysosomotropic agents. Possibly, lysosomotropic agents could be of therapeutic value to treat disorders involving harmful accumulation of mast cells in the airways. © 2016 The Foundation for the Scandinavian Journal of Immunology.

Urinary and faecal N-methylhistamine concentrations do not serve as markers for mast cell activation or clinical disease activity in dogs with chronic enteropathies.

PubMed

Anfinsen, Kristin P; Berghoff, Nora; Priestnall, Simon L; Suchodolski, Jan S; Steiner, Jörg M; Allenspach, Karin

2014-12-21

This study sought to correlate faecal and urinary N-methylhistamine (NMH) concentrations with resting versus degranulated duodenal mast cell numbers in dogs with chronic enteropathies (CE), and investigate correlations between intestinal mast cell activation and clinical severity of disease as assessed by canine chronic enteropathy clinical activity index (CCECAI), and between urinary and faecal NMH concentrations, mast cell numbers, and histopathological scores. Twenty-eight dogs with CE were included. Duodenal biopsies were stained with haematoxylin and eosin (H&E), toluidine blue, and by immunohistochemical labelling for tryptase. Duodenal biopsies were assigned a histopathological severity score, and duodenal mast cell numbers were counted in five high-power fields after metachromatic and immunohistochemical staining. Faecal and urinary NMH concentrations were measured by gas chromatography-mass spectrometry. There was no correlation between the CCECAI and faecal or urinary NMH concentrations, mast cell numbers, or histopathological score - or between faecal or urinary NMH concentration and mast cell numbers. Post hoc analysis revealed a statistically significant difference in toluidine blue positive mast cells between two treatment groups (exclusion diet with/without metronidazole versus immunosuppression (IS)), with higher numbers among dogs not requiring IS. Faecal and urinary NMH concentrations and duodenal mast cell numbers were not useful indicators of severity of disease as assessed by the CCECAI or histological evaluation. The number of duodenal mast cells was higher in dogs that did not need IS, i.e. in dogs responding to an exclusion diet (with/without metronidazole), than in dogs requiring IS. Further studies comparing the role of mast cells in dogs with different forms of CE are needed.

Aging-associated shifts in functional status of mast cells located by adult and aged mesenteric lymphatic vessels

PubMed Central

Chatterjee, Victor

2012-01-01

We had previously proposed the presence of permanent stimulatory influences in the tissue microenvironment surrounding the aged mesenteric lymphatic vessels (MLV), which influence aged lymphatic function. In this study, we performed immunohistochemical labeling of proteins known to be present in mast cells (mast cell tryptase, c-kit, prostaglandin D2 synthase, histidine decarboxylase, histamine, transmembrane protein 16A, and TNF-α) with double verification of mast cells in the same segment of rat mesentery containing MLV by labeling with Alexa Fluor 488-conjugated avidin followed by toluidine blue staining. Additionally, we evaluated the aging-associated changes in the number of mast cells located by MLV and in their functional status by inducing mast cell activation by various activators (substance P; anti-rat DNP Immunoglobulin E; peptidoglycan from Staphyloccus aureus and compound 48/80) in the presence of ruthenium red followed by subsequent staining by toluidine blue. We found that there was a 27% aging-associated increase in the total number of mast cells, with an ∼400% increase in the number of activated mast cells in aged mesenteric tissue in resting conditions with diminished ability of mast cells to be newly activated in the presence of inflammatory or chemical stimuli. We conclude that higher degree of preactivation of mast cells in aged mesenteric tissue is important for development of aging-associated impairment of function of mesenteric lymphatic vessels. The limited number of intact aged mast cells located close to the mesenteric lymphatic compartments to react to the presence of acute stimuli may be considered contributory to the aging-associated deteriorations in immune response. PMID:22796537

4-Chlorotetrazolo[1,5-a]quinoxaline inhibits activation of Syk kinase to suppress mast cells in vitro and mast cell-mediated passive cutaneous anaphylaxis in mice

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

Park, Kui Lea; Ko, Na Young; Lee, Jun Ho

2011-12-15

4-Chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. We aimed to study the effects of 4-chlorotetrazolo[1,5-a]quinoxaline on activation of mast cells in vitro and in mice. 4-Chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited degranulation of mast cells in a dose-dependent manner, and also suppressed the expression and secretion of TNF-{alpha} and IL-4 in mast cells. Mechanistically, 4-chlorotetrazolo[1,5-a]quinoxaline inhibited activating phosphorylation of Syk and LAT, which are crucial for early Fc{epsilon}RI-mediated signaling events, as well as Akt and MAP kinases, which play essential roles in the production of various pro-inflammatory cytokines in mast cells. Notably, although 4-chlorotetrazolo[1,5-a]quinoxaline inhibited the activation of Fyn and Syk, minimal inhibition was observedmore » in mast cells in the case of Lyn. Furthermore, consistent with its in vitro activity, 4-chlorotetrazolo[1,5-a]quinoxaline significantly suppressed mast cell-mediated passive cutaneous anaphylaxis in mice. In summary, the results from this study demonstrate that 4-chlorotetrazolo[1,5-a]quinoxaline shows an inhibitory effect on mast cells in vitro and in vivo, and that this is mediated by inhibiting the activation of Syk in mast cells. Therefore, 4-chlorotetrazolo[1,5-a]quinoxaline could be useful in the treatment of mast cell-mediated allergic diseases. -- Highlights: Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. Black-Right-Pointing-Pointer The effect of 4-chlorotetrazolo[1,5-a]quinoxaline on mast cells was investigated. Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited Syk activation. Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline could be useful for IgE-mediated allergy.« less

Mast cells play no role in the pathogenesis of postoperative ileus induced by intestinal manipulation.

PubMed

Gomez-Pinilla, Pedro J; Farro, Giovanna; Di Giovangiulio, Martina; Stakenborg, Nathalie; Némethova, Andrea; de Vries, Annick; Liston, Adrian; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Rodewald, Hans-Reimwer; Boeckxstaens, Guy E; Matteoli, Gianluca

2014-01-01

Intestinal manipulation (IM) during abdominal surgery results in intestinal inflammation leading to hypomotility or ileus. Mast cell activation is thought to play a crucial role in the pathophysiology of postoperative ileus (POI). However, this conclusion was mainly drawn using mast cell-deficient mouse models with abnormal Kit signaling. These mice also lack interstitial cells of Cajal (ICC) resulting in aberrant gastrointestinal motility even prior to surgery, compromising their use as model to study POI. To avoid these experimental weaknesses we took advantage of a newly developed knock-in mouse model, Cpa3(Cre/+) , devoid of mast cells but with intact Kit signaling. The role of mast cells in the development of POI and intestinal inflammation was evaluated assessing gastrointestinal transit and muscularis externa inflammation after IM in two strains of mice lacking mast cells, i.e. Kit(W-sh/W-sh) and Cpa3(Cre/+) mice, and by use of the mast cell stabilizer cromolyn. Kit(W-sh/W-sh) mice lack ICC networks and already revealed significantly delayed gastrointestinal transit even before surgery. IM did not further delay intestinal transit, but induced infiltration of myeloperoxidase positive cells, expression of inflammatory cytokines and recruitment of monocytes and neutrophils into the muscularis externa. On the contrary, Cpa3(Cre/+) mice have a normal network of ICC and normal gastrointestinal. Surprisingly, IM in Cpa3(Cre/+) mice caused delay in gut motility and intestinal inflammation as in wild type littermates mice (Cpa3(+/+) ). Furthermore, treatment with the mast cell inhibitor cromolyn resulted in an inhibition of mast cells without preventing POI. Here, we confirm that IM induced mast cell degranulation. However, our data demonstrate that mast cells are not required for the pathogenesis of POI in mice. Although there might be species differences between mouse and human, our results argue against mast cell inhibitors as a therapeutic approach to shorten POI.

Mast Cells Play No Role in the Pathogenesis of Postoperative Ileus Induced by Intestinal Manipulation

PubMed Central

Gomez-Pinilla, Pedro J.; Farro, Giovanna; Di Giovangiulio, Martina; Stakenborg, Nathalie; Némethova, Andrea; de Vries, Annick; Liston, Adrian; Feyerabend, Thorsten B.; Rodewald, Hans-Reimwer; Boeckxstaens, Guy E.; Matteoli, Gianluca

2014-01-01

Introduction Intestinal manipulation (IM) during abdominal surgery results in intestinal inflammation leading to hypomotility or ileus. Mast cell activation is thought to play a crucial role in the pathophysiology of postoperative ileus (POI). However, this conclusion was mainly drawn using mast cell-deficient mouse models with abnormal Kit signaling. These mice also lack interstitial cells of Cajal (ICC) resulting in aberrant gastrointestinal motility even prior to surgery, compromising their use as model to study POI. To avoid these experimental weaknesses we took advantage of a newly developed knock-in mouse model, Cpa3Cre/+, devoid of mast cells but with intact Kit signaling. Design The role of mast cells in the development of POI and intestinal inflammation was evaluated assessing gastrointestinal transit and muscularis externa inflammation after IM in two strains of mice lacking mast cells, i.e. KitW-sh/W-sh and Cpa3Cre/+ mice, and by use of the mast cell stabilizer cromolyn. Results KitW-sh/W-sh mice lack ICC networks and already revealed significantly delayed gastrointestinal transit even before surgery. IM did not further delay intestinal transit, but induced infiltration of myeloperoxidase positive cells, expression of inflammatory cytokines and recruitment of monocytes and neutrophils into the muscularis externa. On the contrary, Cpa3Cre/+ mice have a normal network of ICC and normal gastrointestinal. Surprisingly, IM in Cpa3Cre/+ mice caused delay in gut motility and intestinal inflammation as in wild type littermates mice (Cpa3+/+). Furthermore, treatment with the mast cell inhibitor cromolyn resulted in an inhibition of mast cells without preventing POI. Conclusions Here, we confirm that IM induced mast cell degranulation. However, our data demonstrate that mast cells are not required for the pathogenesis of POI in mice. Although there might be species differences between mouse and human, our results argue against mast cell inhibitors as a therapeutic approach to shorten POI. PMID:24416383

Calcium Imaging of Nerve-Mast Cell Signaling in the Human Intestine

PubMed Central

Buhner, Sabine; Barki, Natasja; Greiter, Wolfgang; Giesbertz, Pieter; Demir, Ihsan E.; Ceyhan, Güralp O.; Zeller, Florian; Daniel, Hannelore; Schemann, Michael

2017-01-01

Introduction: It is suggested that an altered microenvironment in the gut wall alters communication along a mast cell nerve axis. We aimed to record for the first time signaling between mast cells and neurons in intact human submucous preparations. Methods: We used the Ca2+ sensitive dye Fluo-4 AM to simultaneously image changes in intracellular calcium [Ca+2]i (%ΔF/F) in neurons and mast cells. Data are presented as median with interquartile ranges (25/75%). Results: We recorded nerve responses in 29 samples upon selective activation of 223 mast cells by IgE receptor cross linking with the antibody mAb22E7. Mast cells responded to mAb22E7 with a median [Ca+2]i increase of 20% (11/39) peaking 90 s (64/144) after the application. Only very few neurons responded and the median percentage of responding neuronal area was 0% (0/5.9). Mast cell activation remained in the presence of the fast sodium channel blocker tetrodotoxin. Specific neuronal activation by transmural electrical field stimulation (EFS) in 34 samples evoked instantaneously [Ca+2]i signals in submucous neurons. This was followed by a [Ca+2]i peak response of 8%ΔF/F (4/15) in 33% of 168 mast cells in the field of view. The mast cell response was abolished by the nerve blocker tetrododoxin, reduced by the Calcitonin Gene-Related Peptide receptor 1 antagonist BIBN-4096 and the Vasoactive Intestinal Peptide receptor antagonist PG97-269, but not by blockade of the neurokinin receptors 1–3. Conclusion: The findings revealed bidirectional signaling between mast cells and submucous neurons in human gut. In our macroscopically normal preparations a nerve to mast cell signaling was very prominent whereas a mast cell to nerve signaling was rather rare. PMID:29238306

Listeria monocytogenes Alters Mast Cell Phenotype, Mediator and Osteopontin Secretion in a Listeriolysin-Dependent Manner

PubMed Central

Jobbings, Catherine E.; Sandig, Hilary; Whittingham-Dowd, Jayde K.; Roberts, Ian S.; Bulfone-Paus, Silvia

2013-01-01

Whilst mast cells participate in the immune defence against the intracellular bacterium Listeria monocytogenes, there is conflicting evidence regarding the ability of L. monocytogenes to infect mast cells. It is known that the pore-forming toxin listeriolysin (LLO) is important for mast cell activation, degranulation and the release of pro-inflammatory cytokines. Mast cells, however, are a potential source of a wide range of cytokines, chemokines and other mediators including osteopontin, which contributes to the clearing of L. monocytogenes infections in vivo, although its source is unknown. We therefore aimed to resolve the controversy of mast cell infection by L. monocytogenes and investigated the extent of mediator release in response to the bacterium. In this paper we show that the infection of bone marrow-derived mast cells by L. monocytogenes is inefficient and LLO-independent. LLO, however, is required for calcium-independent mast cell degranulation as well as for the transient and selective downregulation of cell surface CD117 (c-kit) on mast cells. We demonstrate that in addition to the key pro-inflammatory cytokines TNF-α and IL-6, mast cells release a wide range of other mediators in response to L. monocytogenes. Osteopontin, IL-2, IL-4, IL-13 and granulocyte macrophage colony-stimulating factor (GM-CSF), and chemokines including CCL2, CCL3, CCL4 and CCL5 are released in a MyD88-dependent manner. The wide range of mediators released by mast cells in response to L. monocytogenes may play an important role in the recruitment and activation of a variety of immune cells in vivo. The cocktail of mediators, however, is unlikely to skew the immune response to a particular effector response. We propose that mast cells provide a hitherto unreported source of osteopontin, and may provide an important role in co-ordinating the immune response during Listeria infection. PMID:23460827

Promotion of mouse fibroblast collagen gene expression by mast cells stimulated via the Fc epsilon RI. Role for mast cell-derived transforming growth factor beta and tumor necrosis factor alpha

PubMed Central

1994-01-01

Chronic allergic diseases and other disorders associated with mast cell activation can also be associated with tissue fibrosis, but a direct link between mast cell mediator release and fibroblast collagen gene expression has not been established. Using in situ hybridization, we show that the elicitation of an IgE-dependent passive cutaneous anaphylaxis (PCA) reaction in mice results in a transient, but marked augmentation of steady state levels of type alpha-1 (I) collagen mRNA in the dermis. While peak levels of collagen mRNA expression in the skin are observed 16-24 h after mast cell activation, substantial numbers of dermal cells are strongly positive for collagen mRNA at 1 and 2 h after antigen challenge, before circulating inflammatory cells are recruited into the tissues. Furthermore, experiments in mast cell- reconstituted or genetically mast cell-deficient WBB6F1-W/Wv mice demonstrate that the increased expression of collagen mRNA at sites of PCA reactions is entirely mast cell dependent. In vitro studies show that the supernatants of mouse serosal mast cells activated via the Fc epsilon RI markedly increase type alpha-1 (I) collagen mRNA levels in mouse embryonic skin fibroblasts, and also upregulate collagen secretion by these cells. The ability of mast cell supernatants to induce increased steady state levels of collagen mRNA in mouse skin fibroblasts is markedly diminished by absorption with antibodies specific for either of two mast cell-derived cytokines, transforming growth factor beta (TGF-beta 1) or tumor necrosis factor alpha (TNF- alpha), and is eliminated entirely by absorption with antibodies against both cytokines. Taken together, these findings demonstrate that IgE-dependent mouse mast cell activation can induce a transient and marked increase in steady state levels of type alpha-1 (I) collagen mRNA in dermal fibroblasts and that mast cell-derived TGF-beta 1 and TNF-alpha importantly contribute to this effect. PMID:7964480

Mast Cell Proteases as Protective and Inflammatory Mediators

PubMed Central

Caughey, George H.

2014-01-01

Proteases are the most abundant class of proteins produced by mast cells. Many of these are stored in membrane-enclosed intracellular granules until liberated by degranulating stimuli, which include cross-linking of high affinity IgE receptor FcεRI by IgE bound to multivalent allergen. Understanding and separating the functions of the proteases is important because expression differs among mast cells in different tissue locations. Differences between laboratory animals and humans in protease expression also influence the degree of confidence with which results obtained in animal models of mast cell function can be extrapolated to humans. The inflammatory potential of mast cell proteases was the first aspect of their biology to be explored and has received the most attention, in part because some of them—notably tryptases and chymases—are biomarkers of local and systemic mast cell degranulation and anaphylaxis. Although some of the proteases indeed augment allergic inflammation and are potential targets for inhibition to treat asthma and related allergic disorders, they are protective and even anti-inflammatory in some settings. For example, mast cell tryptases may protect from serious bacterial lung infections and may limit the “rubor” component of inflammation caused by vasodilating neuropeptides in the skin. Chymases help to maintain intestinal barrier function and to expel parasitic worms, and may support blood pressure during anaphylaxis by generating angiotensin II. In other life-or-death examples, carboxypeptidase A3 and other mast cell peptidases limit systemic toxicity of endogenous peptides like endothelin and neurotensin during septic peritonitis, and inactivate venom-associated peptides. On the other hand, mast cell peptidase-mediated destruction of protective cytokines, like IL-6, can enhance mortality from sepsis. Peptidases released from mast cells also influence non-mast cell proteases, such as by activating matrix metalloproteinase cascades, which are important in responses to infection and resolution of tissue injury. Overall, mast cell proteases have a variety of roles—inflammatory and anti-inflammatory, protective and deleterious—in keeping with the increasingly well-appreciated contributions of mast cells in allergy, tissue homeostasis, and innate immunity. PMID:21713659

Comparison of Mast Cells and Inflammatory Cells within Periapical Lesions and Comparison of Degranulated Mast Cells Between Fibrous and Inflamed Area in Radicular Cysts: An Immunohistochemical Study

PubMed Central

Sood, Rahul; Akifuddin, Syed; Sidhu, Gagandeep Kaur; Khan, Nadia; Singla, Kapil

2014-01-01

Objective: The role of mast cells as the key effector of allergic inflammation, anaphylactic inflammatory reactions and in the pathogenesis of chronic inflammation, is well-known. The present study is adopted to compare mast cells and inflammatory cells within periapical granuloma and cysts and localize the mast cells and quantify their number in the periapical cysts so as to propose a role of mast cells in the pathogenesis of this lesion. Materials and Methods: Biopsy specimens of 30 periapical lesions were stained with hematoxylin–eosin, and immunohistochemical Mast Cell Tryptase from Bio SB (IHC detection system kit) antibody. The tryptase positive mast cells and mononuclear inflammatory cells were counted in 10 consecutive high power fields (100X) using the binocular microscope from Motic attached to a computer with Motic Advanced Images 3.2 software. Results: Comparative microscopic analysis indicated that periapical cyst shows more percentage of mast cells and less percentage of inflammatory cell than periapical granuloma (comparison of mean and standard deviation of total number of mast cells and inflammatory cells, mast cells 3.15±1.39 in the granuloma group and 4.43±1.91in the cyst group, inflammatory cells, 67.11±1.2 in the granuloma group and 52.66±0.8 in the cyst group). Numerous degranulated mast cells were observed in the fibrous wall than the inflammatory infiltrate of the periapical cysts. The mean and standard deviation of degranulated mast cells between the inflammatory and fibrous zone within the cyst group, being 0.95±1.10 and1.68±1.34 respectively. The values varied significantly between the two zones. Conclusion: The number of inflammatory cells in the cyst group is less than periapical granuloma and total number of mast cells in the cyst group is more as compared to periapical granuloma. The degranulated cells were quantified and they were higher in the fibrous area of the cysts than the inflammatory zone. This study could support the fact that the various mediators released on degranulation play a role in the connective tissue remodeling, chronicity and expansion of the periapical lesion. PMID:25654034

Size Scales for Thermal Inhomogeneities in Mars' Atmosphere Surface Layer: Mars Pathfinder

NASA Technical Reports Server (NTRS)

Mihalov, John D.; Haberle, Robert M.; Seiff, Alvin; Murphy, James R.; Schofield, John T.; DeVincenzi, Donald L. (Technical Monitor)

2000-01-01

Atmospheric temperature measurement at three heights with thin wire thermocouples on the 1.1 m Mars Pathfinder meteorology must allow estimates of the integral scale of the atmospheric thermal turbulence during an 83 sol period that begins in the summer. The integral scale is a measure for regions of perturbations. In turbulent media that roughly characterizes locations where the perturbations are correlated. Excluding some to intervals with violent excursions of the mean temperatures, integral scale values are found that increase relatively rapidly from a few tenths meters or less near down to several meters by mid-morning. During mid-morning, the diurnal and shorter time scale wind direction variations often place the meteorology mast in the thermal wake of the Lander.

Spatial correlation of atmospheric wind at scales relevant for large scale wind turbines

NASA Astrophysics Data System (ADS)

Bardal, L. M.; Sætran, L. R.

2016-09-01

Wind measurements a short distance upstream of a wind turbine can provide input for a feedforward wind turbine controller. Since the turbulent wind field will be different at the point/plane of measurement and the rotor plane the degree of correlation between wind speed at two points in space both in the longitudinal and lateral direction should be evaluated. This study uses a 2D array of mast mounted anemometers to evaluate cross-correlation of longitudinal wind speed. The degree of correlation is found to increase with height and decrease with atmospheric stability. The correlation is furthermore considerably larger for longitudinal separation than for lateral separation. The integral length scale of turbulence is also considered.

KSC-2009-1562

NASA Image and Video Library

2009-02-12

CAPE CANAVERAL, Fla. – The faint sunrise sky over NASA's Kennedy Space Center casts the newly erected lightning towers on Launch Pad 39B in silhouette. They surround the fixed and rotating service structures at center that have served the Space Shuttle Program. The new lightning protection system is being built for the Constellation Program and Ares/Orion launches. Each of the towers is 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-1001

NASA Image and Video Library

2009-01-02

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, a crane completes construction of one of the towers in the new lightning protection system for the Constellation Program and Ares/Orion launches. Other towers are being constructed at left and behind the service structures on the pad. Each of the three new lightning towers will be 500 feet tall with an additional 100-foot fiberglass mast atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Troy Cryder

Initial response of individual soft mast-producing plants to different forest regeneration methods in the Ouachita Mountains

Treesearch

Roger W. Perry; Ronald E. Thill; Philip A. Tappe; David G. Peitz

2004-01-01

Abstract - Recent policy changes have eliminated clearcutting as the primary pine regeneration method on Federal lands in the Southern United States. However, the effects of alternative natural regeneration methods on soft mast production are unknown. We compared plant coverage and mast production of 37 soft mast-producing plants among four...

[SONG's theory on mast cells and meridian-acupoint and its research prospect].

PubMed

Li, Yongming

2016-10-12

The historical origin of researches regarding acupuncture and mast cells (MCs) is reviewed, and the hypothesis that dermal MCs might be correlated with the acupuncture phenomena proposed by SONG Jimei in 1977 is introduced. This hypothesis, for the first time, suggests MCs could be the cellular basis of meridian sensation and arrival of qi ( deqi ) of acupoints. With independent tests of several research institutes, currently sufficient evidences prove the scientific values of SONG 's theory as well as its potential values for the basic research and clinical practice of acupuncture. It is reported recently that MCs might receive signals from central nerve system and acupoint stimulation, showing cross-talk effects, therefore, MCs can be sensitized at acupoints. In this paper, with a review of 40-year research evidence, 15 biological characteristics regarding mast cells and acupuncture phenomena are identified, in the meanwhile, 10 key questions and research direction, including the distribution of MCs in skin and its general relationship with meridian-acupoint, etc. are proposed.

The stem cell growth factor receptor KIT is not expressed on interstitial cells in bladder.

PubMed

Gevaert, Thomas; Ridder, Dirk De; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Aa, Frank Van Der; Pintelon, Isabel; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Neuhaus, Jochen

2017-06-01

The mast/stem cell growth factor receptor KIT has long been assumed to be a specific marker for interstitial cells of Cajal (ICC) in the bladder, with possible druggable perspectives. However, several authors have challenged the presence of KIT + ICC in recent years. The aim of this study was therefore to attempt to clarify the conflicting reports on KIT expression in the bladder of human beings, rat, mouse and guinea pig and to elucidate the possible role of antibody-related issues and interspecies differences in this matter. Fresh samples were obtained from human, rat, mouse and guinea pig cystectomies and processed for single/double immunohistochemistry/immunofluorescence. Specific antibodies against KIT, mast cell tryptase (MCT), anoctamin-1 (ANO1) and vimentin were used to characterize the cell types expressing KIT. Gut (jejunum) tissue was used as an external antibody control. Our results revealed KIT expression on mast cells but not on ICC in human, rat, mouse and guinea pig bladder. Parallel immunohistochemistry showed KIT expression on ICC in human, rat, mouse and guinea pig gut, which confirmed the selectivity of the KIT antibody clones. In conclusion, we have shown that KIT + cells in human, rat, mouse and guinea pig bladder are mast cells and not ICC. The present report is important as it opposes the idea that KIT + ICC are present in bladder. In this perspective, functional concepts of KIT + ICC being involved in sensory and/or motor aspects of bladder physiology should be revised. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Immunohistochemical expression of mast cell tryptase in giant cell fibroma and inflammatory fibrous hyperplasia of the oral mucosa.

PubMed

Santos, Pedro Paulo de Andrade; Nonaka, Cassiano Francisco Weege; Pinto, Leão Pereira; de Souza, Lélia Batista

2011-03-01

This study analysed the immunohistochemical expression of mast cell tryptase in giant cell fibromas (GCFs). In addition, the possible interaction of mast cells with stellate giant cells, as well as their role in fibrosis and tumour progression, was investigated. For this purpose, the results were compared with cases of inflammatory fibrous hyperplasia (IFH) and normal oral mucosa. Thirty cases of GCF, 30 cases of IFH and 10 normal mucosa specimens used as control were selected. Immunoreactivity of mast cells to the anti-tryptase antibody was analysed quantitatively in the lining epithelium and in connective tissue. In the epithelial component (p=0.250) and connective tissue (p=0.001), the largest mean number of mast cells was observed in IFHs and the smallest mean number in GCFs. In connective tissue, the mean percentage of degranulated mast cells was higher in GCFs than in IFHs and normal mucosa specimens (p<0.001). Analysis of the percentage of degranulated mast cells in areas of fibrosis and at the periphery of blood vessels also showed a larger mean number in GCFs compared to IFHs and normal mucosa specimens (p<0.001). The percent interaction between mast cells and stellate giant cells in GCFs was 59.62%. In conclusion, although mast cells were less numerous in GCFs, the cells exhibited a significant interaction with stellate giant cells present in these tumours. In addition, the results suggest the involvement of mast cells in the induction of fibrosis and modulation of endothelial cell function in GCFs. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Hepatic mucosal mast cell hyperplasia in rats with secondary biliary cirrhosis.

PubMed

Rioux, K P; Sharkey, K A; Wallace, J L; Swain, M G

1996-04-01

Mast cells have been shown to play a role in many chronic inflammatory and fibrotic disorders. However, their possible contribution to the pathological changes that occur in liver cirrhosis is unknown. To explore this, we examined whether changes in hepatic mast cell number and mediator content were associated with fibrotic changes in experimental biliary cirrhosis. Rats were studied 7, 14, or 21 days after bile duct resection (BDR). Hepatic mast cells were identified by histochemical and immunohistochemical stains. Rat mast cell protease II (RMCP-II), a marker of mast cell degranulation, was measured in liver by enzyme-linked immunosorbent assay. Hepatic collagen deposition was assessed by Sirius Red F3BA staining. In day 21 BDR rats, there was a one- to twofold increase (P < .001) in the number of hepatic mast cells, but this was not observed in day 7 or 14 BDR rats. Mild fibrotic changes were noted in BDR rat livers as early as 7 days after induction of cholestasis. Significant expansion and organization of fibrous tissue had occurred in day 14 BDR rats which progressed to bridging fibrosis by day 21. Liver RMCP-II levels were decreased by 50 percent (P < .05) and mast cell degranulation was apparent as shown by histamine immunostaining. These results suggest that hepatic mast cell hyperplasia and degranulation occur during prolonged cholestasis in the rat. Although these changes do not correlate with the onset of hepatic fibrosis, they do occur at a time during which there is significant deposition and organization extracellular matrix elements. Hepatic mast cells, by releasing profibrogenic mediators, may contribute to fibrotic changes in biliary cirrhosis.

Masting behaviour in a Mediterranean pine tree alters seed predator selection on reproductive output.

PubMed

Moreira, X; Abdala-Roberts, L; Zas, R; Merlo, E; Lombardero, M J; Sampedro, L; Mooney, K A

2016-11-01

Context-dependency in species interactions is widespread and can produce concomitant patterns of context-dependent selection. Masting (synchronous production of large seed crops at irregular intervals by a plant population) has been shown to reduce seed predation through satiation (reduction in rates of seed predation with increasing seed cone output) and thus represents an important source of context-dependency in plant-animal interactions. However, the evolutionary consequences of such dynamics are not well understood. Here we describe masting behaviour in a Mediterranean model pine species (Pinus pinaster) and present a test of the effects of masting on selection by seed predators on reproductive output. We predicted that masting, by enhancing seed predator satiation, could in turn strengthen positive selection by seed predators for larger cone output. For this we collected six-year data (spanning one mast year and five non-mast years) on seed cone production and seed cone predation rates in a forest genetic trial composed by 116 P. pinaster genotypes. Following our prediction, we found stronger seed predator satiation during the masting year, which in turn led to stronger seed predator selection for increased cone production relative to non-masting years. These findings provide evidence that masting can alter the evolutionary outcome of plant-seed predator interactions. More broadly, our findings highlight that changes in consumer responses to resource abundance represent a widespread mechanism for predicting and understanding context dependency in plant-consumer evolutionary dynamics. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

Mast cell number, substance P and vasoactive intestinal peptide in irritable bowel syndrome with diarrhea.

PubMed

Sohn, Won; Lee, Oh Young; Lee, Sang Pyo; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon; Sim, Jongmin; Jang, Ki-Seok

2014-01-01

Recent studies have shown that mast cells play an important role in irritable bowel syndrome (IBS). We investigated the relationship between mast cells and the gut hormones substance P and vasoactive intestinal peptide (VIP) in irritable bowel syndrome with diarrhea (IBS-D). Colonoscopic biopsies were performed on the rectal mucosa of 43 subjects (IBS-D patients: 22, healthy volunteers: 21) diagnosed according to the Rome III criteria. Mast cells, and substance P & VIP were evaluated by quantitative immunohistology and image analysis. Mast cells were counted as tryptase-positive cells in the lamina propria, and substance P and VIP levels were expressed as percentages of total areas of staining. Mast cell counts were higher in IBS-D patients than healthy volunteers (9.6 ± 3.3 vs. 5.7 ± 2.5/high power field (HPF), p < 0.01). Substance P was also elevated (0.11 ± 0.08% vs. 0.03 ± 0.02 %, p < 0.01) while VIP was only high in women with IBS-D. Mast cell counts were positively correlated with levels of substance P & VIP in women but not men (women: r = 0.625, p < 0.01 for substance P and r = 0.651, p < 0.01 for VIP). However, mast cell counts were not correlated with IBS symptoms including abdominal pain. Mast cells are activated leading to the raised levels of substance P & VIP in IBS-D patients. However, the correlation between mast cells and levels of substance P & VIP differs according to gender.

Eosinophilic Esophagitis: Relevance of Mast Cell Infiltration.

PubMed

Strasser, Daniel S; Seger, Shanon; Bussmann, Christian; Pierlot, Gabin M; Groenen, Peter M A; Stalder, Anna K; Straumann, Alex

2018-05-17

Eosinophilic esophagitis (EoE) is a chronic-inflammatory disease characterized clinically by symptoms of esophageal dysfunction and histopathologically by a prominent eosinophilic inflammation. Despite eosinophils having histologically a pre-dominant position, their role in the immunopathogenesis of the disease is still questionable. Several other inflammatory cells are involved and may play a critical role as well. The purpose of this study was to characterize the mast cell infiltration, and to correlate it with clinical state of EoE. Using immunohistochemistry and quantitative morphometry, we extensively investigated eosinophils and mast cells in esophageal biopsies from patients with active EoE and from patients with EoE in remission, and compared the findings with healthy individuals. In EoE, epithelium and lamina propria were similarly infiltrated with eosinophils. In contrast, mast cells infiltration was limited to the epithelium, displaying a localized immune response. Interestingly, whereas epithelial mast cells and eosinophils were high in active EoE, some patients in remission e.g. normalized epithelial eosinophils, showed remaining high numbers of mast cells. Patient clustering supported 2 groups of patients in clinical remission, differentiating based on presence or absence of epithelial mast cells. Active EoE is characterized - in addition to the well-known tissue eosinophilia by a marked epithelium-restricted mast cell infiltration. Of interest, in a subgroup of patients, mast cell infiltration persisted despite clinical remission. To elucidate the clinical consequence of persistent epithelial mast cells infiltration further studies are required following patients in clinical remission longitudinally. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Immunophenotypic characterization of bone marrow mast cells in mastocytosis and other mast cell disorders.

PubMed

Sánchez-Muñoz, Laura; Teodósio, Cristina; Morgado, José M; Escribano, Luis

2011-01-01

Mastocytosis is a term used to designate a heterogeneous group of disorders characterized by an abnormal proliferation and accumulation of mast cells (MCs) in one or multiple tissues including skin, bone marrow (BM), liver, spleen, and lymph nodes, among others. Recent advances in our understanding of mast cell biology and disease resulted in the identification of important differences in the expression of mast cell surface antigens between normal and neoplastic mast cells. Most notably, detection of aberrant expression of CD25 and CD2 on the surface of neoplastic mast cells but not on their normal counterparts lead to the inclusion of this immunophenotypic abnormality in the World Health Organization diagnostic criteria for systemic mastocytosis. Aberrant mast cell surface marker expression can be detected in the bone marrow aspirate by flow cytometry, even in patients lacking histopathologically detectable aggregates of mast cells in bone marrow biopsy sections. These aberrant immunophenotypic features are of great relevance for the assessment of tissue involvement in mastocytosis with consequences in the diagnosis, classification, and follow-up of the disease and in its differential diagnosis with other entities. In this chapter, we provide the reader with information for the objective and reproducible identification of pathologic MCs by using quantitative multiparametric flow cytometry, for their phenotypic characterization, and the criteria currently used for correct interpretation of the immunophenotypic results obtained. Copyright © 2011 Elsevier Inc. All rights reserved.

Environmentally relevant metal and transition metal ions enhance Fc epsilon RI-mediated mast cell activation.

PubMed Central

Walczak-Drzewiecka, Aurelia; Wyczólkowska, Janina; Dastych, Jaroslaw

2003-01-01

Upon contact with allergen, sensitized mast cells release highly active proinflammatory mediators. Allergen-mediated mast cell activation is an important mechanism in the pathogenesis of atopic asthma. Asthmatic patients are especially susceptible to air pollution. Epidemiologic studies found a positive correlation between severity of symptoms among asthmatic patients and the level of particulate matter (PM) in the air. Among the constituents of PM are metals and transition metals, which could mediate some of its adverse effects on human health. We sought to determine the effect of metal and transition metal ions on allergen-mediated mast cell activation. We observed that several metal and transition metal ions activated mast cells and enhanced allergen-mediated mast cell activation. Thus, Al(3+), Cd(2+), and Sr(2+) induced release of granule-associated N-acetyl-ss-d-hexosaminidase, and Al(3+) and Ni(2+) enhanced antigen-mediated release. Metal and transition metal ions also induced significant secretion of interleukin (IL)-4 and increased antigen-mediated IL-4 secretion in mast cells. These effects of metal and transition metal ions on mast cells were observed at concentrations that do not result in direct cytotoxicity and might be relevant for environmental exposure. Thus, metals and transition metals could increase the level of allergen-mediated mast cell activation, which might be one of the mechanisms mediating exacerbation of allergen-driven asthma symptoms by air pollution. PMID:12727598

Changing the threshold-Signals and mechanisms of mast cell priming.

PubMed

Halova, Ivana; Rönnberg, Elin; Draberova, Lubica; Vliagoftis, Harissios; Nilsson, Gunnar P; Draber, Petr

2018-03-01

Mast cells play a key role in allergy and other inflammatory diseases involving engagement of multivalent antigen with IgE bound to high-affinity IgE receptors (FcεRIs). Aggregation of FcεRIs on mast cells initiates a cascade of signaling events that eventually lead to degranulation, secretion of leukotrienes and prostaglandins, and cytokine and chemokine production contributing to the inflammatory response. Exposure to pro-inflammatory cytokines, chemokines, bacterial and viral products, as well as some other biological products and drugs, induces mast cell transition from the basal state into a primed one, which leads to enhanced response to IgE-antigen complexes. Mast cell priming changes the threshold for antigen-mediated activation by various mechanisms, depending on the priming agent used, which alone usually do not induce mast cell degranulation. In this review, we describe the priming processes induced in mast cells by various cytokines (stem cell factor, interleukins-4, -6 and -33), chemokines, other agents acting through G protein-coupled receptors (adenosine, prostaglandin E 2 , sphingosine-1-phosphate, and β-2-adrenergic receptor agonists), toll-like receptors, and various drugs affecting the cytoskeleton. We will review the current knowledge about the molecular mechanisms behind priming of mast cells leading to degranulation and cytokine production and discuss the biological effects of mast cell priming induced by several cytokines. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mast cells in Canine parvovirus-2-associated enteritis with crypt abscess.

PubMed

Woldemeskel, M W; Saliki, J T; Blas-Machado, U; Whittington, L

2013-11-01

The role of mast cells (MCs) in allergic reactions and parasitic infections is well established. Their involvement in host immune response against bacterial and viral infections is reported. In this study, investigation is made to determine if MCs are associated with Canine parvovirus-2 (CPV-2)-induced enteritis with crypt abscess (ECA). Mast cell count (MCC) was made on toluidine blue-stained intestinal sections from a total of 34 dogs. These included 16 dogs exhibiting ECA positive for CPV-2 and negative for Canine distemper virus and Canine coronavirus by immunohistochemistry and fluorescent antibody test, 12 dogs with inflammatory bowel disease (IBD), and 6 non-ECA/non-IBD (control) dogs. The average total MCC per high-power field in ECA (40.8 ± 2.2) and IBD (24.7 ± 2.1) was significantly higher (P < .05) than in the control (3.4 ± 0.6). Although not significant (P > .05), MCC was also higher in ECA than in IBD. The present study for the first time has documented significantly increased MCs in CPV-2-associated ECA as was previously reported for IBD, showing that MCs may also play an important role in CPV-2-associated ECA. Further studies involving more CPV-infected dogs are recommended to substantiate the findings.

30 CFR 56.7051 - Loose objects on the mast or drill platform.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Loose objects on the mast or drill platform. 56... Drilling and Rotary Jet Piercing Drilling § 56.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the mast or drill platform. ...

Seasonal Mast Availability for Wildlife in the Piedmont Region of Georgia

Treesearch

John W. Edwards; David C. Guynn; Susan C. Loeb

1993-01-01

We measured mast production by traditional and buffer species for 2 years on the Piedmont National Wildlife Refuge in Georgia. Our objectives were to determine how these two types varied on a seasonal, annual, and habitat basis. Mast from buffer species was more frequent and diverse than that from traditional mast producers. Our findings suggest that although...

53. VIEW FROM FLOOR OF MAST TRENCH SHOWING BASE OF ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

53. VIEW FROM FLOOR OF MAST TRENCH SHOWING BASE OF ERECT UMBILICAL MAST. AIR-CONDITIONING DUCTS VISIBLE ON RIGHT SIDE OF MAST. HYDRAULIC ACTUATOR ARMS FOR OPENING TRENCH DOORS VISIBLE ON LEFT SIDE OF PHOTO. 'DOOR STOP' PEDESTAL IN FOREGROUND. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

30 CFR 56.7051 - Loose objects on the mast or drill platform.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Loose objects on the mast or drill platform. 56... Drilling and Rotary Jet Piercing Drilling § 56.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the mast or drill platform. ...

30 CFR 56.7051 - Loose objects on the mast or drill platform.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Loose objects on the mast or drill platform. 56... Drilling and Rotary Jet Piercing Drilling § 56.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the mast or drill platform. ...

Introduction to the MAST Program. MAS-100. Waste Isolation Division (WID). Management and Supervisor Training (MAST) Program.

ERIC Educational Resources Information Center

Westinghouse Electric Corp., Carlsbad, NM.

This module is part of a set of management and supervisor training (MAST) materials developed by the Department of Energy for the Waste Isolation Division. Its stated purpose is to provide participants with knowledge and skills necessary to take full advantage of the MAST learning experience. The module contains program guidelines, sample…

Initial Effects of Reproduction Cutting Treatments on Residual Hard Mast Production in the Ouachita Mountains

Treesearch

Roger W. Perry; Ronald E. Thill

2003-01-01

We compared indices of total hard mast production (oak and hickory combined) in 20, second-growth, pine-hardwood stands under five treatments to determine the effects of different reproduction treatments on mast production in the Ouachita Mountains. We evaluated mast production in mature unharvested controls and stands under four reproduction cutting methods (single-...

Acute infection with the intestinal parasite Trichuris muris has long-term consequences on mucosal mast cell homeostasis and epithelial integrity.

PubMed

Sorobetea, Daniel; Holm, Jacob Bak; Henningsson, Henrietta; Kristiansen, Karsten; Svensson-Frej, Marcus

2017-02-01

A hallmark of parasite infection is the accumulation of innate immune cells, notably granulocytes and mast cells, at the site of infection. While this is typically viewed as a transient response, with the tissue returning to steady state once the infection is cleared, we found that mast cells accumulated in the large-intestinal epithelium following infection with the nematode Trichuris muris and persisted at this site for several months after worm expulsion. Mast cell accumulation in the epithelium was associated with the induction of type-2 immunity and appeared to be driven by increased maturation of local progenitors in the intestinal lamina propria. Furthermore, we also detected increased local and systemic levels of the mucosal mast cell protease MCPt-1, which correlated highly with the persistent epithelial mast cell population. Finally, the mast cells appeared to have striking consequences on epithelial barrier integrity, by regulation of gut permeability long after worm expulsion. These findings highlight the importance of mast cells not only in the early phases of infection but also at later stages, which has functional implications on the mucosal tissue. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Substance P enhances electrical field stimulation-induced mast cell degranulation in rat trachea.

PubMed

Hua, X Y; Back, S M; Tam, E K

1996-06-01

We previously demonstrated in an ex vivo rat tracheal model that chymotryptic activity is an index of mast cell degranulation and that substance P (SP) and electrical field stimulation (EFS) synergistically degranulate mucosal and connective tissue mast cells. In the current study, we found that the facilitatory effect of SP was apparent at concentrations as low as 10(-9) M. This effect was mimicked by 10(-7) M neurokinin A or by 10(-6) M capsaicin and was blocked by the NK1 receptor antagonist CP-96,345. SP + EFS-induced mast cell secretion was significantly attenuated by 10(-6) M tetrodotoxin. The response was also attenuated in tracheas from rats in which sensory nerves had been depleted by systemic pretreatment with capsaicin or in which sympathetic nerves had been depleted by systemic pretreatment with 6-hydroxy-dopamine. Atropine (10(-6) M) or indomethacin (10(-5) M) also attenuated SP + EFS-induced mast cell secretion. Our findings suggest the importance of a sensitizing rather than a direct stimulating effect of SP on mast cell degranulation. SP may increase the sensitivity of mast cells to EFS-discharged mediators or facilitate the release of mast cell-stimulating mediators from autonomic nerves.

Mast cells in atherosclerotic cardiovascular disease - Activators and actions.

PubMed

Kovanen, Petri T; Bot, Ilze

2017-12-05

Mast cells are potent actors involved in inflammatory reactions in various tissues, including both in the intimal and the adventitial layers of atherosclerotic arteries. In the arterial intima, the site of atherogenesis, mast cells are activated to degranulate, and thereby triggered to release an abundance of preformed inflammatory mediators, notably histamine, heparin, neutral proteases and cytokines stored in their cytoplasmic secretory granules. Depending on the stimulus, mast cell activation may also launch prolonged synthesis and secretion of single bioactive molecules, such as cytokines and derivatives of arachidonic acid. The mast cell-derived mediators may impede the functions of different types of cells present in atherosclerotic lesions, and also compromise the structural and functional integrity of the intimal extracellular matrix. In the adventitial layer of atherosclerotic coronary arteries, mast cells locate next to peptidergic sensory nerve fibers, which, by releasing neuropeptides may activate mast cells to release vasoactive compounds capable of triggering local vasoconstriction. The concerted actions of arterial mast cells have the potential to contribute to the initiation and progression of atherosclerosis, and ultimately to destabilization and rupture of an advanced atherosclerotic plaque with ensuing atherothrombotic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Mast Cell, the Neglected Member of the Tumor Microenvironment: Role in Breast Cancer.

PubMed

Aponte-López, Angélica; Fuentes-Pananá, Ezequiel M; Cortes-Muñoz, Daniel; Muñoz-Cruz, Samira

2018-01-01

Mast cells are unique tissue-resident immune cells that secrete a diverse array of biologically active compounds that can stimulate, modulate, or suppress the immune response. Although mounting evidence supports that mast cells are consistently infiltrating tumors, their role as either a driving or an opposite force for cancer progression is still controversial. Particularly, in breast cancer, their function is still under discussion. While some studies have shown a protective role, recent evidence indicates that mast cells enhance blood and lymphatic vessel formation. Interestingly, one of the most important components of the mast cell cargo, the serine protease tryptase, is a potent angiogenic factor, and elevated serum tryptase levels correlate with bad prognosis in breast cancer patients. Likewise, histamine is known to induce tumor cell proliferation and tumor growth. In agreement, mast cell depletion reduces the size of mammary tumors and metastasis in murine models that spontaneously develop breast cancer. In this review, we will discuss the evidence supporting protumoral and antitumoral roles of mast cells, emphasizing recent findings placing mast cells as important drivers of tumor progression, as well as the potential use of these cells or their mediators as therapeutic targets.

Nonlinear Modeling of Joint Dominated Structures

NASA Technical Reports Server (NTRS)

Chapman, J. M.

1990-01-01

The development and verification of an accurate structural model of the nonlinear joint-dominated NASA Langley Mini-Mast truss are described. The approach is to characterize the structural behavior of the Mini-Mast joints and struts using a test configuration that can directly measure the struts' overall stiffness and damping properties, incorporate this data into the structural model using the residual force technique, and then compare the predicted response with empirical data taken by NASA/LaRC during the modal survey tests of the Mini-Mast. A new testing technique, referred to as 'link' testing, was developed and used to test prototype struts of the Mini-Masts. Appreciable nonlinearities including the free-play and hysteresis were demonstrated. Since static and dynamic tests performed on the Mini-Mast also exhibited behavior consistent with joints having free-play and hysteresis, nonlinear models of the Mini-Mast were constructed and analyzed. The Residual Force Technique was used to analyze the nonlinear model of the Mini-Mast having joint free-play and hysteresis.

Inter-annual and decadal changes in teleconnections drive continental-scale synchronization of tree reproduction.

PubMed

Ascoli, Davide; Vacchiano, Giorgio; Turco, Marco; Conedera, Marco; Drobyshev, Igor; Maringer, Janet; Motta, Renzo; Hacket-Pain, Andrew

2017-12-20

Climate teleconnections drive highly variable and synchronous seed production (masting) over large scales. Disentangling the effect of high-frequency (inter-annual variation) from low-frequency (decadal trends) components of climate oscillations will improve our understanding of masting as an ecosystem process. Using century-long observations on masting (the MASTREE database) and data on the Northern Atlantic Oscillation (NAO), we show that in the last 60 years both high-frequency summer and spring NAO, and low-frequency winter NAO components are highly correlated to continent-wide masting in European beech and Norway spruce. Relationships are weaker (non-stationary) in the early twentieth century. This finding improves our understanding on how climate variation affects large-scale synchronization of tree masting. Moreover, it supports the connection between proximate and ultimate causes of masting: indeed, large-scale features of atmospheric circulation coherently drive cues and resources for masting, as well as its evolutionary drivers, such as pollination efficiency, abundance of seed dispersers, and natural disturbance regimes.

Controversial role of mast cells in skin cancers.

PubMed

Varricchi, Gilda; Galdiero, Maria R; Marone, Giancarlo; Granata, Francescopaolo; Borriello, Francesco; Marone, Gianni

2017-01-01

Cancer development is a multistep process characterized by genetic and epigenetic alterations during tumor initiation and progression. The stromal microenvironment can promote tumor development. Mast cells, widely distributed throughout all tissues, are a stromal component of many solid and haematologic tumors. Mast cells can be found in human and mouse models of skin cancers such as melanoma, basal and squamous cell carcinomas, primary cutaneous lymphomas, haemangiomas and Merkel cell carcinoma. However, human and animal studies addressing potential functions of mast cells and their mediators in skin cancers have provided conflicting results. In several studies, mast cells play a pro-tumorigenic role, whereas in others, they play an anti-tumorigenic role. Other studies have failed to demonstrate a clear role for tumor-associated mast cells. Many unanswered questions need to be addressed before we understand whether tumor-associated mast cells are adversaries, allies or simply innocent bystanders in different types and subtypes of skin cancers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Carbonic anhydrase enzymes regulate mast cell–mediated inflammation

PubMed Central

Soteropoulos, Patricia

2016-01-01

Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine–mediated inflammation through their enhanced ability to develop into mast cells. In this study, we show that carbonic anhydrase (Car) enzymes are up-regulated in type 2–associated progenitor cells and demonstrate that Car enzyme inhibition is sufficient to prevent mouse mast cell responses and inflammation after Trichinella spiralis infection or the induction of food allergy–like disease. Further, we used CRISPR/Cas9 technology and illustrate that genetically editing Car1 is sufficient to selectively reduce mast cell development. Finally, we demonstrate that Car enzymes can be targeted to prevent human mast cell development. Collectively, these experiments identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that Car enzyme inhibitors may possess therapeutic potential that can be used to treat mast cell–mediated inflammation. PMID:27526715

Brain mast cells link the immune system to anxiety-like behavior

PubMed Central

Nautiyal, Katherine M.; Ribeiro, Ana C.; Pfaff, Donald W.; Silver, Rae

2008-01-01

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links. PMID:19004805

Brain mast cells link the immune system to anxiety-like behavior.

PubMed

Nautiyal, Katherine M; Ribeiro, Ana C; Pfaff, Donald W; Silver, Rae

2008-11-18

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient Kit(W-sh/W-sh) (sash(-/-)) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

Diverse exocytic pathways for mast cell mediators.

PubMed

Xu, Hao; Bin, Na-Ryum; Sugita, Shuzo

2018-04-17

Mast cells play pivotal roles in innate and adaptive immunities but are also culprits in allergy, autoimmunity, and cardiovascular diseases. Mast cells respond to environmental changes by initiating regulated exocytosis/secretion of various biologically active compounds called mediators (e.g. proteases, amines, and cytokines). Many of these mediators are stored in granules/lysosomes and rely on intricate degranulation processes for release. Mast cell stabilizers (e.g. sodium cromoglicate), which prevent such degranulation processes, have therefore been clinically employed to treat asthma and allergic rhinitis. However, it has become increasingly clear that different mast cell diseases often involve multiple mediators that rely on overlapping but distinct mechanisms for release. This review illustrates existing evidence that highlights the diverse exocytic pathways in mast cells. We also discuss strategies to delineate these pathways so as to identify unique molecular components which could serve as new drug targets for more effective and specific treatments against mast cell-related diseases. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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

Amagai, Yosuke; Tanaka, Akane; Ohmori, Keitaro

Much is known regarding participations of mast cells with innate and acquired immunity by secreting various cytokines and chemical mediators. However, details of mast cell biology still remain unclear. In this study, we successfully established a novel growth factor-independent mast cell line (MPT-1) derived from canine mast cell tumor. MPT-1 cells manifested factor-independent proliferation as floating cells containing a large amount of histamine, as well as chymase-like dog mast cell protease 3, in cytosolic granules. Particularly, MPT-1 cells expressed high-affinity IgE receptors (Fc{epsilon}RI) and wild-type c-kit receptors. Degranulation of MPT-1 cells was induced not only by stimulation with calcium ionophoremore » but also by cross-linkage of the surface IgE. Given that MPT-1 is the first mast cell line with Fc{epsilon}RI which has no c-kit mutations, MPT-1 cells may provide great contribution for investigation of IgE-mediated activation mechanisms of mast cells, leading to development of effective treatment for allergic disorders.« less

A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology.

PubMed

Grassberger, M; Baumruker, T; Enz, A; Hiestand, P; Hultsch, T; Kalthoff, F; Schuler, W; Schulz, M; Werner, F J; Winiski, A; Wolff, B; Zenke, G

1999-08-01

SDZ ASM 981, a novel ascomycin macrolactam derivative, has high anti-inflammatory activity in animal models of allergic contact dermatitis and shows clinical efficacy in atopic dermatitis, allergic contact dermatitis and psoriasis, after topical application. Here we report on the in vitro activities of this promising new drug. SDZ ASM 981 inhibits the proliferation of human T cells after antigen-specific or non-specific stimulation. It downregulates the production of Th1 [interleukin (IL)-2, interferon-gamma] and Th2 (IL-4, IL-10) type cytokines after antigen-specific stimulation of a human T-helper cell clone isolated from the skin of an atopic dermatitis patient. SDZ ASM 981 inhibits the phorbol myristate acetate/phytohaemagglutinin-stimulated transcription of a reporter gene coupled to the human IL-2 promoter in the human T-cell line Jurkat and the IgE/antigen-mediated transcription of a reporter gene coupled to the human tumour necrosis factor (TNF)-alpha promoter in the murine mast-cell line CPII. It does not, however, affect the human TNF-alpha promoter controlled transcription of a reporter gene in a murine dendritic cell line (DC18 RGA) after stimulation via the FcgammaRIII receptor. SDZ ASM 981 also prevents the release of preformed pro-inflammatory mediators from mast cells, as shown in the murine cell line CPII after stimulation with IgE/antigen. In summary, these results demonstrate that SDZ ASM 981 is a specific inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro.

A new humanized in vivo model of KIT D816V+ advanced systemic mastocytosis monitored using a secreted luciferase

PubMed Central

Bibi, Siham; Zhang, Yanyan; Hugonin, Caroline; Mangean, Mallorie Depond; He, Liang; Wedeh, Ghaith; Launay, Jean-Marie; Van Rijn, Sjoerd; Würdinger, Thomas; Louache, Fawzia; Arock, Michel

2016-01-01

Systemic mastocytosis are rare neoplasms characterized by accumulation of mast cells in at least one internal organ. The majority of systemic mastocytosis patients carry KIT D816V mutation, which activates constitutively the KIT receptor. Patient with advanced forms of systemic mastocytosis, such as aggressive systemic mastocytosis or mast cell leukemia, are poorly treated to date. Unfortunately, the lack of in vivo models reflecting KIT D816V+ advanced disease hampers pathophysiological studies and preclinical development of new therapies for such patients. Here, we describe a new in vivo model of KIT D816V+ advanced systemic mastocytosis developed by transplantation of the human ROSAKIT D816V-Gluc mast cell line in NOD-SCID IL-2R g−/− mice, using Gaussia princeps luciferase as a reporter. Intravenous injection of ROSAKIT D816V-Gluc cells led, in 4 weeks, to engraftment in all injected primary recipient mice. Engrafted cells were found at high levels in bone marrow, and at lower levels in spleen, liver and peripheral blood. Disease progression was easily monitored by repeated quantification of Gaussia princeps luciferase activity in peripheral blood. This quantification evidenced a linear relationship between the number of cells injected and the neoplastic mast cell burden in mice. Interestingly, the secondary transplantation of ROSAKIT D816V-Gluc cells increased their engraftment capability. To conclude, this new in vivo model mimics at the best the features of human KIT D816V+ advanced systemic mastocytosis. In addition, it is a unique and convenient tool to study the kinetics of the disease and the potential in vivo activity of new drugs targeting neoplastic mast cells. PMID:27783996

A new humanized in vivo model of KIT D816V+ advanced systemic mastocytosis monitored using a secreted luciferase.

PubMed

Bibi, Siham; Zhang, Yanyan; Hugonin, Caroline; Mangean, Mallorie Depond; He, Liang; Wedeh, Ghaith; Launay, Jean-Marie; Van Rijn, Sjoerd; Würdinger, Thomas; Louache, Fawzia; Arock, Michel

2016-12-13

Systemic mastocytosis are rare neoplasms characterized by accumulation of mast cells in at least one internal organ. The majority of systemic mastocytosis patients carry KIT D816V mutation, which activates constitutively the KIT receptor. Patient with advanced forms of systemic mastocytosis, such as aggressive systemic mastocytosis or mast cell leukemia, are poorly treated to date. Unfortunately, the lack of in vivo models reflecting KIT D816V+ advanced disease hampers pathophysiological studies and preclinical development of new therapies for such patients. Here, we describe a new in vivo model of KIT D816V+ advanced systemic mastocytosis developed by transplantation of the human ROSAKIT D816V-Gluc mast cell line in NOD-SCID IL-2R γ-/- mice, using Gaussia princeps luciferase as a reporter. Intravenous injection of ROSAKIT D816V-Gluc cells led, in 4 weeks, to engraftment in all injected primary recipient mice. Engrafted cells were found at high levels in bone marrow, and at lower levels in spleen, liver and peripheral blood. Disease progression was easily monitored by repeated quantification of Gaussia princeps luciferase activity in peripheral blood. This quantification evidenced a linear relationship between the number of cells injected and the neoplastic mast cell burden in mice. Interestingly, the secondary transplantation of ROSAKIT D816V-Gluc cells increased their engraftment capability. To conclude, this new in vivo model mimics at the best the features of human KIT D816V+ advanced systemic mastocytosis. In addition, it is a unique and convenient tool to study the kinetics of the disease and the potential in vivo activity of new drugs targeting neoplastic mast cells.

Neutrophil Recruitment by Tumor Necrosis Factor from Mast Cells in Immune Complex Peritonitis

NASA Astrophysics Data System (ADS)

Zhang, Yan; Ramos, Bernard F.; Jakschik, Barbara A.

1992-12-01

During generalized immune complex-induced inflammation of the peritoneal cavity, two peaks of tumor necrosis factor (TNF) were observed in the peritoneal exudate of normal mice. In mast cell-deficient mice, the first peak was undetected, and the second peak of TNF and neutrophil influx were significantly reduced. Antibody to TNF significantly inhibited neutrophil infiltration in normal but not in mast cell-deficient mice. Mast cell repletion of the latter normalized TNF, neutrophil mobilization, and the effect of the antibody to TNF. Thus, in vivo, mast cells produce the TNF that augments neutrophil emigration.

Mast Cells Can Enhance Resistance to Snake and Honeybee Venoms

NASA Astrophysics Data System (ADS)

Metz, Martin; Piliponsky, Adrian M.; Chen, Ching-Cheng; Lammel, Verena; Åbrink, Magnus; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

2006-07-01

Snake or honeybee envenomation can cause substantial morbidity and mortality, and it has been proposed that the activation of mast cells by snake or insect venoms can contribute to these effects. We show, in contrast, that mast cells can significantly reduce snake-venom-induced pathology in mice, at least in part by releasing carboxypeptidase A and possibly other proteases, which can degrade venom components. Mast cells also significantly reduced the morbidity and mortality induced by honeybee venom. These findings identify a new biological function for mast cells in enhancing resistance to the morbidity and mortality induced by animal venoms.

Urticaria pigmentosa

MedlinePlus

... occurs when there are too many inflammatory cells (mast cells) in the skin. Mast cells are immune system cells that help the body fight infections. Mast cells make and release histamine, which causes nearby tissues ...

Seed rain, soil seed bank, seed loss and regeneration of Castanopsis fargesii (Fagaceae) in a subtropical evergreen broad-leaved forest

USGS Publications Warehouse

Du, X.; Guo, Q.; Gao, X.; Ma, K.

2007-01-01

Understanding the seed rain and seed loss dynamics in the natural condition has important significance for revealing the natural regeneration mechanisms. We conducted a 3-year field observation on seed rain, seed loss and natural regeneration of Castanopsis fargesii Franch., a dominant tree species in evergreen broad-leaved forests in Dujiangyan, southwestern China. The results showed that: (1) there were marked differences in (mature) seed production between mast (733,700 seeds in 2001) and regular (51,200 and 195,600 seeds in 2002 and 2003, respectively) years for C. fargesii. (2) Most seeds were dispersed in leaf litter, humus and 0-2 cm depth soil in seed bank. (3) Frequency distributions of both DBH and height indicated that C. fargesii had a relatively stable population. (4) Seed rain, seed ground density, seed loss, and leaf fall were highly dynamic and certain quantity of seeds were preserved on the ground for a prolonged time due to predator satiation in both the mast and regular years so that the continuous presence of seed bank and seedling recruitments in situ became possible. Both longer time observations and manipulative experiments should be carried out to better understand the roles of seed dispersal and regeneration process in the ecosystem performance. ?? 2006 Elsevier B.V. All rights reserved.

Hericium erinaceus polysaccharide facilitates restoration of injured intestinal mucosal immunity in Muscovy duck reovirus-infected Muscovy ducklings.

PubMed

Wu, Yijian; Jiang, Huihui; Zhu, Erpeng; Li, Jian; Wang, Quanxi; Zhou, Wuduo; Qin, Tao; Wu, Xiaoping; Wu, Baocheng; Huang, Yifan

2018-02-01

To elucidate the effect of Hericium erinaceus polysaccharide (HEP) on the intestinal mucosal immunity in normal and Muscovy duck reovirus (MDRV)-infected Muscovy ducklings, 1-day-old healthy Muscovy ducklings were pretreated with 0.2g/L HEP and/or following by MDRV infection in this study, duodenal samples were respectively collected at 1, 3, 6, 10, 15 and 21day post-infection, tissue sections were prepared for observation of morphological structure and determination of intestinal parameters (villus height/crypt depth ratio, villus surface area) as well as counts of intraepithelial lymphocytes (IELs), goblet cells, mast cells. Additionally, dynamics of secretory immunoglobin A (sIgA), interferon-γ (IFN-γ) and interleukin-4 (IL-4) productions in intestinal mucosa were measured with radioimmunoassay. Results showed that HEP significantly improved intestinal morphological structure and related indexes, and significantly inhibited the reduction of intestinal mucosal IELs, goblet cells and mast cells caused by MDRV infection. Furthermore, HEP significantly increased the secretion of sIgA, IFN-γ and IL-4 to enhance intestinal mucosal immune functions. Our findings indicate that HEP treatment can effectively repair MDRV-caused injures of small intestinal mucosal immune barrier, and improve mucosal immune function in sick Muscovy ducklings, which will provide valuable help for further application of HEP in prevention and treatment of MDRV infection. Copyright © 2017. Published by Elsevier B.V.

3D display for enhanced tele-operation and other applications

NASA Astrophysics Data System (ADS)

Edmondson, Richard; Pezzaniti, J. Larry; Vaden, Justin; Hyatt, Brian; Morris, James; Chenault, David; Bodenhamer, Andrew; Pettijohn, Bradley; Tchon, Joe; Barnidge, Tracy; Kaufman, Seth; Kingston, David; Newell, Scott

2010-04-01

In this paper, we report on the use of a 3D vision field upgrade kit for TALON robot consisting of a replacement flat panel stereoscopic display, and multiple stereo camera systems. An assessment of the system's use for robotic driving, manipulation, and surveillance operations was conducted. A replacement display, replacement mast camera with zoom, auto-focus, and variable convergence, and a replacement gripper camera with fixed focus and zoom comprise the upgrade kit. The stereo mast camera allows for improved driving and situational awareness as well as scene survey. The stereo gripper camera allows for improved manipulation in typical TALON missions.

Mast cell proteases as pharmacological targets

PubMed Central

Caughey, George H.

2015-01-01

Mast cells are rich in proteases, which are the major proteins of intracellular granules and are released with histamine and heparin by activated cells. Most of these proteases are active in the granule as well outside of the mast cell when secreted, and can cleave targets near degranulating mast cells and in adjoining tissue compartments. Some proteases released from mast cells reach the bloodstream and may have far-reaching actions. In terms of relative amounts, the major mast cell proteases include the tryptases, chymases, cathepsin G, carboxypeptidase A3, dipeptidylpeptidase I/cathepsin C, and cathepsins L and S. Some mast cells also produce granzyme B, plasminogen activators, and matrix metalloproteinases. Tryptases and chymases are almost entirely mast cell-specific, whereas other proteases, such as cathepsins G, C, and L are expressed by a variety of inflammatory cells. Carboxypeptidase A3 expression is a property shared by basophils and mast cells. Other proteases, such as mastins, are largely basophil-specific, although human basophils are protease-deficient compared with their murine counterparts. The major classes of mast cell proteases have been targeted for development of therapeutic inhibitors. Also, a human β-tryptase has been proposed as a potential drug itself, to inactivate of snake venins. Diseases linked to mast cell proteases include allergic diseases, such as asthma, eczema, and anaphylaxis, but also include non-allergic diseases such inflammatory bowel disease, autoimmune arthritis, atherosclerosis, aortic aneurysms, hypertension, myocardial infarction, heart failure, pulmonary hypertension and scarring diseases of lungs and other organs. In some cases, studies performed in mouse models suggest protective or homeostatic roles for specific proteases (or groups of proteases) in infections by bacteria, worms and other parasites, and even in allergic inflammation. At the same time, a clearer picture has emerged of differences in the properties and patterns of expression of proteases expressed in human mast cell subsets, and in humans versus other mammals. These considerations are influencing prioritization of specific protease targets for therapeutic inhibition, as well as options of pre-clinical models, disease indications, and choice of topical versus systemic routes of inhibitor administration. PMID:25958181

Mast cell proteases as protective and inflammatory mediators.

PubMed

Caughey, George H

2011-01-01

Proteases are the most abundant class of proteins produced by mast cells. Many of these are stored in membrane-enclosed intracellular granules until liberated by degranulating stimuli, which include cross-linking of high affinity IgE receptor F(c)εRI by IgE bound to multivalent allergen. Understanding and separating the functions of the proteases is important because expression differs among mast cells in different tissue locations. Differences between laboratory animals and humans in protease expression also influence the degree of confidence with which results obtained in animal models of mast cell function can be extrapolated to humans. The inflammatory potential of mast cell proteases was the first aspect of their biology to be explored and has received the most attention, in part because some of them, notably tryptases and chymases, are biomarkers of local and systemic mast cell degranulation and anaphylaxis. Although some of the proteases indeed augment allergic inflammation and are potential targets for inhibition to treat asthma and related allergic disorders, they are protective and even anti-inflammatory in some settings. For example, mast cell tryptases may protect from serious bacterial lung infections and may limit the "rubor" component of inflammation caused by vasodilating neuropeptides in the skin. Chymases help to maintain intestinal barrier function and to expel parasitic worms and may support blood pressure during anaphylaxis by generating angiotensin II. In other life-or-death examples, carboxypeptidase A3 and other mast cell peptidases limit systemic toxicity of endogenous peptideslike endothelin and neurotensin during septic peritonitis and inactivate venom-associated peptides. On the other hand, mast cell peptidase-mediated destruction of protective cytokines, like IL-6, can enhance mortality from sepsis. Peptidases released from mast cells also influence nonmast cell proteases, such as by activating matrix metalloproteinase cascades, which are important in responses to infection and resolution of tissue injury. Overall, mast cell proteases have a variety of roles, inflammatory and anti-inflammatory, protective and deleterious, in keeping with the increasingly well-appreciated contributions of mast cells in allergy, tissue homeostasis and innate immunity.

Screening for hazardous drinking using the Michigan Alcohol Screening Test-Geriatric Version (MAST-G) in elderly persons with acute cerebrovascular accidents.

PubMed

Johnson-Greene, Doug; McCaul, Mary E; Roger, Patricia

2009-09-01

Effective and valid screening methods are needed to identify hazardous drinking in elderly persons with new onset acute medical illness. The goal of the current study was to examine the effectiveness of the Michigan Alcohol Screening Test-Geriatric Version (MAST-G) in identifying hazardous drinking among elderly patients with acute cerebrovascular accidents (CVA) and to compare the effectiveness of 2 shorter versions of the MAST-G with the full instrument. The study sample included 100 men and women who averaged 12 days posthemorrhagic or ischemic CVA admitted to a rehabilitation unit and who were at least 50 years of age and free of substance use other than alcohol. This cross-sectional validation study compared the 24-item full MAST-G, the 10-item Short MAST-G (SMAST-G), and a 2-item regression analysis derived Mini MAST-G (MMAST-G) to the reference standard of hazardous drinking during the past 3 months. Alcohol use was collected using the Timeline Followback (TLFB). Recent and lifetime alcohol-related consequences were collected using the Short Inventory of Problems (SIP). Nearly one-third (28%) of the study sample met the World Health Organization (WHO) criteria for hazardous drinking. Moderately strong associations were found for the MAST-G, SMAST-G, and MMAST-G with alcohol quantity and frequency and recent and lifetime alcohol consequences. All 3 MAST-G versions could differentiate hazardous from nonhazardous drinkers and had nearly identical area under the curve characteristics. Comparable sensitivity was found across the 3 MAST-G measures. The optimal screening threshold for hazardous drinking was 5 for the MAST-G, 2 for the SMAST-G, and 1 for the MMAST-G. The 10-item SMAST-G and 2-item MMAST-G are brief screening tests that show comparable effectiveness in detecting hazardous drinking in elderly patients with acute CVA compared with the full 24-item MAST-G. Implications for research and clinical practice are discussed.

Neuropeptides activate human mast cell degranulation and chemokine production

PubMed Central

Kulka, Marianna; Sheen, Cecilia H; Tancowny, Brian P; Grammer, Leslie C; Schleimer, Robert P

2008-01-01

During neuronal-induced inflammation, mast cells may respond to stimuli such as neuropeptides in an FcεRI-independent manner. In this study, we characterized human mast cell responses to substance P (SP), nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) and compared these responses to human mast cell responses to immunoglobulin E (IgE)/anti-IgE and compound 48/80. Primary cultured mast cells, generated from CD34+ progenitors in the presence of stem cell factor and interleukin-6 (IL-6), and human cultured mast cells (LAD2) were stimulated with these and other stimuli (gastrin, concanavalin A, radiocontrast media, and mannitol) and their degranulation and chemokine production was assessed. VIP and SP stimulated primary human mast cells and LAD cells to degranulate; gastrin, concanavalin A, radiocontrast media, mannitol, CGRP and NGF did not activate degranulation. While anti-IgE stimulation did not induce significant production of chemokines, stimulation with VIP, SP or compound 48/80 potently induced production of monocyte chemoattractant protein-1, inducible protein-10, monokine induced by interferon-γ (MIG), RANTES (regulated on activation, normal, T-cell expressed, and secreted) and IL-8. VIP, SP and compound 48/80 also activated release of tumour necrosis factor, IL-3 and granulocyte–macrophage colony-stimulating factor, but not IL-4, interferon-γ or eotaxin. Human mast cells expressed surface neurokinin 1 receptor (NK1R), NK2R, NK3R and VIP receptor type 2 (VPAC2) but not VPAC1 and activation of human mast cells by IgE/anti-IgE up-regulated expression of VPAC2, NK2R, and NK3R. These studies demonstrate the pattern of receptor expression and activation of mast cell by a host of G-protein coupled receptor ligands and suggest that SP and VIP activate a unique signalling pathway in human mast cells. These results are likely to have direct relevance to neuronally induced inflammatory diseases. PMID:17922833

IgE Immune Complexes Stimulate an Increase in Lung Mast Cell Progenitors in a Mouse Model of Allergic Airway Inflammation

PubMed Central

Dahlin, Joakim S.; Ivarsson, Martin A.; Heyman, Birgitta; Hallgren, Jenny

2011-01-01

Mast cell numbers and allergen specific IgE are increased in the lungs of patients with allergic asthma and this can be reproduced in mouse models. The increased number of mast cells is likely due to recruitment of mast cell progenitors that mature in situ. We hypothesized that formation of IgE immune complexes in the lungs of sensitized mice increase the migration of mast cell progenitors to this organ. To study this, a model of allergic airway inflammation where mice were immunized with ovalbumin (OVA) in alum twice followed by three daily intranasal challenges of either OVA coupled to trinitrophenyl (TNP) alone or as immune complexes with IgE-anti-TNP, was used. Mast cell progenitors were quantified by a limiting dilution assay. IgE immune complex challenge of sensitized mice elicited three times more mast cell progenitors per lung than challenge with the same dose of antigen alone. This dose of antigen challenge alone did not increase the levels of mast cell progenitors compared to unchallenged mice. IgE immune complex challenge of sensitized mice also enhanced the frequency of mast cell progenitors per 106 mononuclear cells by 2.1-fold. The enhancement of lung mast cell progenitors by IgE immune complex challenge was lost in FcRγ deficient mice but not in CD23 deficient mice. Our data show that IgE immune complex challenge enhances the number of mast cell progenitors in the lung through activation of an Fc receptor associated with the FcRγ chain. This most likely takes place via activation of FcεRI, although activation via FcγRIV or a combination of the two receptors cannot be excluded. IgE immune complex-mediated enhancement of lung MCp numbers is a new reason to target IgE in therapies against allergic asthma. PMID:21625525

Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans

PubMed Central

Asadi, Shahrzad; Sismanopoulos, Nikolaos; Butcher, Alan; Fu, Xueyan; Katsarou-Katsari, Alexandra; Antoniou, Christina; Theoharides, Theoharis C.

2012-01-01

Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance P (SP), and do not respond to conventional treatment. Inhibition of mast cell cytokine release could be effective therapy for such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only compound marketed as a mast cell “stabilizer”, is not particularly effective in blocking human mast cells. Instead, flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD2. Que and cromolyn also inhibit histamine, leukotrienes and PGD2 from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment. In summary, Que is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, especially in formulations that permit more sufficient oral absorption. PMID:22470478

Differential eosinophil and mast cell regulation: Mast cell viability and accumulation in inflammatory tissue are independent of proton-sensing receptor GPR65

PubMed Central

Zhu, Xiang; Mose, Eucabeth; Hogan, Simon P.

2014-01-01

Extracellular acidification has been observed in allergic inflammatory diseases. Recently, we demonstrated that the proton-sensing receptor G protein-coupled receptor 65 (GPR65) regulates eosinophil survival in an acidic environment in vitro and eosinophil accumulation in an allergic lung inflammation model. For mast cells, another inflammatory cell type critical for allergic responses, it remains unknown whether GPR65 is expressed and/or regulates mast cell viability. Thus, in the present study, we employed in vitro experiments and an intestinal anaphylaxis model in which both mastocytosis and eosinophilia can be observed, particularly in the gastrointestinal tract, to enable us to directly compare the effect of GPR65 expression on these two cell types. We identified GPR65 expression on mast cells; however, unlike eosinophil viability, mast cell viability in vitro is not affected by acidification or GPR65 expression. Mechanistically, we determined that mast cells do not respond to extracellular acidification with increased cAMP levels. Furthermore, in the intestinal anaphylaxis model, we observed a significant reduction of eosinophils (59.1 ± 9.2% decrease) in the jejunum of allergen-challenged GPR65-deficient mice compared with allergen-challenged wild-type mice, despite the degree of antigen sensitization and the expression levels of Th2 cytokines (Il4, Il13) and eosinophil chemokines (Ccl11, Ccl24) in the jejunum being comparable. In contrast, the accumulation of mast cells in allergen-challenged mice was not affected by GPR65 deficiency. In conclusion, our study demonstrates differential regulation of eosinophils and mast cells in inflammatory tissue, with mast cell viability and accumulation being independent of GPR65. PMID:24742990

Non-receptor tyrosine kinases ITK and BTK negatively regulate mast cell pro-inflammatory responses to lipopolysaccharide

PubMed Central

Huang, Weishan; Morales, J. Luis; Gozivoda, Victor P.; August, Avery

2015-01-01

Background Mast cells are indispensible for LPS-induced septic hypothermia, in which TNF-α plays an essential role to initiate septic responses. ITK and BTK regulate mast cell responses to allergen, but their roles in mast cell responses in LPS-induced sepsis are unclear. Objectives We sought to investigate the roles of ITK and BTK in mast cell responses during LPS-induced septic inflammation. Methods Mice (genetically modified or BMMC-reconstituted Sash) were given LPS to induce septic hypothermia, in the presence or absence of indicated inhibitors. Flow cytometry was used to determine LPS-induced cell influx and TNF-α production in peritoneal cells. Microarray was used for genome-wide gene expression analysis on BMMCs. Quantitative PCR and multiplex were used to determine transcribed and secreted pro-inflammatory cytokines. Microscopy and western blotting were used to determine activation of signal transduction pathways. Results The absence of ITK and BTK leads to exacerbation of LPS-induced septic hypothermia and neutrophil influx. Itk−/−Btk−/− mast cells exhibit hyperactive preformed and LPS-induced TNF-α production, and lead to more severe LPS-induced septic hypothermia when reconstituted into mast cell deficient Sash mice. LPS-induced NF-κB, Akt and p38 activation is enhanced in Itk−/−Btk−/− mast cells, and blockage of PI3K, Akt or p38 downstream MNK1 activation significantly suppresses TNF-α hyper-production and attenuates septic hypothermia. Conclusions ITK and BTK regulate thermal homeostasis during septic response through mast cell function in mice. They share regulatory function downstream of TLR4/LPS in mast cells, through regulating the activation of canonical NF-κB, PI3K/Akt and p38 signaling pathways. PMID:26581914

Evaluation of myeloid cells (tumor-associated tissue eosinophils and mast cells) infiltration in different grades of oral squamous cell carcinoma.

PubMed

Debta, Priyanka; Debta, Fakir Mohan; Chaudhary, Minal; Bussari, Smita

2016-01-01

The multifunctional involvement and infiltration of myeloid cells (tumor-associated tissue eosinophils [TATE] and mast cells) can provide a unique opportunity to define relevant effectors functions that may represent novel, therapeutic options for modulation of tumor onset/growth. Our study aimed to evaluate infiltration of myeloid cells (TATE and Mast cells) infiltration in different grades (WHO grading) of oral squamous cell carcinoma (OSCC). Total 30 cases of OSCC were selected for this study. Hematoxylin and eosin stain and toluidine blue special stain, to evaluate TATE and the mast cells infiltration, were used. Three-year follow-up of OSCC cases was done. Among 30 cases, 63.33% cases of OSCC showed TATE-positive and 36.66% cases showed TATE-negative. Regarding mast cells infiltration, 66.66% OSCC cases showed mast cells positive and 33.33% cases did not show significant mast cells infiltration. We found significant association of TATE and mast cells infiltration in OSCC cases. These myeloid cells infiltration significantly associated with age of patients but did not show any significant association with gender, site, and habit of cases. When we compared these cells infiltration with clinical stages and different histological grades of tumor, we found their infiltration is decreasing, from Stages 1 to Stage 3 of tumor and from well to poorly differentiated carcinoma. We have also found the less infiltration of these myeloid in recurrence cases of OSCC. As the infiltration of TATE and mast cells are correlated, along with evaluation of TATE, we should also evaluate the presence of mast cells infiltration in OSCC. The assessment of myeloid cells could become, in the future, useful for therapeutic approaches in this subset of the patient.

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

PubMed

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

2017-02-01

Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

Silver Nanoparticle-Directed Mast Cell Degranulation Is Mediated through Calcium and PI3K Signaling Independent of the High Affinity IgE Receptor

PubMed Central

Alsaleh, Nasser B.; Persaud, Indushekhar; Brown, Jared M.

2016-01-01

Engineered nanomaterial (ENM)-mediated toxicity often involves triggering immune responses. Mast cells can regulate both innate and adaptive immune responses and are key effectors in allergic diseases and inflammation. Silver nanoparticles (AgNPs) are one of the most prevalent nanomaterials used in consumer products due to their antimicrobial properties. We have previously shown that AgNPs induce mast cell degranulation that was dependent on nanoparticle physicochemical properties. Furthermore, we identified a role for scavenger receptor B1 (SR-B1) in AgNP-mediated mast cell degranulation. However, it is completely unknown how SR-B1 mediates mast cell degranulation and the intracellular signaling pathways involved. In the current study, we hypothesized that SR-B1 interaction with AgNPs directs mast cell degranulation through activation of signal transduction pathways that culminate in an increase in intracellular calcium signal leading to mast cell degranulation. For these studies, we utilized bone marrow-derived mast cells (BMMC) isolated from C57Bl/6 mice and RBL-2H3 cells (rat basophilic leukemia cell line). Our data support our hypothesis and show that AgNP-directed mast cell degranulation involves activation of PI3K, PLCγ and an increase in intracellular calcium levels. Moreover, we found that influx of extracellular calcium is required for the cells to degranulate in response to AgNP exposure and is mediated at least partially via the CRAC channels. Taken together, our results provide new insights into AgNP-induced mast cell activation that are key for designing novel ENMs that are devoid of immune system activation. PMID:27907088

Quantification and localization of mast cells in periapical lesions.

PubMed

Mahita, V N; Manjunatha, B S; Shah, R; Astekar, M; Purohit, S; Kovvuru, S

2015-01-01

Periapical lesions occur in response to chronic irritation in periapical tissue, generally resulting from an infected root canal. Specific etiological agents of induction, participating cell population and growth factors associated with maintenance and resolution of periapical lesions are incompletely understood. Among the cells found in periapical lesions, mast cells have been implicated in the inflammatory mechanism. Quantifications and the possible role played by mast cells in the periapical granuloma and radicular cyst. Hence, this study is to emphasize the presence (localization) and quantification of mast cells in periapical granuloma and radicular cyst. A total of 30 cases and out of which 15 of periapical granuloma and 15 radicular cyst, each along with the case details from the previously diagnosed cases in the department of oral pathology were selected for the study. The gender distribution showed male 8 (53.3%) and females 7 (46.7%) in periapical granuloma cases and male 10 (66.7%) and females 5 (33.3%) in radicular cyst cases. The statistical analysis used was unpaired t-test. Mean mast cell count in periapical granuloma subepithelial and deeper connective tissue, was 12.40 (0.99%) and 7.13 (0.83%), respectively. The mean mast cell counts in subepithelial and deeper connective tissue of radicular cyst were 17.64 (1.59%) and 12.06 (1.33%) respectively, which was statistically significant. No statistical significant difference was noted among males and females. Mast cells were more in number in radicular cyst. Based on the concept that mast cells play a critical role in the induction of inflammation, it is logical to use therapeutic agents to alter mast cell function and secretion, to thwart inflammation at its earliest phases. These findings may suggest the possible role of mast cells in the pathogenesis of periapical lesions.

Somatostatin inhibits intestinal mucosal mast cell degranulation in normal conditions and during mast cell hyperplasia.

PubMed

Saavedra, Y; Vergara, P

2003-03-28

Several studies demonstrate that intestinal mucosal mast cells (IMMC) are modulated by nervous reflexes as well as by intraluminal content. We recently demonstrated that peptones, such as ovalbumin hydrolysate (OVH), induce the release of rat mast cell protease II (RMCP II), indicating IMMC degranulation. The response is due to complex neuroendocrine reflexes. Somatostatin (SS) and its analogues have been used as potential treatments for inflammation in other body systems with contradictory results. The aim of this study was to evaluate if somatostatin could contribute to the reduction of intestinal mucosal mast cell degranulation. Anesthetized rats were prepared for duodenal perfusion and mast cell activation was measured by analysis of RMCP II concentration in the duodenal perfusate. Somatostatin significantly decreased RMCP II concentration in both nonstimulated conditions and after ovalbumin hydrolysate perfusion. However, when somatostatin was given previously to OVH, the peptone still induced a slight increase of RMCP II. Similar effects were observed in animals previously treated with capsaicin. These protocols were repeated in animals infected with Trichinella spiralis, which induces mucosal mast cell hyperplasia. In these cases, somatostatin blocked the effect of OVH, thus, preventing an increase in RMCP II concentration. Fresh frozen tissue sections from the duodenum were processed in an attempt to demonstrate the presence of SS receptors in mast cells using immunofluorescence and Fluo-peptide labeling techniques. Confocal images from duodenum specimens demonstrate the existence of SS receptors in positive cells for RMCP II. Taken together, these results indicate that somatostatin diminishes mast cell activity and in consequence could prevent the intestinal responses to mast cell hyperplasia. Copyright 2002 Elsevier Science B.V.

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

Yuan, Meichun; Department of Physiology, Hubei University of Medicine, Shiyan; Li, Jianjie

Mast cells play a key role in the pathogenesis of asthma and are a promising target for therapeutic intervention in asthma. This study investigated the effects of polydatin (PD), a resveratrol glucoside, on mast cell degranulation upon cross-linking of the high-affinity IgE receptors (FcεRI), as well as the anti-allergic activity of PD in vivo. Herein, we demonstrated that PD treatment for 30 min suppressed FcεRI-mediated mast cell degranulation in a dose-dependent manner. Concomitantly, PD significantly decreased FcεRI-mediated Ca{sup 2+} increase in mast cells. The suppressive effects of PD on FcεRI-mediated Ca{sup 2+} increase were largely inhibited by using LaCl{sub 3}more » to block the Ca{sup 2+} release-activated Ca{sup 2+} channels (CRACs). Furthermore, PD significantly inhibited Ca{sup 2+} entry through CRACs evoked by thapsigargin (TG). Knocking down protein expression of Orai1, the pore-forming subunit of CRACs, significantly decreased PD suppression of FcεRI-induced intracellular Ca{sup 2+} influx and mast cell degranulation. In a mouse model of mast cell-dependent passive cutaneous anaphylaxis (PCA), in vivo PD administration suppressed mast cell degranulation and inhibited anaphylaxis. Taken together, our data indicate that PD stabilizes mast cells by suppressing FcεRI-induced Ca{sup 2+} mobilization mainly through inhibiting Ca{sup 2+} entry via CRACs, thus exerting a protective effect against PCA. -- Highlights: ► Polydatin can prevent the pathogenesis of passive cutaneous anaphylaxis in mice. ► Polydatin stabilizes mast cells by decreasing FcεRI-mediated degranulation. ► Polydatin suppresses Ca{sup 2+} entry through CRAC channels in mast cells.« less

INFORMATION RETRIEVAL EXPERIMENT. FINAL REPORT.

ERIC Educational Resources Information Center

SELYE, HANS

THIS REPORT IS A BRIEF REVIEW OF RESULTS OF AN EXPERIMENT TO DETERMINE THE INFORMATION RETRIEVAL EFFICIENCY OF A MANUAL SPECIALIZED INFORMATION SYSTEM BASED ON 700,000 DOCUMENTS IN THE FIELDS OF ENDOCRINOLOGY, STRESS, MAST CELLS, AND ANAPHYLACTOID REACTIONS. THE SYSTEM RECEIVES 30,000 PUBLICATIONS ANNUALLY. DETAILED INFORMATION IS REPRESENTED BY…

Use of robotics for nondestructive inspection of steel highway bridges and structures : final report.

DOT National Transportation Integrated Search

2005-01-01

This report presents the results of a project to finalize and apply a crawling robotic system for the remote visual inspection of high-mast light poles. The first part of the project focused on finalizing the prototype crawler robot hardware and cont...

Excellent outcome of allogeneic hematopoietic SCT with reduced-intensity conditioning for the treatment of chronic active EBV infection.

PubMed

Kawa, K; Sawada, A; Sato, M; Okamura, T; Sakata, N; Kondo, O; Kimoto, T; Yamada, K; Tokimasa, S; Yasui, M; Inoue, M

2011-01-01

Since we reported the first successful case of allogeneic hematopoietic SCT (allo-HSCT), we have performed allo-HSCT for 29 patients with chronic active EBV infection (CAEBV), using either myeloablative conditioning (MAC) allo-HSCT (MAST) or reduced-intensity conditioning (RIC) allo-HSCT (RIST). In this retrospective analysis we compared the outcomes after MAST and RIST to identify the optimal conditioning for patients with CAEBV. Of 29 patients, 11 underwent allo-HSCT with MAC, consisting of TBI (12 Gy), etoposide (900 mg/m²) and CY (120 mg/kg) or melphalan (210 mg/m²), and the remaining 18 patients received allo-HSCT after RIC, consisting of fludarabine (∼ 180 mg/m²) and melphalan (140 mg/m²) or CY (120 mg/kg), with/without antithymocyte globulin and low-dose irradiation. Donor sources were 8 related BM, 2 related peripheral blood, 5 CD34 selected cells from HLA-haploidentical donors, 8 unrelated BM and 8 unrelated cord blood. The 3-year-EFS rate was 54.5 ± 15.0% for MAST group and 85.0 ± 8.0% for RIST group, and the 3-year OS rate was 54.5 ± 15.0% for MAST group and 95.0 ± 4.9% for RIST group (P = 0.016). Allo-HSCT after RIC seems to be a promising approach for the treatment of CAEBV.

Alterations in MAST suit pressure with changes in ambient temperature.

PubMed

Sanders, A B; Meislin, H W; Daub, E

1983-01-01

A study was undertaken to test the hypothesis that change in ambient air temperature has an effect on MAST suit pressure according to the ideal gas law. Two different MAST suits were tested on Resusci-Annie dummies. The MAST suits were applied in a cold room at 4.4 degrees C and warmed to 44 degrees C. Positive linear correlations were found in nine trials, but the two suits differed in their rate of increase in pressure. Three trials using humans were conducted showing increased pressure with temperature but at a lesser rate than with dummies. A correlation of 0.5 to 1.0 mm Hg increase in MAST suit pressure for each 1.0 degrees C increase in ambient temperature was found. Implications are discussed for the use of the MAST suit in environmental conditions where the temperature changes.

The role of colonic mast cells and myenteric plexitis in patients with diverticular disease.

PubMed

Bassotti, Gabrio; Villanacci, Vincenzo; Nascimbeni, Riccardo; Antonelli, Elisabetta; Cadei, Moris; Manenti, Stefania; Lorenzi, Luisa; Titi, Amin; Salerni, Bruno

2013-02-01

Gut mast cells represent an important cell population involved in intestinal homeostasis and inflammatory processes. However, their possible role has not to date been investigated in colonic diverticular disease. This study aims to evaluate colonic mast cells in patients undergoing surgery for diverticular disease. Surgical resection samples from 27 patients undergoing surgery for diverticular disease (12 emergency procedures for severe disease and 15 elective procedures) were evaluated. The number of mast cells was assessed in the various layers by means of a specific antibody (tryptase) and compared with those evaluated in ten controls. In patients with mast cells degranulation, double immunohistochemistry, also assessing nerve fibres, was carried out. In addition, the presence of myenteric plexitis was sought. Compared with controls, the number of mast cells in diverticular patients was significantly increased, both as an overall figure and in the various layers of the large bowel. In patients in whom mast cells degranulation was present, these were always closed to nerve fibres. No differences were found between the two subgroups of patients with respect to the number and distribution of mast cells; however, all patients undergoing emergency surgery (but none of those undergoing elective procedures) had myenteric plexitis, represented by lymphocytic infiltration in 67 % and eosinophilic infiltration in 33 % of cases. Patients with diverticular disease display an increase of mast cells in the large bowel. The presence of myenteric plexitis in those with complicated, severe disease, suggest that this could represent a histopathologic marker of more aggressive disease.

Proliferation of protease-enriched mast cells in sarcoptic skin lesions of raccoon dogs.

PubMed

Noviana, D; W Harjanti, D; Otsuka, Y; Horii, Y

2004-07-01

Skin sites, tongue, lung, liver, jejunum and rectum from two raccoon dogs with Sarcoptes scabiei infestation and five normal (control) raccoon dogs were examined in terms of the distribution, proteoglycan properties and protease activity of mast cells. Infestation with S. scabiei caused a significant increase in the number of dermal mast cells. While the number of mast cells (average +/- standard deviation) in specimens of skin from the dorsum, dorsal neck, dorsal hind foot and dorsal fore foot was 40.0 +/- 19.8/mm2 in control animals, it was 236.1 +/- 58.9/mm2 in the skin of mange-infested animals. Histochemical analysis revealed the glycosaminoglycan, heparin, within the mast cells of all organs examined in both control and affected animals. Enzyme-histochemical detection of serine proteases demonstrated an increase in mast-cell-specific protease activity (i.e., chymase and tryptase) in the skin of infested animals. The percentage of mast cells demonstrating chymase activity was 53.0 +/- 27.4% in control animals and 73.8 +/- 19.4% in mite-infested animals. The corresponding results for tryptase activity were 53.5 +/- 25.2% and 89.4 +/- 9.8%. Increases in mast cell chymase or tryptase activity, or both, were also observed within other organs of the infected animals, but the total number of mast cells found at such sites (with the exception of liver and ventrolateral pinna) did not differ from those of control animals. Copyright 2004 Elsevier Ltd.

Mast Cells Regulate Epidermal Barrier Function and the Development of Allergic Skin Inflammation.

PubMed

Sehra, Sarita; Serezani, Ana P M; Ocaña, Jesus A; Travers, Jeffrey B; Kaplan, Mark H

2016-07-01

Atopic dermatitis is a chronic inflammatory skin disease characterized by infiltration of eosinophils, T helper cells, and mast cells. The role of mast cells in atopic dermatitis is not completely understood. To define the effects of mast cells on skin biology, we observed that mast cells regulate the homeostatic expression of epidermal differentiation complex and other skin genes. Decreased epidermal differentiation complex gene expression in mice that genetically lack mast cells (Kit(W-sh/W-sh) mice) is associated with increased uptake of protein antigens painted on the skin by dendritic cells (DCs) compared with similarly treated wild-type mice, suggesting a protective role for mast cells in exposure to nominal environmental allergens. To test this further, we crossed Kit(W-sh/W-sh) mice with signal transducer and activator of transcription 6 (i.e., Stat6) VT transgenic mice that develop spontaneous atopic dermatitis-like disease that is dependent on T helper cell 2 cytokines and is associated with high serum concentrations of IgE. We observed that Stat6VT × Kit(W-sh/W-sh) mice developed more frequent and more severe allergic skin inflammation than Stat6VT transgenic mice that had mast cells. Together, these studies suggest that mast cells regulate epidermal barrier function and have a potential protective role in the development of atopic dermatitis-like disease. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Hydrocortisone and dexamethasone dose-dependently stabilize mast cells derived from rat peritoneum.

PubMed

Mori, Tomohiro; Abe, Nozomu; Saito, Kazutomo; Toyama, Hiroaki; Endo, Yasuhiro; Ejima, Yutaka; Yamauchi, Masanori; Goto, Mariko; Mushiake, Hajime; Kazama, Itsuro

2016-12-01

Besides their anti-inflammatory properties, corticosteroid drugs exert anti-allergic effects. Exocytosis of mast cells is electrophysiologically detected as the increase in the whole-cell membrane capacitance (Cm). Therefore, the lack of such increase after exposure to the drugs suggests their mast cell-stabilizing effects. We examined the effects of 1, 10, 100 and 200μM hydrocortisone or dexamethasone on the degranulation from rat peritoneal mast cells. Employing the whole-cell patch-clamp recording technique, we also tested their effects on the Cm during exocytosis. At relatively lower concentrations (1, 10μM), both hydrocortisone and dexamethasone did not significantly affect the degranulation from mast cells and the increase in the Cm induced by GTP-γ-S. Nevertheless, at higher doses (100, 200μM), these drugs inhibited the degranulation from mast cells and markedly suppressed the GTP-γ-S-induced increase in the Cm. Our results provided electrophysiological evidence for the first time that corticosteroid drugs, such as hydrocortisone and dexamethasone, inhibited the exocytotic process of mast cells in a dose-dependent manner. The mast cell-stabilizing effects of these drugs may be attributable to their "non-genomic" action, by which they exert rapid anti-allergic effects. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Direct effects of IL-4 on mast cells drive their intestinal expansion and increase susceptibility to anaphylaxis in a murine model of food allergy

PubMed Central

Burton, Oliver T; Darling, Alanna R; Zhou, Joseph S; Noval-Rivas, Magali; Jones, Tatiana G; Gurish, Michael F; Chatila, Talal A; Oettgen, Hans C

2012-01-01

IL-4 plays critical roles in allergic disorders, including food hypersensitivity. The direct effects of the cytokine on the survival and function of mast cells, the key effectors of food anaphylaxis, have not been established. In this study we demonstrate that IL-4 induces a marked intestinal mastocytosis in mice. This phenotype is reproduced in animals expressing Il4rαF709, an activating variant of the IL-4 receptor α (IL-4Rα)-chain. Il4rαF709 mice exhibit enhanced anaphylactic reactions but unaltered physiologic responses to vasoactive mediators. IL-4 induces Bcl-2 and Bcl-XL, and enhances survival and stimulates proliferation in cultured bone marrow mast cells (BMMC). These effects are STAT6-dependent and are amplified in Il4rαF709 BMMC. In competitive bone marrow chimeras, Il4rαF709 mast cells display a substantial competitive advantage over wild-type mast cells which, in turn, prevail over IL-4Rα−/− mast cells in populating the intestine, establishing a cell intrinsic effect of IL-4 in intestinal mast cell homeostasis. Our results demonstrate that IL-4-signaling is a key determinant of mast cell expansion in food allergy. PMID:23149659

Increased mast cell density in haemorrhoid venous blood vessels suggests a role in pathogenesis.

PubMed

Taweevisit, M; Wisadeopas, N; Phumsuk, U; Thorner, P S

2008-12-01

Haemorrhoids are an abnormal, tortuous dilatation of the arteriovenous plexus of the anus. Although increased resting anorectal pressure is deemed to be a major initiating factor, a thorough understanding of the pathogenesis is still lacking. Mast cells, through release of granules, can affect local vessels with respect to changes in calibre, changes in permeability and thrombosis. Thus, mast cells could play a role in haemorrhoid pathophysiology, although this has not been previously investigated. 48 cases of haemorrhoids were retrospectively collected at King Chulalongkorn Memorial Hospital, with normal anorectal tissue from surgically-removed colorectal cancer serving as controls. Mast cells were identified by toluidine blue staining and quantitated around venous vessels. Mast cells around haemorrhoidal vessels were significantly more numerous than in normal specimens (p-value is less than 0.001). Similar values were found for haemorrhoids showing chronic changes and those in a more acute stage. These findings support the hypothesis that mast cells may play a role in the pathophysiology of haemorrhoids. Mast cells appear to participate equally in the early and later stages of these lesions. Mast cells are known to affect local vascular conditions through release of their chemical mediators and cytokines, and may influence haemorrhoid symptomatology and progression at this level.

Subthreshold IKK activation modulates the effector functions of primary mast cells and allows specific targeting of transformed mast cells

PubMed Central

Drube, Sebastian; Beyer, Mandy; Rothe, Mandy; Rabenhorst, Anja; Göpfert, Christiane; Meininger, Isabel; Diamanti, Michaela A.; Stegner, David; Häfner, Norman; Böttcher, Martin; Reinecke, Kirstin; Herdegen, Thomas; Greten, Florian R.; Nieswandt, Bernhard; Hartmann, Karin; Krämer, Oliver H.; Kamradt, Thomas

2015-01-01

Mast cell differentiation and proliferation depends on IL-3. IL-3 induces the activation of MAP-kinases and STATs and consequently induces proliferation and survival. Dysregulation of IL-3 signaling pathways also contribute to inflammation and tumorigenesis. We show here that IL-3 induces a SFK- and Ca2+-dependent activation of the inhibitor of κB kinases 2 (IKK2) which results in mast cell proliferation and survival but does not induce IκBα-degradation and NFκB activation. Therefore we propose the term “subthreshold IKK activation”. This subthreshold IKK activation also primes mast cells for enhanced responsiveness to IL-33R signaling. Consequently, co-stimulation with IL-3 and IL-33 increases IKK activation and massively enhances cytokine production induced by IL-33. We further reveal that in neoplastic mast cells expressing constitutively active Ras, subthreshold IKK activation is associated with uncontrolled proliferation. Consequently, pharmacological IKK inhibition reduces tumor growth selectively by inducing apoptosis in vivo. Together, subthreshold IKK activation is crucial to mediate the full IL-33-induced effector functions in primary mast cells and to mediate uncontrolled proliferation of neoplastic mast cells. Thus, IKK2 is a new molecularly defined target structure. PMID:25749030

The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury

PubMed Central

Fang, Hui; Zhang, Yang; Li, Ning; Wang, Gang; Liu, Zhi

2018-01-01

Bullous pemphigoid (BP) is an autoimmune and inflammatory skin disease associated with subepidermal blistering and autoantibodies directed against the hemidesmosomal components BP180 and BP230. Animal models of BP were developed by passively transferring anti-BP180 IgG into mice, which recapitulates the key features of human BP. By using these in vivo model systems, key cellular and molecular events leading to the BP disease phenotype are identified, including binding of pathogenic IgG to its target, complement activation of the classical pathway, mast cell degranulation, and infiltration and activation of neutrophils. Proteinases released by infiltrating neutrophils cleave BP180 and other hemidesmosome-associated proteins, causing DEJ separation. Mast cells and mast cell-derived mediators including inflammatory cytokines and proteases are increased in lesional skin and blister fluids of BP. BP animal model evidence also implicates mast cells in the pathogenesis of BP. However, recent studies questioned the pathogenic role of mast cells in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and epidermolysis bullosa acquisita. This review highlights the current knowledge on BP pathophysiology with a focus on a potential role for mast cells in BP and mast cell-related critical issues needing to be addressed in the future. PMID:29545809

Mast cell-neural interactions contribute to pain and itch.

PubMed

Gupta, Kalpna; Harvima, Ilkka T

2018-03-01

Mast cells are best recognized for their role in allergy and anaphylaxis, but increasing evidence supports their role in neurogenic inflammation leading to pain and itch. Mast cells act as a "power house" by releasing algogenic and pruritogenic mediators, which initiate a reciprocal communication with specific nociceptors on sensory nerve fibers. Consequently, nerve fibers release inflammatory and vasoactive neuropeptides, which in turn activate mast cells in a feedback mechanism, thus promoting a vicious cycle of mast cell and nociceptor activation leading to neurogenic inflammation and pain/pruritus. Mechanisms underlying mast cell differentiation, activation, and intercellular interactions with inflammatory, vascular, and neural systems are deeply influenced by their microenvironment, imparting enormous heterogeneity and complexity in understanding their contribution to pain and pruritus. Neurogenic inflammation is central to both pain and pruritus, but specific mediators released by mast cells to promote this process may vary depending upon their location, stimuli, underlying pathology, gender, and species. Therefore, in this review, we present the contribution of mast cells in pathological conditions, including distressing pruritus exacerbated by psychologic stress and experienced by the majority of patients with psoriasis and atopic dermatitis and in different pain syndromes due to mastocytosis, sickle cell disease, and cancer. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pavlovian Conditioning of Rat Mucosal Mast Cells to Secrete Rat Mast Cell Protease II

NASA Astrophysics Data System (ADS)

MacQueen, Glenda; Marshall, Jean; Perdue, Mary; Siegel, Shepard; Bienenstock, John

1989-01-01

Antigen (egg albumin) injections, which stimulate mucosal mast cells to secrete mediators, were paired with an audiovisual cue. After reexposure to the audiovisual cue, a mediator (rat mast cell protease II) was measured with a sensitive and specific assay. Animals reexposed to only the audiovisual cue released a quantity of protease not significantly different from animals reexposed to both the cue and the antigen; these groups released significantly more protease than animals that had received the cue and antigen in a noncontingent manner. The results support a role for the central nervous system as a functional effector of mast cell function in the allergic state.

Curiosity on Tilt Table with Mast Up

NASA Image and Video Library

2011-03-25

The Mast Camera Mastcam on NASA Mars rover Curiosity has two rectangular eyes near the top of the rover remote sensing mast. This image shows Curiosity on a tilt table NASA Jet Propulsion Laboratory, Pasadena, California.

Relation between mast cells concentration and serotonin expression in chagasic megacolon development.

PubMed

Freitas, M A R; Segatto, N; Tischler, N; de Oliveira, E C; Brehmer, A; da Silveira, A B M

2017-03-01

Chagas' disease is still reaching about 10 million people in the world. In South America, one of the most severe forms of this disease is the megacolon, characterized by severe constipation, dilated sigmoid colon and rectum and severe malnutrition. Previous data suggested that mast cells and serotonin (5-hydroxytryptamine [5-HT]) expression could be involved in intestinal homeostasis control, avoiding the chagasic megacolon development. The aim at this study was to characterize the presence of mast cells and expression of serotonin in chagasic patients with and without megacolon and evaluate the relation between mast cells, serotonin and megacolon development. Our results demonstrated that patients without megacolon feature a large amount of serotonin and few mast cells, while patients with megacolon feature low serotonin expression and a lot of mast cells. We believe that serotonin may be involved in the inflammatory process control, triggered by mast cells, and the presence of this substance in large quantities of the intestine could represent a mechanism of megacolon prevention. © 2017 John Wiley & Sons Ltd.

Mast fruiting of large ectomycorrhizal African rain forest trees: importance of dry season intensity, and the resource-limitation hypothesis.

PubMed

Newbery, David M; Chuyong, George B; Zimmermann, Lukas

2006-01-01

Mast fruiting is a distinctive reproductive trait in trees. This rain forest study, at a nutrient-poor site with a seasonal climate in tropical Africa, provides new insights into the causes of this mode of phenological patterning. At Korup, Cameroon, 150 trees of the large, ectomycorrhizal caesalp, Microberlinia bisulcata, were recorded almost monthly for leafing, flowering and fruiting during 1995-2000. The series was extended to 1988-2004 with less detailed data. Individual transitions in phenology were analysed. Masting occurred when the dry season before fruiting was drier, and the one before that was wetter, than average. Intervals between events were usually 2 or 3 yr. Masting was associated with early leaf exchange, followed by mass flowering, and was highly synchronous in the population. Trees at higher elevation showed more fruiting. Output declined between 1995 and 2000. Mast fruiting in M. bisulcata appears to be driven by climate variation and is regulated by internal tree processes. The resource-limitation hypothesis was supported. An 'alternative bearing' system seems to underlie masting. That ectomycorrhizal habit facilitates masting in trees is strongly implied.

Thrombomodulin inhibits the activation of eosinophils and mast cells.

PubMed

Roeen, Ziaurahman; Toda, Masaaki; D'Alessandro-Gabazza, Corina N; Onishi, Masahiro; Kobayashi, Tetsu; Yasuma, Taro; Urawa, Masahito; Taguchi, Osamu; Gabazza, Esteban C

2015-01-01

Eosinophils and mast cells play critical roles in the pathogenesis of bronchial asthma. Activation of both cells leads to the release of pro-inflammatory mediators in the airway of asthmatic patients. Recently, we have shown that inhaled thrombomodulin inhibits allergic bronchial asthma in a mouse model. In the present study, we hypothesize that thrombomodulin can inhibit the activation of eosinophils and mast cells. The effect of thrombomodulin on the activation and release of inflammatory mediators from eosinophils and mast cells was evaluated. Thrombomodulin inhibited the eotaxin-induced chemotaxis, upregulation of CD11b and degranulation of eosinophils. Treatment with thrombomodulin also significantly suppressed the degranulation and synthesis of inflammatory cytokines and chemokines in eosinophils and mast cells. Mice treated with a low-dose of inhaled thrombomodulin have decreased number of eosinophils and activated mast cells and Th2 cytokines in the lungs compared to untreated mice. The results of this study suggest that thrombomodulin may modulate allergic responses by inhibiting the activation of both eosinophils and mast cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Possible Involvement of Human Mast Cells in the Establishment of Pregnancy via Killer Cell Ig-Like Receptor 2DL4.

PubMed

Ueshima, Chiyuki; Kataoka, Tatsuki R; Hirata, Masahiro; Sugimoto, Akihiko; Iemura, Yoshiki; Minamiguchi, Sachiko; Nomura, Takashi; Haga, Hironori

2018-06-01

The involvement of mast cells in the establishment of pregnancy is unclear. Herein, we found that human mast cells are present in the decidual tissues of parous women and expressed a human-specific protein killer cell Ig-like receptor (KIR) 2DL4, a receptor for human leukocyte antigen G expressed on human trophoblasts. In contrast, decreased numbers of decidual mast cells and reduced KIR2DL4 expression were observed in these cells of infertile women who had undergone long-term corticosteroid treatment. Co-culture of the human mast cell line, LAD2, and human trophoblast cell line, HTR-8/SVneo, accelerated the migration and tube formation of HTR-8/SVneo cells in a KIR2DL4-dependent manner. These observations suggest the possible involvement of human mast cells in the establishment of pregnancy via KIR2DL4 and that long-term corticosteroid treatment may cause infertility by influencing the phenotypes of decidual mast cells. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Utility of Fite-Faraco stain for both mast cell count and bacillary index in skin biopsies of leprosy patients.

PubMed

Chatura, K R; Sangeetha, S

2012-01-01

To assess the utility of a single stain for both mast cell count and bacillary index (BI), 50 skin-biopsie patients were stained with Fite-Faraco (FF) stain, viewed under oil immersion and BI calculated using the Ridley's logarithmic scale, and mast cells counted as the number of cells per mm2. Mean mast cell count per mm2 at the tuberculoid pole was lowest in TT 7.9 and highest in BT 14.23. At the lepromatous end, it was highest in BL 9.21, while in LL it was 8.23. Highest counts were seen in the borderline types overall. The correlation coefficient between histopathological diagnosis and BI is 0.822 which is a positive correlation to a significant degree. The correlation coefficient between histopathological diagnosis and mast cell count was found to be -0.17, which is a negative correlation but not to a significant degree. FF stain was utilised to visualise both bacilli for estimation of BI and mast cells for mast cell count, a seldom attempted feature in literature.

Extendable mast used in one shot soil penetrometer

NASA Technical Reports Server (NTRS)

Hotz, G. M.; Howard, G. A.

1966-01-01

Penetrometer to test soil characteristics has a piercing head with soil instrumentation equipment attached to an expandable mast actuated by compressed air. The penetrometer gives continuous measurements as the mast pushes the piercing head through the soil.

Multiple co morbid conditions in patient with Mast Cell Activation Syndrome

DTIC Science & Technology

2017-10-26

conditions in patient \\\\·ith Mast Cell Activation Syndron1e Sb. GRANT NUMBER Sc. PROGRAM.ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER Maj Sofia...13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple co-n1orhid conditions in patient \\Vith Mast Cell Activation Syndrotne Sofia M. Szari.MD. and James...Defense. !NTR()D{JCT!ON: Mast cell activation disorders {MCAD) have been associated \\Vilh Connective Tissue Disorders (CTD) and orthostatic

Porcine mast cells infected with H1N1 influenza virus release histamine and inflammatory cytokines and chemokines.

PubMed

Lee, In Hong; Kim, Hyun Soo; Seo, Sang Heui

2017-04-01

Mast cells reside in many tissues, including the lungs, and might play a role in enhancing influenza virus infections in animals. In this study, we cultured porcine mast cells from porcine bone marrow cells with IL-3 and stem cell factor to study the infectivity and activation of the 2009 pandemic H1N1 influenza virus of swine origin. Porcine mast cells were infected with H1N1 influenza virus, without the subsequent production of infectious viruses but were activated, as indicated by the release of histamines. Inflammatory cytokine- and chemokine-encoding genes, including IL-1α, IL-6, CXCL9, CXCL10, and CXCL11, were upregulated in the infected porcine mast cells. Our results suggest that mast cells could be involved in enhancing influenza-virus-mediated disease in infected animals.

Update on Mastocytosis (Part 2): Categories, Prognosis, and Treatment.

PubMed

Azaña, J M; Torrelo, A; Matito, A

2016-01-01

Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in different organs. The organ most often affected is the skin. The World Health Organization classifies cutaneous mastocytosis into mastocytoma, maculopapular cutaneous mastocytosis, and diffuse mastocytosis. The systemic variants in this classification are as follows: indolent systemic mastocytosis (SM), aggressive SM, SM with an associated clonal hematological non-mast cell lineage disease, mast cell leukemia, mast cell sarcoma, and extracutaneous mastocytoma. The two latest systemic variants are rare. Although the course of disease is unpredictable in children, lesions generally resolve by early adulthood. In adults, however, the disease tends to persist. The goal of treatment should be to control clinical manifestations caused by the release of mast cell mediators and, in more aggressive forms of the disease, to reduce mast cell burden. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Detection of mast cell secretion by using surface enhanced Raman scattering

NASA Astrophysics Data System (ADS)

Li, Juan; Li, Ren; Zheng, Liqin; Wang, Yuhua; Xie, Shusen; Lin, Juqiang

2016-10-01

Acupuncture can cause a remarkable increase in degranulation of the mast cells, which has attracted the interest of researchers since the 1980s. Surface-enhanced Raman scattering (SERS) could obtain biochemical information with high sensitivity and specificity. In this study, SERS was used to detect the degree of degranulation of mast cells according to different incubate time. Mast cells was incubated with culture medium for 0 h, 12 h and 24 h, then centrifuge the culture medium, decant the supernatant, and discard the mast cell. SERS was performed to obtain the biochemical fingerprinting signatures of the centrifuged medium. The spectra data are then analyzed by spectral peaks attribution and the principal component analysis (PCA). The measured Raman spectra of the two groups were separated well by PCA. It indicated that mast cells had secreted some substances into cultured medium though degranulation did not happen.

Mast Cells: Pivotal Players in Cardiovascular Diseases

PubMed Central

Bot, Ilze; van Berkel, Theo J.C; Biessen, Erik A.L

2008-01-01

The clinical outcome of cardiovascular diseases as myocardial infarction and stroke are generally caused by rupture of an atherosclerotic plaque. However, the actual cause of a plaque to rupture is not yet established. Interestingly, pathology studies have shown an increased presence of the mast cell, an important inflammatory effector cell in allergy and host defense, in (peri)vascular tissue during plaque progression, which may point towards a causal role for mast cells. Very recent data in mouse models show that mast cells and derived mediators indeed can profoundly impact plaque progression, plaque stability and acute cardiovascular syndromes such as vascular aneurysm or myocardial infarction. In this review, we discuss recent evidence on the role of mast cells in the progression of cardiovascular disorders and give insight in the therapeutic potential of modulation of mast cell function in these processes to improve the resilience of a plaque to rupture. PMID:19936193

The impact of mast cells on cardiovascular diseases.

PubMed

Kritikou, Eva; Kuiper, Johan; Kovanen, Petri T; Bot, Ilze

2016-05-05

Mast cells comprise an innate immune cell population, which accumulates in tissues proximal to the outside environment and, upon activation, augments the progression of immunological reactions through the release and diffusion of either pre-formed or newly generated mediators. The released products of mast cells include histamine, proteases, as well as a variety of cytokines, chemokines and growth factors, which act on the surrounding microenvironment thereby shaping the immune responses triggered in various diseased states. Mast cells have also been detected in the arterial wall and are implicated in the onset and progression of numerous cardiovascular diseases. Notably, modulation of distinct mast cell actions using genetic and pharmacological approaches highlights the crucial role of this cell type in cardiovascular syndromes. The acquired evidence renders mast cells and their mediators as potential prognostic markers and therapeutic targets in a broad spectrum of pathophysiological conditions related to cardiovascular diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Mast cells and mastocytosis

PubMed Central

2008-01-01

Mast cells have been recognized for well over 100 years. With time, human mast cells have been documented to originate from CD34+ cells, and have been implicated in host responses in both innate and acquired immunity. In clinical immunology, they are recognized for their central role in IgE-mediated degranulation and allergic inflammation by virtue of their expression of the high-affinity receptor for IgE and release of potent proinflammatory mediators. In hematology, the clinical disease of mastocytosis is characterized by a pathologic increase of mast cells in tissues, often associated with mutations in KIT, the receptor for stem cell factor. More recently, and with increased understanding of how human mast cells are activated through receptors including the high-affinity receptor for IgE and KIT, specific tyrosine kinase inhibitors have been identified with the potential to interrupt signaling pathways and thus limit the proliferation of mast cells as well as their activation through immunoglobulin receptors. PMID:18684881

Basic science for the clinician 53: mast cells.

PubMed

Sigal, Leonard H

2011-10-01

Mast cells stand at the interface between the innate immune system and the acquired (adaptive) immune response, serving as sentinels detecting invaders and directing a concerted and coordinated response. Mast cells reside immediately under body surfaces and within lymph nodes, near blood vessels and nerves, perfectly situated to for early detection and defense. They secrete a wide array of prostanoids, cytokines, chemokines, and other proteins mediators and modifiers of a variety of immune and inflammatory functions and bear surface markers suggesting broad functions, including as antigen-presenting cells. Although usually not given their due in medical school lectures, there is great likelihood that mast cells will be implicated in the pathogenesis of rheumatoid arthritis, scleroderma, multiple sclerosis, and perhaps cancer. Thus, better insights into mast cell functions and mast cell-derived effector molecules should command our attention as we move forward in better understanding disease immunopathogenesis and directed intelligent therapeutics development.

Influence of mass moment of inertia on normal modes of preloaded solar array mast

NASA Technical Reports Server (NTRS)

Armand, Sasan C.; Lin, Paul

1992-01-01

Earth-orbiting spacecraft often contain solar arrays or antennas supported by a preloaded mast. Because of weight and cost considerations, the structures supporting the spacecraft appendages are extremely light and flexible; therefore, it is vital to investigate the influence of all physical and structural parameters that may influence the dynamic behavior of the overall structure. The study primarily focuses on the mast for the space station solar arrays, but the formulations and the techniques developed in this study apply to any large and flexible mast in zero gravity. Furthermore, to determine the influence on the circular frequencies, the mass moment of inertia of the mast was incorporated into the governing equation of motion for bending. A finite element technique (MSC/NASTRAN) was used to verify the formulation. Results indicate that when the mast is relatively flexible and long, the mass moment inertia influences the circular frequencies.

Bone marrow-derived cultured mast cells and peritoneal mast cells as targets of a growth activity secreted by BALB/3T3 fibroblasts

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

Jozaki, K.; Kuriu, A.; Hirota, S.

1991-03-01

When fibroblast cell lines were cultured in contact with bone marrow-derived cultured mast cells (CMC), both NIH/3T3 and BALB/3T3 cell lines supported the proliferation of CMC. In contrast, when contact between fibroblasts and CMC was prohibited by Biopore membranes or soft agar, only BALB/3T3 fibroblasts supported CMC proliferation, suggesting that BALB/3T3 but not NIH/3T3 cells secreted a significant amount of a mast cell growth activity. Moreover, the BALB/3T3-derived growth activity induced the incorporation of (3H)thymidine by CMC and the clonal growth of peritoneal mast cells in methylcellulose. The mast cell growth activity appeared to be different from interleukin 3 (IL-3)more » and interleukin 4 (IL-4), because mRNAs for these interleukins were not detectable in BALB/3T3 fibroblasts. Although mast cells are genetically deficient in tissues of W/Wv mice, CMC did develop when bone marrow cells of W/Wv mice were cultured with pokeweed mitogen-stimulated spleen cell-conditioned medium. Because BALB/3T3 fibroblast-conditioned medium (BALB-FCM) did not induce the incorporation of (3H)thymidine by W/Wv CMC, the growth activity in BALB-FCM appeared to be a ligand for the receptor encoded by the W (c-kit) locus. Because CMC and peritoneal mast cells are obtained as homogeneous suspensions rather easily, these cells may be potentially useful as targets for the fibroblast-derived mast cell growth activity.« less

The Mastocytosis Society survey on mast cell disorders: patient experiences and perceptions.

PubMed

Jennings, Susan; Russell, Nancy; Jennings, Blair; Slee, Valerie; Sterling, Lisa; Castells, Mariana; Valent, Peter; Akin, Cem

2014-01-01

Mast cell diseases include mastocytosis and mast cell activation syndromes, some of which have been shown to involve clonal defects in mast cells that result in abnormal cellular proliferation or activation. Numerous clinical studies of mastocytosis have been published, but no population-based comprehensive surveys of patients in the United States have been identified. Few mast cell disease specialty centers exist in the United States, and awareness of these mast cell disorders is limited among nonspecialists. Accordingly, information concerning the experiences of the overall estimated population of these patients has been lacking. To identify the experiences and perceptions of patients with mastocytosis, mast cell activation syndromes, and related disorders, The Mastocytosis Society (TMS), a US based patient advocacy, research, and education organization, conducted a survey of its members and other people known or suspected to be part of this patient population. A Web-based survey was publicized through clinics that treat these patients and through TMS's newsletter, Web site, and online blogs. Both online and paper copies of the questionnaire were provided, together with required statements of consent. The first results are presented for 420 patients. These results include demographics, diagnoses, symptoms, allergies, provoking factors of mast cell symptoms, and disease impact. Patients with mastocytosis and mast cell activation syndromes have provided clinical specialists, collaborators, and other patients with information to enable them to explore and deepen their understanding of the experiences and perceptions of people coping with these disorders. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Vaccine adjuvants: Tailor-made mast-cell granules

NASA Astrophysics Data System (ADS)

Gunzer, Matthias

2012-03-01

Mast cells induce protective immune responses through secretion of stimulatory granules. Microparticles modelled after mast-cell granules are now shown to replicate and enhance the functions of their natural counterparts and to direct the character of the resulting immunity.

MAST - A mass spectrometer telescope for studies of the isotopic composition of solar, anomalous, and galactic cosmic ray nuclei

NASA Technical Reports Server (NTRS)

Cook, Walter R.; Cummings, Alan C.; Cummings, Jay R.; Garrard, Thomas L.; Kecman, Branislav; Mewaldt, Richard A.; Selesnick, Richard S.; Stone, Edward C.; Von Rosenvinge, T. T.

1993-01-01

The Mass Spectrometer Telescope (MAST) on SAMPEX is designed to provide high resolution measurements of the isotopic composition of energetic nuclei from He to Ni (Z = 2 to 28) over the energy range from about 10 to several hundred MeV/nuc. During large solar flares MAST will measure the isotopic abundances of solar energetic particles to determine directly the composition of the solar corona, while during solar quiet times MAST will study the isotopic composition of galactic cosmic rays. In addition, MAST will measure the isotopic composition of both interplanetary and trapped fluxes of anomalous cosmic rays, believed to be a sample of the nearby interstellar medium.

KSC-2009-1002

NASA Image and Video Library

2009-01-02

CAPE CANAVERAL, Fla. – On Launch Pad 39B at NASA's Kennedy Space Center in Florida, equipment surrounds the service structures for the construction of towers in the new lightning protection system for the Constellation Program and Ares/Orion launches. In the foreground is part of the giant crane used to place segments on the towers. Each of the three new lightning towers will be 500 feet tall with an additional 100-foot fiberglass mast (seen on the ground) atop supporting a wire catenary system. This improved lightning protection system allows for the taller height of the Ares I rocket compared to the space shuttle. Pad 39B will be the site of the first Ares vehicle launch, including the Ares I-X test flight that is targeted for July 2009. Photo credit: NASA/Troy Cryder

Solar Array Mast Imagery Discussion for ISIW

NASA Technical Reports Server (NTRS)

Kilgo, Gary

2017-01-01

SAW Mast inspection background: In 2012, NASA's Flight Safety Office requested the Micro Meteoroid and Orbital Debris (MMOD) office determine the probability of damage to the Solar Array Wing (SAW) mast based on the exposure over the life time of the ISS program. As part of the risk mitigation of the potential MMOD strikes. ISS Program office along with the Image Science and Analysis Group (ISAG) began developing methods for imaging the structural components of the Mast.

Hydrogen inhalation ameliorated mast cell-mediated brain injury after intracerebral hemorrhage in mice.

PubMed

Manaenko, Anatol; Lekic, Tim; Ma, Qingyi; Zhang, John H; Tang, Jiping

2013-05-01

Hydrogen inhalation was neuroprotective in several brain injury models. Its mechanisms are believed to be related to antioxidative stress. We investigated the potential neurovascular protective effect of hydrogen inhalation especially effect on mast cell activation in a mouse model of intracerebral hemorrhage. Controlled in vivo laboratory study. Animal research laboratory. One hundred seventy-one 8-week-old male CD-1 mice were used. Collagenase-induced intracerebral hemorrhage model in 8-week-old male CD-1 mice was used. Hydrogen was administrated via spontaneous inhalation. The blood-brain barrier permeability and neurologic deficits were investigated at 24 and 72 hours after intracerebral hemorrhage. Mast cell activation was evaluated by Western blot and immuno-staining. The effects of hydrogen inhalation on mast cell activation were confirmed in an autologous blood injection model intracerebral hemorrhage. At 24 and 72 hours post intracerebral hemorrhage, animals showed blood-brain barrier disruption, brain edema, and neurologic deficits, accompanied with phosphorylation of Lyn kinase and release of tryptase, indicating mast cell activation. Hydrogen treatment diminished phosphorylation of Lyn kinase and release of tryptase, decreased accumulation and degranulation of mast cells, attenuated blood-brain barrier disruption, and improved neurobehavioral function. Activation of mast cells following intracerebral hemorrhage contributed to increase of blood-brain barrier permeability and brain edema. Hydrogen inhalation preserved blood-brain barrier disruption by prevention of mast cell activation after intracerebral hemorrhage.

Hydrogen inhalation ameliorated mast cell mediated brain injury after ICH in mice

PubMed Central

Manaenko, Anatol; Lekic, Tim; Ma, Qingyi; Zhang, John H.; Tang, Jiping

2012-01-01

OBJECTIVE Hydrogen inhalation was neuroprotective in several brain injury models. Its mechanisms are believed to be related to anti-oxidative stress. We investigated the potential neurovascular protective effect of hydrogen inhalation especially effect on mast cell activation in a mouse model of intracerebral hemorrhage (ICH). DESIGN Controlled in vivo laboratory study. SETTING Animal research laboratory SUBJECTS 171, 8 weeks old male CD-1 mice were used. INTERVENTIONS Collagenase-induced ICH model in 8 weeks old, male, CD-1 mice was used. Hydrogen was administrated via spontaneous inhalation. The blood-brain barrier (BBB) permeability and neurological deficits were investigated at 24 and 72 hours after ICH. Mast cell activation was evaluated by Western blot and immuno-staining. The effects of hydrogen inhalation on mast cell activation were confirmed in an autologous blood injection model ICH. MEASURMENT AND MAIN RESULTS At 24 and 72 hours post-ICH, animals showed BBB disruption, brain edema, neurological deficits, accompanied with phosphorylation of Lyn kinase and release of tryptase, indicating mast cell activation. Hydrogen treatment diminished phosphorylation of Lyn kinase and release of tryptase, decreased accumulation and degranulation of mast cells, attenuated BBB disruption and improved neurobehavioral function. CONCLUSION Activation of mast cells following ICH contributed to increase of BBB permeability and brain edema. Hydrogen inhalation preserved BBB disruption by prevention of mast cell activation after ICH. PMID:23388512

Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel.

PubMed

Yu, Y; Daly, D M; Adam, I J; Kitsanta, P; Hill, C J; Wild, J; Shorthouse, A; Grundy, D; Jiang, W

2016-10-01

Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro-immune association in the human bowel. Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age-related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell-nerve micro-anatomical association were investigated by histological and immune staining. Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo-sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P-immunoreactive (SP-IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP-IR nerves. Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell-nerve association suggest a compensatory mechanism for sensory neurodegeneration. © 2016 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion.

PubMed

Mackins, Christina J; Kano, Seiichiro; Seyedi, Nahid; Schäfer, Ulrich; Reid, Alicia C; Machida, Takuji; Silver, Randi B; Levi, Roberto

2006-04-01

Having identified renin in cardiac mast cells, we assessed whether its release leads to cardiac dysfunction. In Langendorff-perfused guinea pig hearts, mast cell degranulation with compound 48/80 released Ang I-forming activity. This activity was blocked by the selective renin inhibitor BILA2157, indicating that renin was responsible for Ang I formation. Local generation of cardiac Ang II from mast cell-derived renin also elicited norepinephrine release from isolated sympathetic nerve terminals. This action was mediated by Ang II-type 1 (AT1) receptors. In 2 models of ischemia/reperfusion using Langendorff-perfused guinea pig and mouse hearts, a significant coronary spillover of renin and norepinephrine was observed. In both models, this was accompanied by ventricular fibrillation. Mast cell stabilization with cromolyn or lodoxamide markedly reduced active renin overflow and attenuated both norepinephrine release and arrhythmias. Similar cardioprotection was observed in guinea pig hearts treated with BILA2157 or the AT1 receptor antagonist EXP3174. Renin overflow and arrhythmias in ischemia/reperfusion were much less prominent in hearts of mast cell-deficient mice than in control hearts. Thus, mast cell-derived renin is pivotal for activating a cardiac renin-angiotensin system leading to excessive norepinephrine release in ischemia/reperfusion. Mast cell-derived renin may be a useful therapeutic target for hyperadrenergic dysfunctions, such as arrhythmias, sudden cardiac death, myocardial ischemia, and congestive heart failure.

Mast cells in the human lung at high altitude

NASA Astrophysics Data System (ADS)

Heath, Donald

1992-12-01

Mast cell densities in the lung were measured in five native highlanders of La Paz (3600 m) and in one lowlander dying from high-altitude pulmonary oedema (HAPO) at 3440 m. Two of the highlanders were mestizos with normal pulmonary arteries and the others were Aymara Indians with muscular remodelling of their pulmonary vasculature. The aim of the investigation was to determine if accumulation of mast cells in the lung at high altitude (HA) is related to alveolar hypoxia alone, to a combination of hypoxia and muscularization of the pulmonary arterial tree, or to oedema of the lung. The lungs of four lowlanders were used as normoxic controls. The results showed that the mast cell density of the two Mestizos was in the normal range of lowlanders (0.6-8.8 cells/mm2). In the Aymara Indians the mast cell counts were raised (25.6-26.0 cells/mm2). In the lowlander dying from HAPO the mast cell count was greatly raised to 70.1 cells/mm2 lung tissue. The results show that in native highlanders an accumulation of mast cells in the lung is not related to hypoxia alone but to a combination of hypoxia and muscular remodelling of the pulmonary arteries. However, the most potent cause of increased mast cell density in the lung at high altitude appears to be high-altitude pulmonary oedema.

Fire timing in relation to masting: an important determinant of post-fire recruitment success for the obligate-seeding arid zone soft spinifex (Triodia pungens).

PubMed

Wright, Boyd R; Fensham, Roderick J

2018-01-25

Plant species with fire-triggered germination are common in many fire-prone ecosystems. For such plants, fire timing in relation to the timing of reproduction may strongly influence post-fire population regeneration if: (a) flowering occurs infrequently (e.g. plants are mast seeders); and (b) seed survival rates are low and input from the current year's flowering therefore contributes a large proportion of the viable dormant seedbank. The role of fire timing in relation to masting as a driver of post-fire recruitment has rarely been examined directly, so this study tested the hypothesis that fires shortly after masting trigger increased recruitment of the obligate-seeding arid zone spinifex, Triodia pungens R. Br., an iteroparous masting grass with smoke-cued germination. Phenological monitoring of T. pungens was conducted over 5 years, while a longitudinal seedbank study assessed the influence of seeding events on soil-stored seedbank dynamics. Concurrently, a fire experiment with randomized blocking was undertaken to test whether T. pungens hummocks burnt shortly after masting have greater post-fire recruitment than hummocks burnt when there has not been recent input of seeds. Triodia pungens flowered in all years, though most flowerings were characterized by high rates of flower abortion. A mast flowering with high seed set in 2012 triggered approx. 200-fold increases in seedbank densities, and seedbank densities remained elevated for 24 months after this event. The fire experiment showed significantly higher recruitment around hummocks burnt 6 months after the 2012 mast event than around hummocks that were burnt but prevented from masting by having inflorescences clipped. Fires shortly after masting trigger mass recruitment in T. pungens because such fires synchronize an appropriate germination cue (smoke) with periods when seedbank densities are elevated. Interactions between natural fire regimes, seedbank dynamics and fire management prescriptions must be considered carefully when managing fire-sensitive masting plants such as T. pungens. © The Author(s) 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

GATEWAY Report Brief: SSL Evaluation: Philadelphia International Airport Apron Lighting

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

None, None

Summary of report that documents a trial installation of LED apron lighting that replaced the existing high-pressure sodium luminaires at Philadelphia International Airport. Such high-mast applications remain challenging for LED technology, and the lessons learned from this project may help facility managers and LED product manufacturers better meet those challenges.

Synthesis of Gallic Acid Analogs as Histamine and Pro-Inflammatory Cytokine Inhibitors for Treatment of Mast Cell-Mediated Allergic Inflammation.

PubMed

Fei, Xiang; Je, In-Gyu; Shin, Tae-Yong; Kim, Sang-Hyun; Seo, Seung-Yong

2017-05-29

Gallic acid (3,4,5-trihydroxybenzoic acid), is a natural product found in various foods and herbs that are well known as powerful antioxidants. Our previous report demonstrated that it inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. In this report, various amide analogs of gallic acid have been synthesized by introducing different amines through carbodiimide-mediated amide coupling and Pd/C-catalyzed hydrogenation. These compounds showed a modest to high inhibitory effect on histamine release and pro-inflammatory cytokine expression. Among them, the amide bearing ( S )-phenylglycine methyl ester 3d was found to be more active than natural gallic acid. Further optimization yielded several ( S )- and ( R )-phenylglycine analogs that inhibited histamine release in vitro. Our findings suggest that some gallamides could be used as a treatment for allergic inflammatory diseases.

Arm and Mast of NASA Mars Rover Curiosity

NASA Image and Video Library

2011-04-06

The arm and the remote sensing mast of the Mars rover Curiosity each carry science instruments and other tools for NASA Mars Science Laboratory mission. This image shows the arm on the left and the mast just right of center.

Quantification and Localization of Mast Cells in Periapical Lesions

PubMed Central

Mahita, VN; Manjunatha, BS; Shah, R; Astekar, M; Purohit, S; Kovvuru, S

2015-01-01

Background: Periapical lesions occur in response to chronic irritation in periapical tissue, generally resulting from an infected root canal. Specific etiological agents of induction, participating cell population and growth factors associated with maintenance and resolution of periapical lesions are incompletely understood. Among the cells found in periapical lesions, mast cells have been implicated in the inflammatory mechanism. Aim: Quantifications and the possible role played by mast cells in the periapical granuloma and radicular cyst. Hence, this study is to emphasize the presence (localization) and quantification of mast cells in periapical granuloma and radicular cyst. Materials and Methods: A total of 30 cases and out of which 15 of periapical granuloma and 15 radicular cyst, each along with the case details from the previously diagnosed cases in the department of oral pathology were selected for the study. The gender distribution showed male 8 (53.3%) and females 7 (46.7%) in periapical granuloma cases and male 10 (66.7%) and females 5 (33.3%) in radicular cyst cases. The statistical analysis used was unpaired t-test. Results: Mean mast cell count in periapical granuloma subepithelial and deeper connective tissue, was 12.40 (0.99%) and 7.13 (0.83%), respectively. The mean mast cell counts in subepithelial and deeper connective tissue of radicular cyst were 17.64 (1.59%) and 12.06 (1.33%) respectively, which was statistically significant. No statistical significant difference was noted among males and females. Conclusion: Mast cells were more in number in radicular cyst. Based on the concept that mast cells play a critical role in the induction of inflammation, it is logical to use therapeutic agents to alter mast cell function and secretion, to thwart inflammation at its earliest phases. These findings may suggest the possible role of mast cells in the pathogenesis of periapical lesions. PMID:25861530

The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm

PubMed Central

Jawhar, Mohamad; Schwaab, Juliana; Meggendorfer, Manja; Naumann, Nicole; Horny, Hans-Peter; Sotlar, Karl; Haferlach, Torsten; Schmitt, Karla; Fabarius, Alice; Valent, Peter; Hofmann, Wolf-Karsten; Cross, Nicholas C.P.; Metzgeroth, Georgia; Reiter, Andreas

2017-01-01

Mast cell leukemia is a rare variant of advanced systemic mastocytosis characterized by at least 20% of mast cells in a bone marrow smear. We evaluated clinical and molecular characteristics of 28 patients with (n=20, 71%) or without an associated hematologic neoplasm. De novo mast cell leukemia was diagnosed in 16 of 28 (57%) patients and secondary mast cell leukemia evolving from other advanced systemic mastocytosis subtypes in 12 of 28 (43%) patients, of which 7 patients progressed while on cytoreductive treatment. Median bone marrow mast cell infiltration was 65% and median serum tryptase was 520 μg/L. C-findings were identified in 26 of 28 (93%) patients. Mutations in KIT (D816V, n=19; D816H/Y, n=5; F522C, n=1) were detected in 25 of 28 (89%) patients and prognostically relevant additional mutations in SRSF2, ASXL1 or RUNX1 (S/A/Rpos) in 13 of 25 (52%) patients. Overall response rate in 18 treatment-naïve patients was 5 of 12 (42%) on midostaurin and 1 of 6 (17%) on cladribine, and after switch 1 of 4 (25%) on midostaurin and 0 of 3 on cladribine, respectively. S/A/Rpos adversely affected response to treatment and progression to secondary mast cell leukemia (n=6) or acute myeloid leukemia (n=3) while on treatment (P<0.05). The median overall survival from mast cell leukemia diagnosis was 17 months as compared to 44 months in a control group of 124 patients with advanced systemic mastocytosis but without mast cell leukemia (P=0.03). In multivariate analyses, S/A/Rpos remained the only independent poor prognostic variable predicting overall survival (P=0.007). In conclusion, the molecular signature should be determined in all patients with mast cell leukemia because of its significant clinical and prognostic relevance. PMID:28255023

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans-Infection of CD4+ T Cells.

PubMed

Jiang, Ai-Ping; Jiang, Jin-Feng; Wei, Ji-Fu; Guo, Ming-Gao; Qin, Yan; Guo, Qian-Qian; Ma, Li; Liu, Bao-Chi; Wang, Xiaolei; Veazey, Ronald S; Ding, Yong-Bing; Wang, Jian-Hua

2015-12-30

The gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4β7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4(+) T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viral trans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection. In this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1 trans-infection of CD4(+) T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Winds at the Phoenix Landing Site

NASA Astrophysics Data System (ADS)

Holstein-Rathlou, C.; Gunnlaugsson, H. P.; Taylor, P.; Lange, C.; Moores, J.; Lemmon, M.

2008-12-01

Local wind speeds and directions have been measured at the Phoenix landing site using the Telltale wind indicator. The Telltale is mounted on top of the meteorological mast at roughly 2 meters height above the surface. The Telltale is a mechanical anemometer consisting of a lightweight cylinder suspended by Kevlar fibers that are deflected under the action of wind. Images taken with the Surface Stereo Imager (SSI) of the Telltale deflection allows the wind speed and direction to be quantified. Winds aloft have been estimated using image series (10 images ~ 50 s apart) taken of the Zenith (Zenith Movies). In contrast enhanced images cloud like features are seen to move through the image field and give indication of directions and angular speed. Wind speeds depend on the height of where these features originate while directions are unambiguously determined. The wind data shows dominant wind directions and diurnal variations, likely caused by slope winds. Recent night time measurements show frost formation on the Telltale mirror. The results will be discussed in terms of global and slope wind modeling and the current calibration of the data is discussed. It will also be illustrated how wind data can aid in interpreting temperature fluctuations seen on the lander.

Small clusters of fast-growing trees enhance forest structure on restored bottomland sites

USGS Publications Warehouse

Twedt, D.J.

2006-01-01

Despite the diversity of trees in bottomland forests, restoration on bottomland sites is often initiated by planting only a few species of slow-growing, hard mast?producing trees. Although successful at establishing trees, these young forests are slow to develop vertical structure, which is a key predictor of forest bird colonization. Furthermore, when natural seed sources are few, restored sites may be depauperate in woody species. To increase richness of woody species, maximum tree height, and total stem density, I supplemented traditional plantings on each of 40 bottomland restoration sites by planting 96 Eastern cottonwood (Populus deltoides) and American sycamore (Platanus occidentalis) in eight clusters of 12 trees. First year survival of cottonwood stem cuttings (25%) and sycamore seedlings (47%) was poor, but survival increased when afforded protection from competition with weeds. After five growing seasons, 165 of these 320 supplemental tree clusters had at least one surviving tree. Vegetation surrounding surviving clusters of supplemental trees harbored a greater number of woody species, increased stem density, and greater maximum tree height than was found on paired restoration sites without supplemental trees. These increases were primarily accounted for by the supplemental trees.

Mast cells in rheumatoid arthritis: friends or foes?

PubMed

Rivellese, Felice; Nerviani, Alessandra; Rossi, Francesca Wanda; Marone, Gianni; Matucci-Cerinic, Marco; de Paulis, Amato; Pitzalis, Costantino

2017-06-01

Mast cells are tissue-resident cells of the innate immunity, implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). They are present in synovia and their activation has been linked to the potentiation of inflammation in the course of RA. However, recent investigations questioned the role of mast cells in arthritis. In particular, animal models generated conflicting results, so that many of their pro-inflammatory, i.e. pro-arthritogenic functions, even though supported by robust experimental evidence, have been labelled as redundant. At the same time, a growing body of evidence suggests that mast cells can act as tunable immunomodulatory cells. These characteristics, not yet fully understood in the context of RA, could partially explain the inconsistent results obtained with experimental models, which do not account for the pro- and anti-inflammatory functions exerted in more chronic heterogeneous conditions such as RA. Here we present an overview of the current knowledge on mast cell involvement in RA, including the intriguing hypothesis of mast cells acting as subtle immunomodulatory cells and the emerging concept of synovial mast cells as potential biomarkers for patient stratification. Copyright © 2017 Elsevier B.V. All rights reserved.

Different Patterns of Mast Cells Distinguish Diffuse from Encapsulated Neurofibromas in Patients with Neurofibromatosis 1

PubMed Central

Tucker, Tracy; Riccardi, Vincent M.; Sutcliffe, Margaret; Vielkind, Juergen; Wechsler, Janine; Wolkenstein, Pierre; Friedman, Jan M.

2011-01-01

Multiple neurofibromas are cardinal features of neurofibromatosis 1 (NF1). Several different types of NF1-associated neurofibromas occur, each distinct in terms of pathological details, clinical presentation, and natural history. Mast cells are present in most neurofibromas and have been shown to be critical to the origin and progression of neurofibromas in both human NF1 and relevant mouse models. In this investigation, the authors determined whether mast cell involvement is the same for all types of NF1-associated neurofibromas. They examined the density and distribution of mast cells within 49 NF1-associated neurofibromas classified histopathologically as diffuse or encapsulated on the basis of the presence or absence of the perineurium or its constituent cells. They made two observations: (1) Diffuse neurofibromas had significantly higher densities of mast cells than did encapsulated neurofibromas, and (2) mast cells were evenly distributed throughout diffuse neurofibromas but were primarily restricted to the periphery of encapsulated neurofibromas. The differences in mast cell density and distribution differentiate the two basic types of NF1-associated neurofibromas, suggesting that the pathogenesis of diffuse and encapsulated neurofibromas may be significantly different. PMID:21525187

[Sex differences in neuromodulation of mucosal mast cells in the rat jejunum].

PubMed

Gottwald, T; Becker, H D; Stead, R H

1997-01-01

The effect of electrical stimulation of both cervical vagal nerves on mucosal mast cells in the jejunum was investigated in an in vivo animal model with rats of both sexes. Males showed a significant increase of mast cell densities after electrical stimulation (1.0 mA, 5 Hz, 5 ms, 12 min) in the lamina propria. Simultaneously, we observed a significant increase of tissue histamine levels (ANOVA: P < 0.05), whereas serum levels remained unchanged. However, even though females had significantly higher levels throughout compared to males (ANOVA: P < 0.05), they did not show any significant reaction to electrical stimulation. These in vivo data support morphological and in vitro data from other investigators, who hypothesized a functional interaction between mucosal mast cells and nerves. However, degranulation seems to be a poor in situ indicator for mast-cell stimulation, as mast-cell densities increased in males, while the percentage of degranulated cells remained the same in all groups (about 40%). Instead, electrical stimulation of the vagal nerve seems to trigger histamine synthesis, or simply stabilization of mast cells. Interestingly, this phenomenon seems to be sex-dependent, suggesting a regulatory role for sex hormones in this scenario.

Terreic acid, a quinone epoxide inhibitor of Bruton’s tyrosine kinase

PubMed Central

Kawakami, Yuko; Hartman, Stephen E.; Kinoshita, Eiji; Suzuki, Hidefumi; Kitaura, Jiro; Yao, Libo; Inagaki, Naoki; Franco, Alessandra; Hata, Daisuke; Maeda-Yamamoto, Mari; Fukamachi, Hiromi; Nagai, Hiroichi; Kawakami, Toshiaki

1999-01-01

Bruton’s tyrosine kinase (Btk) plays pivotal roles in mast cell activation as well as in B cell development. Btk mutations lead to severe impairments in proinflammatory cytokine production induced by cross-linking of high-affinity IgE receptor on mast cells. By using an in vitro assay to measure the activity that blocks the interaction between protein kinase C and the pleckstrin homology domain of Btk, terreic acid (TA) was identified and characterized in this study. This quinone epoxide specifically inhibited the enzymatic activity of Btk in mast cells and cell-free assays. TA faithfully recapitulated the phenotypic defects of btk mutant mast cells in high-affinity IgE receptor-stimulated wild-type mast cells without affecting the enzymatic activities and expressions of many other signaling molecules, including those of protein kinase C. Therefore, this study confirmed the important roles of Btk in mast cell functions and showed the usefulness of TA in probing into the functions of Btk in mast cells and other immune cell systems. Another insight obtained from this study is that the screening method used to identify TA is a useful approach to finding more efficacious Btk inhibitors. PMID:10051623

Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis.

PubMed

Antsiferova, Maria; Martin, Caroline; Huber, Marcel; Feyerabend, Thorsten B; Förster, Anja; Hartmann, Karin; Rodewald, Hans-Reimer; Hohl, Daniel; Werner, Sabine

2013-12-15

The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single- and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general.

Differences in irradiation susceptibility and turnover between mucosal and connective tissue-type mast cells of mice

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

Fukuzumi, T.; Waki, N.; Kanakura, Y.

Although precursors of mast cells are derived from the bone marrow, phenotypes of mast cells are influenced by the tissues in which final differentiation occurs. Connective tissue-type mast cells (CTMC) and mucosal mast cells (MMC) are different in morphological, biochemical, immunological, and functional criteria. The purpose of the present study was to obtain information about the differentiation process of MMC. First, we compared changes in irradiation susceptibility in mice during the differentiation process of CTMC and MMC. The decrease in irradiation susceptibility was remarkable in the CTMC differentiation process, but it was moderate in that of MMC. Some morphologically identifiablemore » CTMC in the peritoneal cavity had proliferative potential and were highly radioresistant, whereas such a radioresistant population of MMC was not detectable in the gastric mucosa. Second, we estimated the turnover of CTMC and MMC by determining the proportion of mast cells that were labeled with continuously administered bromodeoxyuridine. The turnover of MMC was significantly faster than that of CTMC. The absence of the radioresistant mast cell population in the gastric mucosa appeared to be related to the short life span of MMC.« less

Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils?

PubMed

Martins, Patrícia Rocha; Nascimento, Rodolfo Duarte; Lopes, Júlia Guimarães; Santos, Mônica Morais; de Oliveira, Cleida Aparecida; de Oliveira, Enio Chaves; Martinelli, Patrícia Massara; d'Ávila Reis, Débora

2015-05-01

Megacolon is frequently observed in patients who develop the digestive form of Chagas disease. It is characterized by dilation of the rectum-sigmoid portion and thickening of the colon wall. Microscopically, the affected organ presents denervation, which has been considered as consequence of an inflammatory process that begins at the acute phase and persists in the chronic phase of infection. Inflammatory infiltrates are composed of lymphocytes, macrophages, natural killer cells, mast cells, and eosinophils. In this study, we hypothesized that mast cells producing tryptase could influence the migration and the activation of eosinophils at the site, thereby contributing to the immunopathology of the chronic phase. We seek evidence of interactions between mast cells and eosinophils through (1) evaluation of eosinophils, regarding the expression of PAR2, a tryptase receptor; (2) correlation analysis between densities of mast cells and eosinophils; and (3) ultrastructural studies. The electron microscopy studies revealed signs of activation of mast cells and eosinophils, as well as physical interaction between these cells. Immunohistochemistry and correlation analyses point to the participation of tryptase immunoreactive mast cells in the migration and/or survival of eosinophils at the affected organ.

Quantification of mast cells in different stages of periodontal disease.

PubMed

Marjanović, Dragan; Andjelković, Zlatibor; Brkić, Zlata; Videnović, Goran; Šehalić, Meliha; Matvjenko, Vladimir; Leštarević, Snežana; Djordjević, Nadica

2016-05-01

Mast cells are mononuclear cells originating from bone marrow. They produce various biologically active substances, which allow them to actively participate in immune and inflammatory processes associated with periodontal disease. The study focused on distribution and density of mast cells in healthy gingiva as well as in different stages of periodontal disease. The material used for this purpose was gingival biopsies taken from 96 patients classified into 4 groups: healthy gingiva, gingivitis, initial and severe periodontal disease. Toluidine blue staining according to Spicer was utilized for identifying mast cells. Basing on our study, the density of mast cells in the gingival tissue increases with the progression of the infection, which means they are more numerous in gingivitis compared to healthy gingiva, as well as in periodontal disease compared to gingivitis. Increase in the number of mast cells in the infected gingiva can be correlated with an increased influx of inflammatory cells from blood circulation into the gingival stroma, as well as with the collagen lysis, since these cells produce substances with collagenolytic potential. Based on the distribution of mast cells, it could be concluded that in the evolution of periodontal disease there are significant dynamic alterations in migration and localization of these cells.

The anti-allergic compound tranilast attenuates inflammation and inhibits bone destruction in collagen-induced arthritis in mice

PubMed Central

Shiota, N; Kovanen, PT; Eklund, KK; Shibata, N; Shimoura, K; Niibayashi, T; Shimbori, C; Okunishi, H

2010-01-01

Background and purpose: Recent findings suggest the importance of mast cells in the pathogenesis of rheumatoid arthritis and their potential as a therapeutic target. Tranilast is an anti-allergic compound with a potent membrane-stabilizing effect on mast cells and a wide range of anti-inflammatory effects, thus may be advantageous in the treatment of arthritis. Here, we have evaluated the effects of tranilast on the progression of collagen-induced arthritis in mice. Experimental approach: Tranilast (400 mg·kg−1·day−1) was orally administered for 8 weeks to mice with established collagen-induced arthritis. Arthritis was assessed by clinical signs and X-ray scores. In paw tissue, the numbers of mast cells and osteoclasts were measured by histological analysis, and several inflammatory factors were assessed by RT-PCR and Western blot analysis.* Key results: TNF-α-positive mast cells were present extensively throughout the inflamed synovium of vehicle-treated arthritic mice, with some mast cells in close proximity to osteoclasts in areas of marked bone and cartilage destruction. Tranilast significantly reduced clinical and X-ray scores of arthritis and decreased numbers of TNF-α-positive mast cells and mRNA levels of TNF-α, chymase (mouse mast cell protease 4), tryptase (mouse mast cell protease 6), stem cell factor, interleukin-6, cathepsin-K, receptor activator of nuclear factor-κB, and of receptor activator of nuclear factor-κB-ligand, but increased interleukin-10 mRNA level in paws of arthritic mice. Osteoclast numbers were decreased by treatment with tranilast. Conclusions and implications: Tranilast possesses significant anti-rheumatic efficacy and, probably, this therapeutic effect is partly mediated by inhibition of mast cell activation and osteoclastogenesis. PMID:20067475

Critical role of tissue mast cells in controlling long-term glucose sensor function in vivo.

PubMed

Klueh, Ulrike; Kaur, Manjot; Qiao, Yi; Kreutzer, Donald L

2010-06-01

Little is known about the specific cells, mediators and mechanisms involved in the loss of glucose sensor function (GSF) in vivo. Since mast cells (MC) are known to be key effector cells in inflammation and wound healing, we hypothesized that MC and their products are major contributors to the skin inflammation and wound healing that controls GSF at sites of sensor implantation. To test this hypothesis we utilized a murine model of continuous glucose monitoring (CGM) in vivo in both normal C57BL/6 mice (mast cell sufficient), as well as mast cell deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (Sash) mice over a 28 day CGM period. As expected, both strains of mice displayed excellent CGM for the first 7 days post sensor implantation (PSI). CGM in the mast cell sufficient C57BL/6 mice was erratic over the remaining 21 days PSI. CGM in the mast cell deficient Sash mice displayed excellent sensor function for the entire 28 day of CGM. Histopathologic evaluation of implantation sites demonstrated that tissue reactions in Sash mice were dramatically less compared to the reactions in normal C57BL/6 mice. Additionally, mast cells were also seen to be consistently associated with the margins of sensor tissue reactions in normal C57BL/6 mice. Finally, direct injection of bone marrow derived mast cells at sites of sensor implantation induced an acute and dramatic loss of sensor function in both C57BL/6 and Sash mice. These results demonstrate the key role of mast cells in controlling glucose sensor function in vivo. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Pyruvate dehydrogenase has a major role in mast cell function, and its activity is regulated by mitochondrial microphthalmia transcription factor.

PubMed

Sharkia, Israa; Hadad Erlich, Tal; Landolina, Nadine; Assayag, Miri; Motzik, Alex; Rachmin, Inbal; Kay, Gillian; Porat, Ziv; Tshori, Sagi; Berkman, Neville; Levi-Schaffer, Francesca; Razin, Ehud

2017-07-01

We have recently observed that oxidative phosphorylation-mediated ATP production is essential for mast cell function. Pyruvate dehydrogenase (PDH) is the main regulator of the Krebs cycle and is located upstream of the electron transport chain. However, the role of PDH in mast cell function has not been described. Microphthalmia transcription factor (MITF) regulates the development, number, and function of mast cells. Localization of MITF to the mitochondria and its interaction with mitochondrial proteins has not been explored. We sought to explore the role played by PDH in mast cell exocytosis and to determine whether MITF is localized in the mitochondria and involved in regulation of PDH activity. Experiments were performed in vitro by using human and mouse mast cells, as well as rat basophil leukemia cells, and in vivo in mice. The effect of PDH inhibition on mast cell function was examined. PDH interaction with MITF was measured before and after immunologic activation. Furthermore, mitochondrial localization of MITF and its effect on PDH activity were determined. PDH is essential for immunologically mediated degranulation of mast cells. After activation, PDH is serine dephosphorylated. In addition, for the first time, we show that MITF is partially located in the mitochondria and interacts with PDH. This interaction is dependent on the phosphorylation state of PDH. Furthermore, mitochondrial MITF regulates PDH activity. The association of mitochondrial MITF with PDH emerges as an important regulator of mast cell function. Our findings indicate that PDH could arise as a new target for the manipulation of allergic diseases. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Circulating Immunoglobulins Are Not Associated with Intraplaque Mast Cell Number and Other Vulnerable Plaque Characteristics in Patients with Carotid Artery Stenosis

PubMed Central

Quax, Paul H. A.; de Borst, Gert Jan; de Vries, Jean-Paul P. M.; Moll, Frans L.; Kuiper, Johan; Toes, René E. M.; de Jager, Saskia C. A.; de Kleijn, Dominique P. V.; Hoefer, Imo E.; Pasterkamp, Gerard; Bot, Ilze

2014-01-01

Background Recently, we have shown that intraplaque mast cell numbers are associated with atherosclerotic plaque vulnerability and with future cardiovascular events, which renders inhibition of mast cell activation of interest for future therapeutic interventions. However, the endogenous triggers that activate mast cells during the progression and destabilization of atherosclerotic lesions remain unidentified. Mast cells can be activated by immunoglobulins and in the present study, we aimed to establish whether specific immunoglobulins in plasma of patients scheduled for carotid endarterectomy were related to (activated) intraplaque mast cell numbers and plasma tryptase levels. In addition, the levels were related to other vulnerable plaque characteristics and baseline clinical data. Methods and Results OxLDL-IgG, total IgG and total IgE levels were measured in 135 patients who underwent carotid endarterectomy. No associations were observed between the tested plasma immunoglobulin levels and total mast cell numbers in atherosclerotic plaques. Furthermore, no associations were found between IgG levels and the following plaque characteristics: lipid core size, degree of calcification, number of macrophages or smooth muscle cells, amount of collagen and number of microvessels. Interestingly, statin use was negatively associated with plasma IgE and oxLDL-IgG levels. Conclusions In patients suffering from carotid artery disease, total IgE, total IgG and oxLDL-IgG levels do not associate with plaque mast cell numbers or other vulnerable plaque histopathological characteristics. This study thus does not provide evidence that the immunoglobulins tested in our cohort play a role in intraplaque mast cell activation or grade of atherosclerosis. PMID:24586471

Altered expression of IL-18 binding protein and IL-18 receptor in basophils and mast cells of asthma patients.

PubMed

Wang, Zhiyun; Liu, Zhining; Wang, Ling; Wang, Junling; Chen, Liping; Xie, Hua; Zhang, Huiyun; He, Shaoheng

2018-05-01

IL-18 is likely to contribute to asthma. However, little is known regarding the role of IL-18 binding protein (BP) and IL-18 receptor (R) in asthma. Because the action of IL-18 in the body is regulated by IL-18BP and mast cells and basophils are key cell types involved in asthma, we investigated the expression of IL-18, IL-18BP and IL-18R in basophils and mast cells using flow cytometry and a mouse asthma model. We found that among basophils, approximately 53% and 51% were IL-18 + , 85% and 81% were IL-18BP + basophils, and 19.8% and 8.6% were IL-18R + in healthy control (HC) and asthmatic blood, respectively. The allergens tested had little effect on the expression of IL-18 and related factors. Only 3.5%, 14.3% and 2.4% of dispersed mast cells expressed IL-18, IL-18BP and IL-18R, respectively, in asthmatic sputum. In a mouse asthma model, OVA-sensitized mice exhibited decreased IL-18BP + but increased IL-18R + basophils in their blood. IL-18 increased the number of basophils but eliminated IL-18BP + basophils in mouse blood. IL-18 increased the number of mast cells and IL-18R + mast cells in the lung as well as increased the mast cell numbers and IL-18BP + mast cells in the bronchoalveolar lavage fluid (BALF) of OVA-sensitized mice. Thus, basophils and mast cells may be involved in asthma pathogenesis via an IL-18-associated mechanism. © 2018 The Foundation for the Scandinavian Journal of Immunology.

Anaphylaxis as a clinical manifestation of clonal mast cell disorders.

PubMed

Matito, A; Alvarez-Twose, I; Morgado, J M; Sánchez-Muñoz, L; Orfao, A; Escribano, L

2014-08-01

Clonal mast cell disorders comprise a heterogeneous group of disorders characterized by the presence of gain of function KIT mutations and a constitutively altered activation-associated mast cell immunophenotype frequently associated with clinical manifestations related to the release of mast cells mediators. These disorders do not always fulfil the World Health Organization (WHO)-proposed criteria for mastocytosis, particularly when low-sensitive diagnostic approaches are performed. Anaphylaxis is a frequent presentation of clonal mast cell disorders, particularly in mastocytosis patients without typical skin lesions. The presence of cardiovascular symptoms, e.g., hypotension, occurring after a hymenoptera sting or spontaneously in the absence of cutaneous manifestations such as urticaria is characteristic and differs from the presentation of anaphylaxis in the general population without mastocytosis.

Dengue Virus Infection of Mast Cells Triggers Endothelial Cell Activation ▿

PubMed Central

Brown, Michael G.; Hermann, Laura L.; Issekutz, Andrew C.; Marshall, Jean S.; Rowter, Derek; Al-Afif, Ayham; Anderson, Robert

2011-01-01

Vascular perturbation is a hallmark of severe forms of dengue disease. We show here that antibody-enhanced dengue virus infection of primary human cord blood-derived mast cells (CBMCs) and the human mast cell-like line HMC-1 results in the release of factor(s) which activate human endothelial cells, as evidenced by increased expression of the adhesion molecules ICAM-1 and VCAM-1. Endothelial cell activation was prevented by pretreatment of mast cell-derived supernatants with a tumor necrosis factor (TNF)-specific blocking antibody, thus identifying TNF as the endothelial cell-activating factor. Our findings suggest that mast cells may represent an important source of TNF, promoting vascular endothelial perturbation following antibody-enhanced dengue virus infection. PMID:21068256

125. HYDRAULIC CONTROLS FOR MAST TRENCH DOORS ON LEFT SIDE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

125. HYDRAULIC CONTROLS FOR MAST TRENCH DOORS ON LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

The 17th Aerospace Mechanisms Symposium

NASA Technical Reports Server (NTRS)

1983-01-01

The proceedings of the Aerospace Mechanisms Symposium are reported. Technological areas covered include space lubrication, aerodynamic devices, spacecraft/Shuttle latches, deployment, positioning, and pointing. Devices for spacecraft tether, magnetic bearing suspension, explosive welding, and a deployable/retractable mast are also described.

Deep-Sea-Derived Butyrolactone I Suppresses Ovalbumin-Induced Anaphylaxis by Regulating Mast Cell Function in a Murine Model.

PubMed

Liu, Qing-Mei; Xie, Chun-Lan; Gao, Yuan-Yuan; Liu, Bo; Lin, Wei-Xiang; Liu, Hong; Cao, Min-Jie; Su, Wen-Jin; Yang, Xian-Wen; Liu, Guang-Ming

2018-06-06

Deep-sea-derived butyrolactone I (BTL-I), which was identified as a type of butanolide, was isolated from Aspergillus sp. Ovalbumin (OVA)-induced BALB/c anaphylaxis was established to explore the antifood allergic activity of BTL-I. As a result, BTL-I was able to alleviate OVA-induced allergy symptoms, reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and decrease the population of mast cells in the spleen and mesenteric lymph nodes. BTL-I also significantly suppressed mast-dependent passive cutaneous anaphylaxis. Additionally, the maturation of bone marrow-derived mast cells (BMMCs) declined as BTL-I caused down-regulation of c-KIT receptors. Furthermore, molecular docking analyses revealed that BTL-I interacted with the inhibitory receptor, FcγRIIB. In conclusion, the reduction of mast cell function by deep-sea-derived BTL-I as well as its interactions with the inhibitory receptor, FcγRIIB, may contribute to BTL-I-related protection against food anaphylaxis.

Role of thrombopoietin in mast cell differentiation.

PubMed

Migliaccio, Anna Rita; Rana, Rosa Alba; Vannucchi, Alessandro M; Manzoli, Francesco A

2007-06-01

Mast cells are important elements of the body response to foreign antigens, being those represented either by small molecules (allergic response) or harbored by foreign microorganisms (response to parasite infection). These cells derive from hematopoietic stem/progenitor cells present in the marrow. However, in contrast with most of the other hematopoietic lineages, mast cells do not differentiate in the marrow but in highly vascularized extramedullary sites, such as the skin or the gut. Mast cell differentiation in the marrow is activated as part of the body response to parasites. We will review here the mast cell differentiation pathway and what is known of its major intrinsic and extrinsic control mechanisms. It will also be described that thrombopoietin, the ligand for the Mpl receptor, in addition to its pivotal rule in the control of thrombocytopoiesis and of hematopoietic stem/progenitor cell proliferation, exerts a regulatory function in mast cell differentiation. Some of the possible implications of this newly described biological activity of thrombopoietin will be discussed.

Hematopoietic Kit Deficiency, rather than Lack of Mast Cells, Protects Mice from Obesity and Insulin Resistance.

PubMed

Gutierrez, Dario A; Muralidhar, Sathya; Feyerabend, Thorsten B; Herzig, Stephan; Rodewald, Hans-Reimer

2015-05-05

Obesity, insulin resistance, and related pathologies are associated with immune-mediated chronic inflammation. Kit mutant mice are protected from diet-induced obesity and associated co-morbidities, and this phenotype has previously been attributed to their lack of mast cells. We performed a comprehensive metabolic analysis of Kit-dependent Kit(W/Wv) and Kit-independent Cpa3(Cre/+) mast-cell-deficient mouse strains, employing diet-induced or genetic (Lep(Ob/Ob) background) models of obesity. Our results show that mast cell deficiency, in the absence of Kit mutations, plays no role in the regulation of weight gain or insulin resistance. Moreover, we provide evidence that the metabolic phenotype observed in Kit mutant mice, while independent of mast cells, is immune regulated. Our data underscore the value of definitive mast cell deficiency models to conclusively test the involvement of this enigmatic cell in immune-mediated pathologies and identify Kit as a key hematopoietic factor in the pathogenesis of metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis.

PubMed

Piliponsky, Adrian M; Chen, Ching-Cheng; Nishimura, Toshihiko; Metz, Martin; Rios, Eon J; Dobner, Paul R; Wada, Etsuko; Wada, Keiji; Zacharias, Sherma; Mohanasundaram, Uma M; Faix, James D; Abrink, Magnus; Pejler, Gunnar; Pearl, Ronald G; Tsai, Mindy; Galli, Stephen J

2008-04-01

Sepsis is a complex, incompletely understood and often fatal disorder, typically accompanied by hypotension, that is considered to represent a dysregulated host response to infection. Neurotensin (NT) is a 13-amino-acid peptide that, among its multiple effects, induces hypotension. We find that intraperitoneal and plasma concentrations of NT are increased in mice after severe cecal ligation and puncture (CLP), a model of sepsis, and that mice treated with a pharmacological antagonist of NT, or NT-deficient mice, show reduced mortality during severe CLP. In mice, mast cells can degrade NT and reduce NT-induced hypotension and CLP-associated mortality, and optimal expression of these effects requires mast cell expression of neurotensin receptor 1 and neurolysin. These findings show that NT contributes to sepsis-related mortality in mice during severe CLP and that mast cells can lower NT concentrations, and suggest that mast cell-dependent reduction in NT levels contributes to the ability of mast cells to enhance survival after CLP.

Spatiotemporally and Mechanically Controlled Triggering of Mast Cells using Atomic Force Microscopy

PubMed Central

Hu, Kenneth K.; Bruce, Marc A.; Butte, Manish J.

2014-01-01

Mast cells are thought to be sensitive to mechanical forces, for example, coughing in asthma or pressure in “physical urticarias”. Conversion of mechanical forces to biochemical signals could potentially augment antigenic signaling. Studying the combined effects of mechanical and antigenic cues on mast cells and other hematopoietic cells has been elusive. Here, we present an approach using a modified atomic force microscope cantilever to deliver antigenic signals to mast cells while simultaneously applying mechanical forces. We developed a strategy to concurrently record degranulation events by fluorescence microscopy during antigenic triggering. Finally, we also measured the mechanical forces generated by mast cells while antigen receptors are ligated. We showed that mast cells respond to antigen delivered by the AFM cantilever with prompt degranulation and the generation of strong pushing and pulling forces. We did not discern any relationship between applied mechanical forces and the kinetics of degranulation. These experiments present a new method for dissecting the interactions of mechanical and biochemical cues in signaling responses of immune cells. PMID:24777418

Is self-reported height or arm span a more accurate alternative measure of height?

PubMed

Brown, Jean K; Feng, Jui-Ying; Knapp, Thomas R

2002-11-01

The purpose of this study was to determine whether self-reported height or arm span is the more accurate alternative measure of height. A sample of 409 people between the ages of 19 and 67 (M = 35.0) participated in this anthropometric study. Height, self-reported height, and arm span were measured by 82 nursing research students. Mean differences from criterion measures were 0.17 cm for the measuring rules, 0.47 cm for arm span, and 0.85 cm and 0.87 cm for heights. Test-retest reliability was r = .997 for both height and arm span. The relationships of height to self-reported height and arm span were r = .97 and .90, respectively. Mean absolute differences were 1.80 cm and 4.29 cm, respectively. These findings support the practice of using self-reported height as an alternative measure of measured height in clinical settings, but arm span is an accurate alternative when neither measured height nor self-reported height is obtainable.

Mast Cell Dependent Vascular Changes Associated with an Acute Response to Cold Immersion in Primary Contact Urticaria

PubMed Central

Meyer, Joseph; Gorbach, Alexander M.; Liu, Wei-Min; Medic, Nevenka; Young, Michael; Nelson, Celeste; Arceo, Sarah; Desai, Avanti; Metcalfe, Dean D.; Komarow, Hirsh D.

2013-01-01

Background While a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation. Objective To characterize the microcirculatory events that follow mast cell degranulation. Methodology/Principal Findings Perturbations in dermal blood flow, temperature and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI) challenge in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the histamine-associated vascular response accompanying mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an antihistamine. Conclusions/Significance Monitoring the hemodynamic responses within tissues that are associated with mast cell degranulation provides additional insight into the evolution of the acute inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention. PMID:23451084

Comparison of Mast Cells Count in Odontogenic Cysts Using Histochemical Staining.

PubMed

Rajabi-Moghaddam, Mahdieh; Abbaszadeh-Bidokhty, Hamid; Bijani, Ali

2015-01-01

Odontogenic cysts are among the most frequent destructive lesions of jaws which their pathogenesis and growth mechanism are not cleared. With respect to different roles of mast cells, they may play a role in the pathogenesis and growth of odontogenic cysts. The aim of present study was to evaluate mast cells in the most common odontogenic cyst. Thirty paraffin-embedded tissue blocks including 10 radicular cysts, 10 dentigerous cysts and 10 odontogenic keratocysts were used and 5 micron sections stained with toluidine blue and observed by light microscope under ×400 magnification to evaluate mast cells within these cysts. For each case, 5 high-power field areas, selected from hot-spot areas, were considered and each area divided into 3 zones: intra-epithelial zone, sub-epithelial zone and deep zone. Most of the studied cyst showed presence of mast cells. There was not any significant difference in mast cell count between studied cysts ( P -values > 0.05).With respect to intra-epithelial, sub-epithelial and deep zones, there was not any significant difference between three studied cysts. There was not any significant difference between sub-epithelial zone and deep zone within each of these cysts. There was only significant difference between intra-epithelial zone and sub-epithelial zone within dentigerous cysts and odontogenic keratocysts ( P -value < 0.05). Prevalence of mast cells in fibrous wall of odontogenic cysts suggests their activity in these cysts. Mast cells may not be directly involved in the pathogenesis of odontogenic keratocysts.

Mast cells are dispensable in a genetic mouse model of chronic dermatitis.

PubMed

Sulcova, Jitka; Meyer, Michael; Guiducci, Eva; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Werner, Sabine

2015-06-01

Chronic inflammatory skin diseases, such as atopic dermatitis, affect a large percentage of the population, but the role of different immune cells in the pathogenesis of these disorders is largely unknown. Recently, we found that mice lacking fibroblast growth factor receptor 1 (Fgfr1) and Fgfr2 (K5-R1/R2 mice) in the epidermis have a severe impairment in the epidermal barrier, which leads to the development of a chronic inflammatory skin disease that shares many features with human atopic dermatitis. Using Fgfr1-/Fgfr2-deficient mice, we analyzed the consequences of the loss of mast cells. Mast cells accumulated and degranulated in the skin of young Fgfr1-/Fgfr2-deficient mice, most likely as a consequence of increased expression of the mast cell chemokine Ccl2. The increase in mast cells occurred before the development of histological abnormalities, indicating a functional role of these cells in the inflammatory skin phenotype. To test this hypothesis, we mated the Fgfr1-/Fgfr2-deficient mice with mast cell-deficient CreMaster mice. Surprisingly, loss of mast cells did not or only mildly affect keratinocyte proliferation, epidermal thickness, epidermal barrier function, accumulation and activation of different immune cells, or expression of different proinflammatory cytokines in the skin. These results reveal that mast cells are dispensable for the development of chronic inflammation in response to a defect in the epidermal barrier. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells.

PubMed

Hu Frisk, Jun Mei; Kjellén, Lena; Kaler, Stephen G; Pejler, Gunnar; Öhrvik, Helena

2017-12-15

Copper has previously been implicated in the regulation of immune responses, but the impact of this metal on mast cells is poorly understood. In this article, we address this issue and show that copper starvation of mast cells causes increased granule maturation, as indicated by higher proteoglycan content, stronger metachromatic staining, and altered ultrastructure in comparison with nontreated cells, whereas copper overload has the opposite effects. In contrast, copper status did not impact storage of histamine in mast cells, nor did alterations in copper levels affect the ability of mast cells to degranulate in response to IgER cross-linking. A striking finding was decreased tryptase content in mast cells with copper overload, whereas copper starvation increased tryptase content. These effects were associated with corresponding shifts in tryptase mRNA levels, suggesting that copper affects tryptase gene regulation. Mechanistically, we found that alterations in copper status affected the expression of microphthalmia-associated transcription factor, a transcription factor critical for driving tryptase expression. We also found evidence supporting the concept that the effects on microphthalmia-associated transcription factor are dependent on copper-mediated modulation of MAPK signaling. Finally, we show that, in MEDNIK syndrome, a condition associated with low copper levels and a hyperallergenic skin phenotype, including pruritis and dermatitis, the number of tryptase-positive mast cells is increased. Taken together, our findings reveal a hitherto unrecognized role for copper in the regulation of mast cell gene expression and maturation. Copyright © 2017 by The American Association of Immunologists, Inc.

The Tropospheric cooling and the Stratospheric warming at Tirunelveli during the Annular Solar Eclipse of 15 January, 2010

NASA Astrophysics Data System (ADS)

Nelli, Narendra Reddy; Choudhary, Raj Kumar; Rao, Kusuma

The UTLS region, a transition region between the troposphere and the stratosphere is of concern to climate scientists as its temperature variations are crucial in determining the water vapour and the other trace gases transport between the two regions, which inturn determine the radiative warming and cooling of the troposphere and the stratosphere. To examine, the temperature variations from surface to lower stratosphere,a major experiment facility was set up for upper air and surface measurements during the Annular Solar Eclipse (ASE) of January 15, 2010 at Tirunelveli (8.72 N, 77.81 E) located in 94% eclipse path in the southern peninsular India. The instruments,namely, 1. high resolution GPS radiosonde system, 2. an instrumented 15 m high Mini Boundary Layer Mast, 3. an instrumented 1 m high Near Surface Mast (NSM), radiation and other ground sensors were operated during the period 14-19 Jan, 2010. The ASE of January 15, 2010 was unique being the longest in duration (9 min, 15.3 sec) among the similar ones that occurred in the past. The major inference from an analysis of surface and upper air measurements is the occurrence of troposphere cooling during the eclipse with the peak cooling of 5 K at 15 km height with respect to no-eclispe conditions. Also, intense warming in the stratosphere is observed with the peak warming of 7 K at 19 km height.Cooling of the Troposphere as the eclipse advanced and the revival to its normal temperature is clearly captured in upper air measurements. The downward vertical velocities observed at 100 hPa in NCEP Re-analyses, consistent with the tropospheric cooling during the ASE window, may be causing the stratospheric warming. Partly, these vertical velocities could be induced by the mesoscale circulation associated with the mesoscale convective system that prevailed parallel to the eclipse path as described in METEOSAT imageries of brightness temperatures from IR channel. Further analysis is being carried out to quantify the variations in turbulent parameters during ASE window using the high resolution GPS Radiosonde data.

Study of the effects of wind power and vortex-induced vibrations to establish fatigue design criteria for high-mast poles.

DOT National Transportation Integrated Search

2011-08-01

Traffic signal and high-mast poles are used by transportation agencies to control and illuminate intersections; their structural design is governed by national specifications. High-mast poles are luminaire supports located near highway interchanges t...

126. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

126. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

109. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

109. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (109), LSB (BLDG. 770) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

41. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM LAUNCHER; ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

41. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM LAUNCHER; SOUTH FACE OF MST IN BACKGROUND. RAIL SYSTEM FROM BASE OF MST PARALLEL TO MAST. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Analysis and characterization of the vertical wind profile in UAE

NASA Astrophysics Data System (ADS)

Lee, W.; Ghedira, H.; Ouarda, T.; Gherboudj, I.

2011-12-01

In this study, temporal and spatial analysis of the vertical wind profiles in the UAE has been performed to estimate wind resource potential. Due to the very limited number of wind masts (only two wind masts in the UAE, operational for less than three years), the wind potential analysis will be mainly derived from numerical-based models. Additional wind data will be derived from the UAE met stations network (at 10 m elevation) managed by the UAE National Center of Meteorology and Seismology. However, since wind turbines are generally installed at elevations higher than 80 m, it is vital to extrapolate wind speed correctly from low heights to wind turbine hub heights to predict potential wind energy properly. To do so, firstly two boundary layer based models, power law and logarithmic law, were tested to find the best fitting model. Power law is expressed as v/v0 =(H/H0)^α and logarithmic law is represented as v/v0 =[ln(H/Z0))/(ln(H0/Z0)], where V is the wind speed [m/s] at height H [m] and V0 is the known wind speed at a reference height H0. The exponent (α) coefficient is an empirically derived value depending on the atmospheric stability and z0 is the roughness coefficient length [m] that depends on topography, land roughness and spacing. After testing the two models, spatial and temporal analysis for wind profile was performed. Many studies about wind in different regions have shown that wind profile parameters have hourly, monthly and seasonal variations. Therefore, it can be examined whether UAE wind characteristics follow general wind characteristics observed in other regions or have specific wind features due to its regional condition. About 3 years data from August 2008 to February 2011 with 10-minutes resolution were used to derive monthly variation. The preliminary results(Fig.1) show that during that period, wind profile parameters like alpha from power law and roughness length from logarithmic law have monthly variation. Both alpha and roughness have low values during summer and high values during winter. This variation is mainly explained by the direct effect of air temperature on atmospheric stability. When the surface temperature becomes high, air is mixed well in atmospheric boundary layer. This phenomenon leads to vertically low wind speed change indicating low wind profile parameter. On the contrary, cold surface temperature prevents air from being mixed well in the boundary layer. This analysis is applied to different regions to see the spatial characteristics of wind in UAE. As a next step, a mesoscale model coupled with UAE roughness maps will be used to predict elevated wind speed. A micro-scale modeling approach will be also used to capture small-scale wind speed variability. This data will be combined with the NCMS data and tailored to the UAE by modeling the effects due to local changes in terrain elevation and local surface roughness changes and obstacles.

Sexual Orientation, Objective Height, and Self-Reported Height.

PubMed

Skorska, Malvina N; Bogaert, Anthony F

2017-01-01

Studies that have used mostly self-reported height have found that androphilic men and women are shorter than gynephilic men and women, respectively. This study examined whether an objective height difference exists or whether a psychosocial account (e.g., distortion of self-reports) may explain these putative height differences. A total of 863 participants, recruited at a Canadian university, the surrounding region, and through lesbian, gay, bisexual, and transgender (LGBT) events across Canada, self-reported their height and had their height measured. Androphilic men were shorter, on average, than gynephilic men. There was no objective height difference between gynephilic, ambiphilic, and androphilic women. Self-reported height, statistically controlling for objective height, was not related to sexual orientation. These findings are the first to show an objective height difference between androphilic and gynephilic men. Also, the findings suggest that previous studies using self-reported height found part of a true objective height difference between androphilic and gynephilic men. These findings have implications for existing biological theories of men's sexual orientation development.

On the stability treatment in WAsP

NASA Astrophysics Data System (ADS)

Giebel, G.; Gryning, S.-E.

2003-04-01

An assessment of the treatment of atmospheric stability in the standard package for wind resource estimation, WAsP (from Risø National Laboratory), is presented. Emphasis is on the vertical wind profiles in WAsP and the treatment of stability therein, under special consideration of the nightly situation. The study starts with an introduction to WAsP and the way it treats the vertical extrapolation, under special consideration of the stability. The two parameters available for changing the stability treatment in WAsP are identified as RMS heat flux and offset heat flux. Four years worth of data from the meteorological mast at Risø, plus data from Egypt and Bermuda, is used for the identification of the parameter settings for stable conditions. To this aim, the measured heat fluxes from the mast were used to extract three data sets with successively higher stability in four different heights. These data sets were then run through the Observed Wind Climate Wizard (part of the WAsP package), resulting in Weibull fits to the data. Using these observed wind climates, a prediction of the highest level wind climate using the lowest level wind climate under all different stable conditions is undertaken and compared with the measured data set. To expand on this study, a systematic variation of the two heat flux parameters in WAsP is done, finding the parameters yielding the lowest overall errors for the predictions. Parts of this study were financed by the Landesumweltamt Brandenburg.

127. HYDRAULIC CONTROLS AND GAUGES FOR THE UMBILICAL MAST ON ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

127. HYDRAULIC CONTROLS AND GAUGES FOR THE UMBILICAL MAST ON UPPER RIGHT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

123. UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751). PUMP ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

123. UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751). PUMP ON LEFT; HYDRAULIC CONTROL PANEL FOR UMBILICAL MAST AND TRENCH DOORS IN CENTER OF ROOM, FACING WEST. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Application of rat mast cell incubates as a possible short-time test for sensitizing occupational chemicals.

PubMed

Diel, F; Neidhart, B; Oprée, W

1981-01-01

The direct action of sensitizing occupational chemicals (formaldehyde, phenol, phenylhydrazine, p-aminophenol) on rat mast cells was investigated by determination of histamine using HPLC separation and fluorimetric detection. It turned out that dispensed mast cells from immunized and non-immunized Wistar-rats are more sensitive than small-cut lung tissue slices. Passive cutaneous anaphylaxis was negative after a fortnight sensitizing experiment with the here described occupational chemicals. Short-time tests with rat mast cells reflect anaphylactoid response and are suitable for the screening of sensitizing chemicals.

Time domain modal identification/estimation of the mini-mast testbed

NASA Technical Reports Server (NTRS)

Roemer, Michael J.; Mook, D. Joseph

1991-01-01

The Mini-Mast is a 20 meter long 3-dimensional, deployable/retractable truss structure designed to imitate future trusses in space. Presented here are results from a robust (with respect to measurement noise sensitivity), time domain, modal identification technique for identifying the modal properties of the Mini-Mast structure even in the face of noisy environments. Three testing/analysis procedures are considered: sinusoidal excitation near resonant frequencies of the Mini-Mast, frequency response function averaging of several modal tests, and random input excitation with a free response period.

Effects of Secreted Mast Cell Mediators on Retinal Pigment Epithelial Cells: Focus on Mast Cell Tryptase.

PubMed

Arai, Rei; Usui-Ouchi, Ayumi; Ito, Yosuke; Mashimo, Keitaro; Murakami, Akira; Ebihara, Nobuyuki

2017-01-01

Numerous mast cells are present in the choroid, but the effects of mast cell mediators on retinal pigment epithelial (RPE) cells are not well understood. We investigated the influence of mast cell mediators on RPE cells in vitro, focusing on tryptase. Expression of receptors was examined by the reverse transcription polymerase chain reaction. We also assessed production of interleukin 8 and vascular endothelial growth factor (VEGF) after RPE cells were stimulated with mast cell mediators by using an antibody array and enzyme-linked immunosorbent assay. Furthermore, we investigated the influence of tryptase on RPE cell migration and integrity by the scratch assay and the transepithelial resistance. RPE cells expressed protease-activated receptor 2 (PAR2), histamine receptor 1, tumor necrosis factor- α (TNF- α ) receptor 1, and CCR 1, 3, 4, 8, and 11. Tryptase, PAR2 agonists, histamine, and TNF- α all enhanced interleukin 8 production by RPE cells, while only tryptase enhanced VEGF production. Tryptase also enhanced expression of phosphorylated extracellular signal-regulated kinases 1/2, resulting in increased migration of RPE cells. However, tryptase did not alter epithelial integrity or the expression of zonula occludens-1 and junctional adhesion molecule-A by RPE cells. Mast cell mediators, especially tryptase, may influence RPE cell inflammation.

Sympathetic Nervous System Modulation of Inflammation and Remodeling in the Hypertensive Heart

PubMed Central

Levick, Scott P.; Murray, David B.; Janicki, Joseph S.; Brower, Gregory L.

2010-01-01

Chronic activation of the sympathetic nervous system (SNS) is a key component of cardiac hypertrophy and fibrosis. However, previous studies have provided evidence to also implicate inflammatory cells, including mast cells, in the development of cardiac fibrosis. The current study investigated the potential interaction of cardiac mast cells with the SNS. Eight week old male SHR were sympathectomized to establish the effect of the SNS on cardiac mast cell density, myocardial remodeling and cytokine production in the hypertensive heart. Age-matched WKY served as controls. Cardiac fibrosis and hypertension were significantly attenuated and left ventricular mass normalized while cardiac mast cell density was markedly increased in sympathectomized SHR. Sympathectomy normalized myocardial levels of IFN-γ, IL-6 and IL-10, but had no effect on IL-4. The effect of norepinephrine and substance P on isolated cardiac mast cell activation was investigated as potential mechanisms of interaction between the two. Only substance P elicited mast cell degranulation. Substance P was also shown to induce the production of angiotensin II by a mixed population of isolated cardiac inflammatory cells, including mast cells, lymphocytes and macrophages. These results demonstrate the ability of neuropeptides to regulate inflammatory cell function, providing a potential mechanism by which the SNS and afferent nerves may interact with inflammatory cells in the hypertensive heart. PMID:20048196

Redox regulation of mast cell histamine release in thioredoxin-1 (TRX) transgenic mice.

PubMed

Son, Aoi; Nakamura, Hajime; Kondo, Norihiko; Matsuo, Yoshiyuki; Liu, Wenrui; Oka, Shin-ichi; Ishii, Yasuyuki; Yodoi, Junji

2006-02-01

Thioredoxin-1 (TRX) is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affinity receptor for IgE (FcepsilonRI) was significantly suppressed in TRX transgenic (TRX-tg) mice compared to wild type (WT) mice. Intracellular reactive oxygen species (ROS) of mast cells stimulated by IgE and antigen was also reduced in TRX-tg mice compared to WT mice. Whereas there was no difference in the production of cytokines (IL-6 and TNF-alpha) from mast cells in response to 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulation in TRX-tg and WT mice. Immunological status of TRX-tg mice inclined to T helper (Th) 2 dominant in primary immune response, although there was no difference in the population of dendritic cells (DCs) and regulatory T cells. We conclude that the histamine release from mast cells in TRX-tg mice is suppressed by inhibition of ROS generation. As ROS are involved in mast cell activation and facilitate mediator release, TRX may be a key signaling molecule regulating the early events in the IgE signaling in mast cells and the allergic inflammation.

Increased Bone Mass in Female Mice Lacking Mast Cell Chymase

PubMed Central

Lind, Thomas; Gustafson, Ann-Marie; Calounova, Gabriela; Hu, Lijuan; Rasmusson, Annica; Jonsson, Kenneth B.; Wernersson, Sara; Åbrink, Magnus; Andersson, Göran; Larsson, Sune; Melhus, Håkan; Pejler, Gunnar

2016-01-01

Here we addressed the potential impact of chymase, a mast-cell restricted protease, on mouse bone phenotype. We show that female mice lacking the chymase Mcpt4 acquired a persistent expansion of diaphyseal bone in comparison with wild type controls, reaching a 15% larger diaphyseal cross sectional area at 12 months of age. Mcpt4-/- mice also showed increased levels of a bone anabolic serum marker and higher periosteal bone formation rate. However, they were not protected from experimental osteoporosis, suggesting that chymase regulates normal bone homeostasis rather than the course of osteoporosis. Further, the absence of Mcpt4 resulted in age-dependent upregulation of numerous genes important for bone formation but no effects on osteoclast activity. In spite of the latter, Mcpt4-/- bones had increased cortical porosity and reduced endocortical mineralization. Mast cells were found periosteally and, notably, bone-proximal mast cells in Mcpt4-/- mice were degranulated to a larger extent than in wild type mice. Hence, chymase regulates degranulation of bone mast cells, which could affect the release of mast cell-derived factors influencing bone remodelling. Together, these findings reveal a functional impact of mast cell chymase on bone. Further studies exploring the possibility of using chymase inhibitors as a strategy to increase bone volume may be warranted. PMID:27936149

Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation

PubMed Central

Nizamutdinova, Irina Tsoy; Dusio, Giuseppina F.; Gasheva, Olga Yu.; Skoog, Hunter; Tobin, Richard; Peddaboina, Chander; Meininger, Cynthia J.; Zawieja, David C.; Newell-Rogers, M. Karen; Gashev, Anatoliy A.

2016-01-01

This study aimed to establish mechanistic links between the aging-associated changes in the functional status of mast cells and the altered responses of mesenteric tissue and mesenteric lymphatic vessels (MLVs) to acute inflammation. We used an in vivo model of acute peritoneal inflammation induced by lipopolysaccharide treatment of adult (9-month) and aged (24-month) F-344 rats. We analyzed contractility of isolated MLVs, mast cell activation, activation of nuclear factor-κB (NF-κB) without and with stabilization of mast cells by cromolyn or blockade of all types of histamine receptors and production of 27 major pro-inflammatory cytokines in adult and aged perilymphatic mesenteric tissues and blood. We found that the reactivity of aged contracting lymphatic vessels to LPS-induced acute inflammation was abolished and that activated mast cells trigger NF-κB signaling in the mesentery through release of histamine. The aging-associated basal activation of mesenteric mast cells limits acute inflammatory NF-κB activation in aged mesentery. We conclude that proper functioning of the mast cell/histamine/NF-κB axis is necessary for reactions of the lymphatic vessels to acute inflammatory stimuli as well as for interaction and trafficking of immune cells near and within the collecting lymphatics. PMID:27875806

[Effect of a proteinase-activated receptor-2 (PAR-2) agonist on tryptase release from human mast cells].

PubMed

He, Shao-Heng; Xie, Hua; He, Yong-Song

2002-12-25

Proteinase-activated receptor-2 (PAR-2) expression has been observed on numerous cell types. However, little is known about the functional expression of PAR-2 in human mast cells. In the current study, the actions of a PAR-2 agonist trans-cinnamoyl-Leu-Ile-Gly-Arg-Leu-Orn-amide (tc-LIGRLO) on tryptase release from dispersed human colonic mast cells were examined. The results showed that tc-LIGRLO was able to induce a fold increase in tryptase release over the basal level following a 15 min incubation of colonic mast cells, whereas tc-OLRGIL did not have any effect on tryptase release. The potency of tc-LIGRLO appeared greater than that of anti-IgE and calcium ionophore A23187 (CI) in induction of tryptase release. Extending the incubation time to 30 min had no significant effect on the actions of tc-LIGRLO or anti-IgE. In the time course study, it was observed that the tryptase release from mast cells induced by tc-LIGRLO started at 1 min and peaked at 3 min following incubation. The above-mentioned results indicate that tc-LIGRLO is a potent stimulus of tryptase release from human mast cells, which strongly suggests that PAR-2s are expressed in human mast cells.

Evaluating the Role of Immunological Cells (Tissue Eosinophils and Mast Cells) in Progression of Oral Squamous Cell Carcinoma.

PubMed

Saxena, S; Singh, A; Singh, P; Sundaragiri, K S; Sankhla, B; Bhargava, A

2018-04-01

Mast cells and eosinophils are increased in oral squamous cell carcinoma. The significance of such an association has been variably thought to be either a potential diagnostic tool for stromal invasion or as a prognostic indicator. The aim of the study was to study the mast cells and eosinophils between normal oral mucosa, leukoplakia and oral squamous cell carcinoma and to study the significance of mast cells in the progression of the lesion. A retrospective study was done on archival tissue received from January 2015 to December 2015, in the Department of Oral Pathology, RUHS College of Dental Sciences, Jaipur, Rajasthan, India. Seventy (70) cases were studied (30 cases each of leukoplakia and carcinoma and 10 cases of control group), sections were stained with toluidine blue solution to reveal mast cells. Eosinophils were studied in Haematoxylin & Eosin stained sections. Mast cell density significantly increased from: normal mucosa to oral leukoplakia to carcinoma, suggesting a role of the mast cells in the development of these lesions. The higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion. The assessment of these could become, in the future, useful for therapeutic approaches in this subset of the patient.

Evidence for mast cells contributing to neuromuscular pathology in an inherited model of ALS

PubMed Central

Trias, Emiliano; Ibarburu, Sofía; Barreto-Núñez, Romina; Varela, Valentina; Moura, Ivan C.; Hermine, Olivier

2017-01-01

Evidence indicates that neuroinflammation contributes to motor neuron degeneration in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease leading to progressive muscular paralysis. However, it remains elusive whether inflammatory cells can interact with degenerating distal motor axons, influencing the progressive denervation of neuromuscular junctions (NMJs). By analyzing the muscle extensor digitorum longus (EDL) following paralysis onset in the SOD1G93A rat model, we have observed a massive infiltration and degranulation of mast cells, starting after paralysis onset and correlating with progressive NMJ denervation. Remarkably, mast cells accumulated around degenerating motor axons and NMJs, and were also associated with macrophages. Mast cell accumulation and degranulation in paralytic EDL muscle was prevented by systemic treatment over 15 days with masitinib, a tyrosine kinase inhibitor currently in clinical trials for ALS exhibiting pharmacological activity affecting mast cells and microglia. Masitinib-induced mast cell reduction resulted in a 35% decrease in NMJ denervation and reduced motor deficits as compared with vehicle-treated rats. Masitinib also normalized macrophage infiltration, as well as regressive changes in Schwann cells and capillary networks observed in advanced paralysis. These findings provide evidence for mast cell contribution to distal axonopathy and paralysis progression in ALS, a mechanism that can be therapeutically targeted by masitinib. PMID:29046475

A new automated multiple allergen simultaneous test-chemiluminescent assay (MAST-CLA) using an AP720S analyzer.

PubMed

Lee, Sungsil; Lim, Hwan Sub; Park, Jungyong; Kim, Hyon Suk

2009-04-01

In the diagnosis of atopic diseases, allergen detection is a crucial step. Multiple allergen simultaneous test-chemiluminescent assay (MAST-CLA) is a simple and noninvasive method for in vitro screening of allergen-specific IgE antibodies. The Korean Inhalant Panel test on 20 patients and Food Panel test on 19 patients were performed using the conventional manual MAST-CLA kit and the new automated MAST-CLA method (automated AP720S system for the Optigen Assay; Hitachi Chemical Diagnostics, Inc., USA) simultaneously. The results were evaluated for positive reactivity and concordance. The results of inhalant panel gave a relatively higher class level result than the food panel. The 8 patients out of 20 (40%) of the inhalation panel, and 9 patients out of 18 (47.4%) of the food panel showed 100% concordance between the 2 systems. Eighteen patients (90%) of the Inhalation Panel and sixteen patients (84.2%) of the Food Panel showed more than 91% concordance. These results suggest that the MAST-CLA assay using the new, automated AP720S analyzer performs well, showing a high concordance rate with conventional MAST-CLA. Compared to manual MAST-CLA, the automated AP720S system has a shorter assay time and uses a smaller serum volume (500 microl) along with other conveniences.

Two centuries of masting data for European beech and Norway spruce across the European continent.

PubMed

Ascoli, Davide; Maringer, Janet; Hacket-Pain, Andy; Conedera, Marco; Drobyshev, Igor; Motta, Renzo; Cirolli, Mara; Kantorowicz, Władysław; Zang, Christian; Schueler, Silvio; Croisé, Luc; Piussi, Pietro; Berretti, Roberta; Palaghianu, Ciprian; Westergren, Marjana; Lageard, Jonathan G A; Burkart, Anton; Gehrig Bichsel, Regula; Thomas, Peter A; Beudert, Burkhard; Övergaard, Rolf; Vacchiano, Giorgio

2017-05-01

Tree masting is one of the most intensively studied ecological processes. It affects nutrient fluxes of trees, regeneration dynamics in forests, animal population densities, and ultimately influences ecosystem services. Despite a large volume of research focused on masting, its evolutionary ecology, spatial and temporal variability, and environmental drivers are still matter of debate. Understanding the proximate and ultimate causes of masting at broad spatial and temporal scales will enable us to predict tree reproductive strategies and their response to changing environment. Here we provide broad spatial (distribution range-wide) and temporal (century) masting data for the two main masting tree species in Europe, European beech (Fagus sylvatica L.) and Norway spruce (Picea abies (L.) H. Karst.). We collected masting data from a total of 359 sources through an extensive literature review and from unpublished surveys. The data set has a total of 1,747 series and 18,348 yearly observations from 28 countries and covering a time span of years 1677-2016 and 1791-2016 for beech and spruce, respectively. For each record, the following information is available: identification code; species; year of observation; proxy of masting (flower, pollen, fruit, seed, dendrochronological reconstructions); statistical data type (ordinal, continuous); data value; unit of measurement (only in case of continuous data); geographical location (country, Nomenclature of Units for Territorial Statistics NUTS-1 level, municipality, coordinates); first and last record year and related length; type of data source (field survey, peer reviewed scientific literature, gray literature, personal observation); source identification code; date when data were added to the database; comments. To provide a ready-to-use masting index we harmonized ordinal data into five classes. Furthermore, we computed an additional field where continuous series with length >4 yr where converted into a five classes ordinal index. To our knowledge, this is the most comprehensive published database on species-specific masting behavior. It is useful to study spatial and temporal patterns of masting and its proximate and ultimate causes, to refine studies based on tree-ring chronologies, to understand dynamics of animal species and pests vectored by these animals affecting human health, and it may serve as calibration-validation data for dynamic forest models. © 2017 by the Ecological Society of America.

Evaluation of mast cells, eosinophils, blood capillaries in oral lichen planus and oral lichenoid mucositis.

PubMed

Reddy, D Santhosh; Sivapathasundharam, B; Saraswathi, T R; SriRam, G

2012-01-01

Mast cells are granule containing secretory cells present in oral mucosal and connective tissue environment. Oral lichen planus and oral lichenoid lesions are commonly occurring oral diseases and have some similarity clinically and histologically. Both are characterized by an extensive sub epithelial infiltrate of T cells, together with mast cells, eosinophils and blood capillaries. In this study mast cell and eosinophil densities along with number of blood capillaries were studied to find out if they could aid in histopathological distinction between oral lichen planus and lichenoid mucositis. To enumerate mast cells and compare the status of Mast Cells (Intact or Degranulated) in Lichen planus, Lichenoid mucositis and normal buccal mucosa in tissue sections stained with Toluidine Blue, and also to enumerate Eosinophils and blood capillaries in tissue sections stained with H and E. The study group included 30 cases each of oral lichen planus and oral lichenoid mucositis. 10 cases of clinically normal oral buccal mucosa formed the control group. All the sections were stained with Toluidine blue and H and E separately. Histopathological analysis was done using binocular light microscope equipped with square ocular grid to standardize the field of evaluation. The result of the study showed. · Significant increase in number of mast cells in oral lichen planus and oral lichenoid mucositis compared to normal buccal mucosa. · Significant increase of intact mast cells suepithelially within the inflammatory cell infiltrate in oral lichen planus compared to oral lichenoid mucositis. · Significant increase of degranulated mast cells in oral lichenoid mucositis to oral lichen planus, and increase in number of eosinophil densities in oral lichenoid mucositis compared to oral lichen planus. · Significant increase in number of capillaries in oral lichenoid mucositis compared to oral lichen planus. The findings of increased number of intact mast cells sub epithelially in oral lichen planus to oral lichenoid mucositis and increase in number of degranulated mast cells as well as capillaries subepithelially in oral lichenoid mucositis to oral lichen planus can be used as reliable criteria for histologic distinction between these two lesions. The increase of eosinophils in oral lichenoid mucositis to oral lichen planus could be used as adjunct histologic criterion in the diagnosis of oral lichenoid mucositis.

Characterization of various types of mast cells derived from model mice of familial gastrointestinal stromal tumors with KIT-Asp818Tyr mutation

PubMed Central

Kajimoto, Noriko; Nakai, Norihiro; Ohkouchi, Mizuka; Hashikura, Yuka; Liu-Kimura, Ning-Ning; Isozaki, Koji; Hirota, Seiichi

2015-01-01

Sporadic mast cell neoplasms and gastrointestinal stromal tumors (GISTs) often have various types of somatic gain-of-function mutations of the c-kit gene which encodes a receptor tyrosine kinase, KIT. Several types of germline gain-of-function mutations of the c-kit gene have been detected in families with multiple GISTs. All three types of model mice for the familial GISTs with germline c-kit gene mutations at exon 11, 13 or 17 show development of GIST, while they are different from each other in skin mast cell number. Skin mast cell number in the model mice with exon 17 mutation was unchanged compared to the corresponding wild-type mice. In the present study, we characterized various types of mast cells derived from the model mice with exon 17 mutation (KIT-Asp818Tyr) corresponding to human familial GIST case with human KIT-Asp820Tyr to clarify the role of the c-kit gene mutation in mast cells. Bone marrow-derived cultured mast cells (BMMCs) derived from wild-type mice, heterozygotes and homozygotes were used for the experiments. Immortalized BMMCs, designated as IMC-G4 cells, derived from BMMCs of a homozygote during long-term culture were also used. Ultrastructure, histamine contents, proliferation profiles and phosphorylation of various signaling molecules in those cells were examined. In IMC-G4 cells, presence of additional mutation(s) of the c-kit gene and effect of KIT inhibitors on both KIT autophosphorylation and cell proliferation were also analyzed. We demonstrated that KIT-Asp818Tyr did not affect ultrastructure and proliferation profiles but did histamine contents in BMMCs. IMC-G4 cells had an additional novel c-kit gene mutation of KIT-Tyr421Cys which is considered to induce neoplastic transformation of mouse mast cells and the mutation appeared to be resistant to a KIT inhibitor of imatinib but sensitive to another KIT inhibitor of nilotinib. IMC-G4 cells might be a useful mast cell line to investigate mast cell biology. PMID:26722383

Clinical Features of Hereditary and Mast Cell-mediated Angioedema Focusing on the Differential Diagnosis in Japanese Patients.

PubMed

Ohsawa, Isao; Honda, Daisuke; Hisada, Atsuko; Inoshita, Hiroyuki; Onda-Tsueshita, Kisara; Mano, Satoshi; Sato, Nobuyuki; Nakamura, Yuya; Shimizu, Tatsuo; Gotoh, Hiromichi; Goto, Yoshikazu; Suzuki, Yusuke; Tomino, Yasuhiko

2018-02-01

Objective The present study was designed to identify the clinical characteristics that permit the differential diagnosis of hereditary angioedema (HAE) and mast cell-mediated angioedema (Mast-AE) during the first consultation. Methods The medical histories and laboratory data of 46 patients with HAE and 41 patients with Mast-AE were compared. Results The average age of onset in the HAE group (19.8±9.0 years) was significantly lower than that in the Mast-AE group (35.2±12.0 years). The incidence of familial angioedema (AE) in the HAE group (73.9%) was significantly higher than that in the Mast-AE group (9.7%). The frequency of history of AE in the extremities, larynx, or gastrointestinal tract was significantly higher in the HAE group. The frequency of AE episodes of the lips and eyelids was significantly lower in the HAE group. The serum C4 concentration and CH50 titer were lower than the normal limit in 91.3% and 45.6% of the patients in the HAE group, respectively; in Mast-AE group the serum C4 concentration and CH50 titer were significantly lower than the normal limit in 4.8% and 0% of the patients, the difference between the two groups was statistically significant. A C1-inhibitor (C1-INH) activity level of <50% was observed in all of the HAE patients, but none of the Mast-AE patients. The mean serum IgE titer in the HAE group (120.8±130.5 IU/mL) was significantly lower than that in the Mast-AE group (262.2±314.9 IU/mL). Conclusion The parameters within the patients' medical histories, such as the age at the onset of AE, a family history of AE, and the locations of past AE episodes are critical for the successful diagnosis of the disease. Measurements of the C4 and C1-INH activity are very useful for differential diagnosis of HAE from Mast-AE.

Bait stations, hard mast, and black bear population growth in Great Smoky Mountains National Park

USGS Publications Warehouse

Clark, Joseph D.; van Manen, Frank T.; Pelton, Michael R.

2005-01-01

Bait-station surveys are used by wildlife managers as an index to American black bear (Ursus americanus) population abundance, but the relationship is not well established. Hard mast surveys are similarly used to assess annual black bear food availability which may affect mortality and natality rates. We used data collected in Great Smoky Mountains National Park (GSMNP) from 1989 to 2003 to determine whether changes in the bait-station index (ΔBSI) were associated with estimated rates of bear population growth (λ) and whether hard mast production was related to bear visitation to baits. We also evaluated whether hard mast production from previous years was related to λ. Estimates of λ were based on analysis of capture-recapture data with the Pradel temporal symmetry estimator. Using the Akaike's Information Criterion (AIC), our analysis revealed no direct relationship between ΔBSI and λ. A simulation analysis indicated that our data were adequate to detect a relationship had one existed. Model fit was marginally improved when we added total oak mast production of the previous year as an interaction term suggesting that the BSI was confounded with environmental variables. Consequently the utility of the bait-station survey as a population monitoring technique is questionable at the spatial and temporal scales we studied. Mast survey data, however, were valuable covariates of λ. Population growth for a given year was negatively related to oak mast production 4 and 5 years prior. That finding supported our hypothesis that mast failures can trigger reproductive synchrony, which may not be evident from the trapped sample until years later.

Ascomycin macrolactam derivative SDZ ASM 981 inhibits the release of granule-associated mediators and of newly synthesized cytokines in RBL 2H3 mast cells in an immunophilin-dependent manner.

PubMed

Hultsch, T; Müller, K D; Meingassner, J G; Grassberger, M; Schopf, R E; Knop, J

1998-09-01

Mast cells play an important role in the pathological development of many inflammatory and allergic diseases and inhibition of mast cell activation is a potential target for therapeutic intervention. Therefore, the effect of the novel ascomycin macrolactam derivative SDZ ASM 981 on Fc epsilonRI-mediated activation of rat basophilic leukemia (RBL) cells, as a model for mast cell activation, was investigated. First, the ability to inhibit different mast cell immunophilins in vitro was tested. Using recombinant macrophilin-12 (FKBP-12), inhibition of rotamase activity with an IC50 of approximately 6 nM was observed. The rotamase activity of cyclophilin A (18 kDa) was not affected. Secondly, the effect of SDZ ASM 981 on Fc epsilonRI-mediated mast cell activation was investigated in the RBL cell model. SDZ ASM 981 inhibited exocytosis of preformed mediators (e.g. serotonin) with an IC50 of approximately 30 nM. Transcription and release of newly synthesized mediators (e.g. TNF-alpha) was inhibited with an IC50 of approximately 100 nM. The inhibitory effect of SDZ ASM 981 was antagonized by rapamycin. We conclude that SDZ ASM 981 is a potent inhibitor of Fc epsilonRI-mediated activation of mast cells in vitro. The mechanism of action involves formation of (calcineurin) inhibitory complexes with macrophilins. We suggest that this inhibitory action on mast cells might contribute to the antiinflammatory effect of SDZ ASM 981 observed in vivo (e.g. in aptopic dermatitis and psoriasis).

Generation of Mast Cells from Mouse Fetus: Analysis of Differentiation and Functionality, and Transcriptome Profiling Using Next Generation Sequencer

PubMed Central

Fukuishi, Nobuyuki; Igawa, Yuusuke; Kunimi, Tomoyo; Hamano, Hirofumi; Toyota, Masao; Takahashi, Hironobu; Kenmoku, Hiromichi; Yagi, Yasuyuki; Matsui, Nobuaki; Akagi, Masaaki

2013-01-01

While gene knockout technology can reveal the roles of proteins in cellular functions, including in mast cells, fetal death due to gene manipulation frequently interrupts experimental analysis. We generated mast cells from mouse fetal liver (FLMC), and compared the fundamental functions of FLMC with those of bone marrow-derived mouse mast cells (BMMC). Under electron microscopy, numerous small and electron-dense granules were observed in FLMC. In FLMC, the expression levels of a subunit of the FcεRI receptor and degranulation by IgE cross-linking were comparable with BMMC. By flow cytometry we observed surface expression of c-Kit prior to that of FcεRI on FLMC, although on BMMC the expression of c-Kit came after FcεRI. The surface expression levels of Sca-1 and c-Kit, a marker of putative mast cell precursors, were slightly different between bone marrow cells and fetal liver cells, suggesting that differentiation stage or cell type are not necessarily equivalent between both lineages. Moreover, this indicates that phenotypically similar mast cells may not have undergone an identical process of differentiation. By comprehensive analysis using the next generation sequencer, the same frequency of gene expression was observed for 98.6% of all transcripts in both cell types. These results indicate that FLMC could represent a new and useful tool for exploring mast cell differentiation, and may help to elucidate the roles of individual proteins in the function of mast cells where gene manipulation can induce embryonic lethality in the mid to late stages of pregnancy. PMID:23573287

Comparison of Mast Cells Count in Odontogenic Cysts Using Histochemical Staining

PubMed Central

Rajabi-Moghaddam, Mahdieh; Abbaszadeh-Bidokhty, Hamid; Bijani, Ali

2015-01-01

Background & Objectives: Odontogenic cysts are among the most frequent destructive lesions of jaws which their pathogenesis and growth mechanism are not cleared. With respect to different roles of mast cells, they may play a role in the pathogenesis and growth of odontogenic cysts. The aim of present study was to evaluate mast cells in the most common odontogenic cyst. Methods: Thirty paraffin-embedded tissue blocks including 10 radicular cysts, 10 dentigerous cysts and 10 odontogenic keratocysts were used and 5 micron sections stained with toluidine blue and observed by light microscope under ×400 magnification to evaluate mast cells within these cysts. For each case, 5 high-power field areas, selected from hot-spot areas, were considered and each area divided into 3 zones: intra-epithelial zone, sub-epithelial zone and deep zone. Results: Most of the studied cyst showed presence of mast cells. There was not any significant difference in mast cell count between studied cysts ( P -values > 0.05).With respect to intra-epithelial, sub-epithelial and deep zones, there was not any significant difference between three studied cysts. There was not any significant difference between sub-epithelial zone and deep zone within each of these cysts. There was only significant difference between intra-epithelial zone and sub-epithelial zone within dentigerous cysts and odontogenic keratocysts ( P -value < 0.05). Conclusions: Prevalence of mast cells in fibrous wall of odontogenic cysts suggests their activity in these cysts. Mast cells may not be directly involved in the pathogenesis of odontogenic keratocysts. PMID:26351470

Mast cells and their mediators in cutaneous wound healing--active participants or innocent bystanders?

PubMed

Artuc, M; Hermes, B; Steckelings, U M; Grützkau, A; Henz, B M

1999-02-01

Mast cells are traditionally viewed as effector cells of immediate type hypersensitivity reactions. There is, however, a growing body of evidence that the cells might play an important role in the maintenance of tissue homeostasis and repair. We here present our own data and those from the literature elucidating the possible role of mast cells during wound healing. Studies on the fate of mast cells in scars of varying ages suggest that these cells degranulate during wounding, with a marked decrease of chymase-positive cells, although the total number of cells does not decrease, based on SCF-receptor staining. Mast cells contain a plethora of preformed mediators like heparin, histamine, tryptase, chymase, VEGF and TNF-alpha which, on release during the initial stages of wound healing, affect bleeding and subsequent coagulation and acute inflammation. Various additional vasoactive and chemotactic, rapidly generated mediators (C3a, C5a, LTB4, LTC4, PAF) will contribute to these processes, whereas mast cell-derived proinflammatory and growth promoting peptide mediators (VEGF, FGF-2, PDGF, TGF-beta, NGF, IL-4, IL-8) contribute to neoangiogenesis, fibrinogenesis or re-epithelization during the repair process. The increasing number of tryptase-positive mast cells in older scars suggest that these cells continue to be exposed to specific chemotactic, growth- and differentiation-promoting factors throughout the process of tissue remodelling. All these data indicate that mast cells contribute in a major way to wound healing. their role as potential initiators of or as contributors to this process, compared to other cell types, will however have to be further elucidated.

Spontaneous locomotor activity correlates with the degranulation of mast cells in the meninges rather than in the thalamus: Disruptive effect of cocaine

PubMed Central

Larson, Alice A.; Thomas, Mark J.; McElhose, Alex; Kovács, Katalin J.

2011-01-01

Mast cells are located in the central nervous system (CNS) of many mammals and stress induces their degranulation. We postulated that mast cells are associated with wakefulness and stimulatory tone in the CNS, as reflected by spontaneous motor activity. Because stress also precipitates drug-seeking behavior in cocaine addicts, we also postulated that cocaine manifests its effects through this relationship. We investigated the influence of single and repeated injections of cocaine on circulating corticosterone, motor activity and degranulation of mast cells in both the thalamus and meninges of mice. Mice were subjected to 5 consecutive days of cocaine or saline followed by a single injection of cocaine or saline 11 days later. Spontaneous locomotor activity was measure for one hour after the final injection before death. Neither a single injection nor prior treatment with cocaine increased motor activity compared to saline-injected controls, however, repeated administration of cocaine induced a significant sensitization to its behavioral effect when delivered 11 days later. In mice that received only saline, motor activity correlated positively with mast cell degranulation in the meninges but not in the thalamus. Cocaine, regardless of the treatment schedule, disrupted this correlation. The concentration of corticosterone did not differ amongst groups and did not correlate with either behavior or mast cell parameters in any group. The correlation between behavioral activity and the mast cell degranulation in the meninges suggests that these parameters are linked. The disruptive effect of cocaine on this relationship indicates a role downstream from mast cells in the regulation of motor activity. PMID:21561602

Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE.

PubMed

Christy, Alison L; Walker, Margaret E; Hessner, Martin J; Brown, Melissa A

2013-05-01

The meninges are often considered inert tissues that house the CSF and provide protection for the brain and spinal cord. Yet emerging data demonstrates that they are also active sites of immune responses. Furthermore, the blood-CSF barrier surrounding meningeal blood vessels, together with the blood-brain barrier (BBB), is postulated to serve as a gateway for the pathological infiltration of immune cells into the CNS in multiple sclerosis (MS). Our previous studies using mast cell-deficient (Kit(W/Wv)) mice demonstrated that mast cells resident in the dura mater and pia mater exacerbate experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, by facilitating CNS inflammatory cell influx. Here we examined the underlying mechanisms that mediate these effects. We demonstrate that there are dramatic alterations in immune associated gene expression in the meninges in pre-clinical disease, including those associated with mast cell and neutrophil function. Meningeal mast cells are activated within 24 h of disease induction, but do not directly compromise CNS vascular integrity. Rather, through production of TNF, mast cells elicit an early influx of neutrophils, cells known to alter vascular permeability, into the meninges. These data add to the growing evidence that inflammation in the meninges precedes CNS immune cell infiltration and establish that mast cells are among the earliest participants in these disease-initiating events. We hypothesize that mast cell-dependent neutrophil recruitment and activation in the meninges promotes early breakdown of the local BBB and CSF-blood barrier allowing initial immune cell access to the CNS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Recombinant ArtinM activates mast cells.

PubMed

Barbosa-Lorenzi, Valéria Cintra; Cecilio, Nerry Tatiana; de Almeida Buranello, Patricia Andressa; Pranchevicius, Maria Cristina; Goldman, Maria Helena S; Pereira-da-Silva, Gabriela; Roque-Barreira, Maria Cristina; Jamur, Maria Célia; Oliver, Constance

2016-07-04

Mast cells are hematopoietically derived cells that play a role in inflammatory processes such as allergy, as well as in the immune response against pathogens by the selective and rapid release of preformed and lipid mediators, and the delayed release of cytokines. The native homotetrameric lectin ArtinM, a D-mannose binding lectin purified from Artocarpus heterophyllus seeds, is one of several lectins that are able to activate mast cells. Besides activating mast cells, ArtinM has been shown to affect several biological responses, including immunomodulation and acceleration of wound healing. Because of the potential pharmacological application of ArtinM, a recombinant ArtinM (rArtinM) was produced in Escherichia coli. The current study evaluated the ability of rArtinM to induce mast cell degranulation and activation. The glycan binding specificity of rArtinM was similar to that of jArtinM. rArtinM, via its CRD, was able to degranulate, releasing β-hexosaminidase and TNF-α, and to promote morphological changes on the mast cell surface. Moreover, rArtinM induced the release of the newly-synthesized mediator, IL-4. rArtinM does not have a co-stimulatory effect on the FcεRI degranulation via. The IgE-dependent mast cell activation triggered by rArtinM seems to be dependent on NFkB activation. The lectin rArtinM has the ability to activate and degranulate mast cells via their CRDs. The present study indicates that rArtinM is a suitable substitute for the native form, jArtinM, and that rArtinM may serve as an important and reliable pharmacological agent.

Sulfur mustard induced mast cell degranulation in mouse skin is inhibited by a novel anti-inflammatory and anticholinergic bifunctional prodrug.

PubMed

Joseph, Laurie B; Composto, Gabriella M; Perez, Roberto M; Kim, Hong-Duck; Casillas, Robert P; Heindel, Ned D; Young, Sherri C; Lacey, Carl J; Saxena, Jaya; Guillon, Christophe D; Croutch, Claire R; Laskin, Jeffrey D; Heck, Diane E

2018-09-01

Sulfur mustard (SM, bis(2-chloroethyl sulfide) is a potent vesicating agent known to cause skin inflammation, necrosis and blistering. Evidence suggests that inflammatory cells and mediators that they generate are important in the pathogenic responses to SM. In the present studies we investigated the role of mast cells in SM-induced skin injury using a murine vapor cup exposure model. Mast cells, identified by toluidine blue staining, were localized in the dermis, adjacent to dermal appendages and at the dermal/epidermal junction. In control mice, 48-61% of mast cells were degranulated. SM exposure (1.4g/m 3 in air for 6min) resulted in increased numbers of degranulated mast cells 1-14days post-exposure. Treatment of mice topically with an indomethacin choline bioisostere containing prodrug linked by an aromatic ester-carbonate that targets cyclooxygenases (COX) enzymes and acetylcholinesterase (1% in an ointment) 1-14days after SM reduced skin inflammation and injury and enhanced tissue repair. This was associated with a decrease in mast cell degranulation from 90% to 49% 1-3days post SM, and from 84% to 44% 7-14days post SM. These data suggest that reduced inflammation and injury in response to the bifunctional indomethacin prodrug may be due, at least in part, to abrogating mast cell degranulation. The use of inhibitors of mast cell degranulation may be an effective strategy for mitigating skin injury induced by SM. Copyright © 2017 Elsevier B.V. All rights reserved.

BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.

PubMed

Min, Arim; Lee, Young Ah; Kim, Kyeong Ah; Shin, Myeong Heon

2018-05-31

Trichomonas vaginalis is a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis. Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited. O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP). Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861 inhibited migration of mast cells. This result suggested that mast cell migration was caused by stimulation of T. vaginalis-secreted leukotrienes. Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB 4 receptor (BLT1). Furthermore, TvSP induced protein O-GlcNAcylation and OGT expression in HMC-1 cells, which was prevented by transfection with BLT1 siRNA. TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatmemnt with OGT inhibitor ST045849 or OGT siRNA. These results suggested that BLT1-mediated OGlcNAcylation was important for mast cell activation during trichomoniasis. Copyright © 2018. Published by Elsevier Masson SAS.

Inhibitory effects of low molecular weight heparin on mediator release by mast cells: preferential inhibition of cytokine production and mast cell-dependent cutaneous inflammation

PubMed Central

BARAM, D; RASHKOVSKY, M; HERSHKOVIZ, R; DRUCKER, I; RESHEF, T; BEN-SHITRIT, S; MEKORI, Y A

1997-01-01

There has been substantial evidence that suggests that heparin may modulate various aspects of immune function and inflammation in addition to its well known anticoagulant activity. In this regard heparin was found to suppress cell-mediated immune responses or asthmatic reactions to allergen challenge. In the present study we analyse the effects of low molecular weight heparin (LMWH) on mast cell degranulation and cytokine production in vitro and on the elicitation of IgE-mediated mast cell-dependent late cutaneous allergic inflammation in vivo. We have established that LMWH preferentially inhibited tumour necrosis factor-alpha (TNF-α) and IL-4 production without having any significant effect on mast cell degranulation. These effects have been observed in mast cells derived from three different origins that were activated by either immunological or non-immunological stimuli. We have shown that there is inhibition of TNF-α production (and not neutralization of activity), as elimination of the drug after a short preincubation and addition of LMWH to rTNF-α had no effect on TNF-α-mediated cytotoxic activity. These results were also confirmed by ELISA. In vivo, s.c. injection of the LMWH inhibited the leucocyte infiltration associated with the late cutaneous response which followed passive cutaneous anaphylaxis (PCA) reaction, without affecting mast cell numbers or degranulation. These data suggest that LMWH may have an inhibitory role in mast cell-mediated allergic inflammation, and thus might be considered as a possible therapeutic modality. PMID:9409655

The Relationship Between Basal Area and Hard Mast Production in the Ouachita Mountains

Treesearch

Roger W. Perry; Ronald E. Thill; Philip A. Tappe; David G. Peitz

2004-01-01

Abstract - Because the relationship between stand density and hard mast production is not clear, we investigated the effects of varying total overstory basal area (BA) on acorn and hickory nut production in the Ouachita Mountains. We used Whitehead visual surveys to estimate mast production in oaks (Quercus spp.) and hickories (...

Expression of Tocopherol-Associated Protein in Mast Cells

PubMed Central

Ikeda, Teruo; Murakami, Masaru; Funaba, Masayuki

2004-01-01

Tocopherol-associated protein (TAP) was expressed in mouse mast cells. TAP was predominantly localized in the cytoplasm, and the subcellular localization was not changed by α-tocopherol. The results suggest that the physiological role of TAP in mast cells is not regulation of tocopherol function but an as-yet-unidentified activity. PMID:15539527

MAST

Science.gov Websites

Guide Related Sites submenu NASA Datacenters ADS HEASARC IRSA LAMBDA NED NSSDC MAST Services submenu Archive for Space Telescopes (MAST) is a NASA funded project to support and provide to the astronomical : STScI may provide links to Web pages that are not part of the STScI, AURA, NASA, or ESA domain. These

Malignant mast cell tumor in an African hedgehog (Atelerix albiventris).

PubMed

Raymond, J T; White, M R; Janovitz, E B

1997-01-01

In November 1995, a malignant mast cell tumor (mastocytoma) was diagnosed in an adult African hedgehog (Atelerix albiventris) from a zoological park (West Lafayette, Indiana, USA). The primary mast cell tumor presented as a firm subcutaneous mass along the ventrum of the neck. Metastasis to the right submandibular lymph node occurred.

Reciprocal regulation of ARPP-16 by PKA and MAST3 kinases provides a cAMP-regulated switch in protein phosphatase 2A inhibition.

PubMed

Musante, Veronica; Li, Lu; Kanyo, Jean; Lam, Tukiet T; Colangelo, Christopher M; Cheng, Shuk Kei; Brody, A Harrison; Greengard, Paul; Le Novère, Nicolas; Nairn, Angus C

2017-06-14

ARPP-16, ARPP-19, and ENSA are inhibitors of protein phosphatase PP2A. ARPP-19 and ENSA phosphorylated by Greatwall kinase inhibit PP2A during mitosis. ARPP-16 is expressed in striatal neurons where basal phosphorylation by MAST3 kinase inhibits PP2A and regulates key components of striatal signaling. The ARPP-16/19 proteins were discovered as substrates for PKA, but the function of PKA phosphorylation is unknown. We find that phosphorylation by PKA or MAST3 mutually suppresses the ability of the other kinase to act on ARPP-16. Phosphorylation by PKA also acts to prevent inhibition of PP2A by ARPP-16 phosphorylated by MAST3. Moreover, PKA phosphorylates MAST3 at multiple sites resulting in its inhibition. Mathematical modeling highlights the role of these three regulatory interactions to create a switch-like response to cAMP. Together, the results suggest a complex antagonistic interplay between the control of ARPP-16 by MAST3 and PKA that creates a mechanism whereby cAMP mediates PP2A disinhibition.

A Role for Serglycin Proteoglycan in Mast Cell Apoptosis Induced by a Secretory Granule-mediated Pathway*

PubMed Central

Melo, Fabio Rabelo; Waern, Ida; Rönnberg, Elin; Åbrink, Magnus; Lee, David M.; Schlenner, Susan M.; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Turk, Boris; Wernersson, Sara; Pejler, Gunnar

2011-01-01

Mast cell secretory granules (secretory lysosomes) contain large amounts of fully active proteases bound to serglycin proteoglycan. Damage to the granule membrane will thus lead to the release of serglycin and serglycin-bound proteases into the cytosol, which potentially could lead to proteolytic activation of cytosolic pro-apoptotic compounds. We therefore hypothesized that mast cells are susceptible to apoptosis induced by permeabilization of the granule membrane and that this process is serglycin-dependent. Indeed, we show that wild-type mast cells are highly sensitive to apoptosis induced by granule permeabilization, whereas serglycin-deficient cells are largely resistant. The reduced sensitivity of serglycin−/− cells to apoptosis was accompanied by reduced granule damage, reduced release of proteases into the cytosol, and defective caspase-3 activation. Mechanistically, the apoptosis-promoting effect of serglycin involved serglycin-dependent proteases, as indicated by reduced sensitivity to apoptosis and reduced caspase-3 activation in cells lacking individual mast cell-specific proteases. Together, these findings implicate serglycin proteoglycan as a novel player in mast cell apoptosis. PMID:21123167

Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis

PubMed Central

Piliponsky, Adrian M.; Chen, Ching-Cheng; Nishimura, Toshihiko; Metz, Martin; Rios, Eon J.; Dobner, Paul R.; Wada, Etsuko; Wada, Keiji; Zacharias, Sherma; Mohanasundaram, Uma; Faix, James D.; Abrink, Magnus; Pejler, Gunnar; Pearl, Ronald; Tsai, Mindy; Galli, Stephen J.

2010-01-01

Sepsis is a complex, incompletely understood and often fatal disorder,1 typically accompanied by hypotension,2 that is considered to represent a dysregulated host response to infection.3,4,5 Neurotensin (NT) is a 13-amino-acid peptide that, among its multiple effects, induces hypotension.6 We find that intraperitoneal and plasma concentrations of NT are increased in mice after severe caecal ligation and puncture (CLP), a model of sepsis, and that mice treated with a pharmacological antagonist of NT, or NT-deficient mice, exhibit reduced mortality during severe CLP. In mice, mast cells can degrade NT and reduce NT-induced hypotension and CLP-associated mortality, and optimal expression of these effects requires mast cell expression of neurotensin receptor 1 and neurolysin. These findings show that NT contributes to sepsis-related mortality in mice during severe CLP and that mast cells can lower NT concentrations, and suggest that mast cell-dependent reduction in NT levels contributes to the ability of mast cells to enhance survival after CLP. PMID:18376408

Effect of methylmercury on the rat mast cell degranulation

NASA Astrophysics Data System (ADS)

Graevskaya, E. E.; Yasutake, A.; Aramai, R.; Rubin, A. B.

2003-05-01

Methylmercury is the well-known neurotoxicant as weil as a modulator of the immune system. We investigated the effects of MeHg on the rat mast cell degranulation induced by nonimmunological stimuli (the selective liberator of histamine, compound 48/80, and calcium ionophore A23187) both in vivo and in vitro. In 8, 12 and 15 days afterthe final administration of MeHg we observed the suppression of calcium ionophore A23187-and 48/80-induced histamine release, which enhanced with time. In experiments in vitro incubation of peritoneal mast cells with MeHg alone in the dose range 10^{-8} to 10^{-6} did not induce mast cell degranulation, however modified the activation of mast cells by compound 48/80, and calcium ionophore A23187. We observed activation of stimulated secretion by preliminary incubation with low dose of MeHg 10^{-8} M and inhibition by dose of MeHg 10^{-6} M. These results show that MeHg treatment can modify mast cell function in vivo and in vitro and provide insight into the understanding what role this cell has in the pathogenesis of Minamata disease-comlected disorders.

(E,Z)-3-(3',5'-Dimethoxy-4'-hydroxy-benzylidene)-2-indolinone blocks mast cell degranulation.

PubMed

Kiefer, S; Mertz, A C; Koryakina, A; Hamburger, M; Küenzi, P

2010-05-12

(E,Z)-3-(3',5'-Dimethoxy-4'-hydroxy-benzylidene)-2-indolinone (indolinone) is an alkaloid that has been identified as a pharmacologically active compound in extracts of the traditional anti-inflammatory herb Isatis tinctoria. Indolinone has been shown to inhibit compound 48/80-induced mast cell degranulation in vitro. Application of indolinone to bone marrow derived mast cells showed that it was uniformly distributed in the cytoplasm and that cellular uptake was terminated within minutes. Pre-treatment of IgE-sensitized mast cells with 100nM indolinone rendered them insensitive against FcvarepsilonRI-receptor dependent degranulation. However, upstream signalling induced by antigen such as activation of PI3-K and MAPK remained unaffected. We conclude that indolinone blocks mast cell degranulation at the level of granule exocitosis with an IC(50) of 54nm.

Beyond apoptosis: the mechanism and function of phosphatidylserine asymmetry in the membrane of activating mast cells.

PubMed

Rysavy, Noel M; Shimoda, Lori M N; Dixon, Alyssa M; Speck, Mark; Stokes, Alexander J; Turner, Helen; Umemoto, Eric Y

2014-01-01

Loss of plasma membrane asymmetry is a hallmark of apoptosis, but lipid bilayer asymmetry and loss of asymmetry can contribute to numerous cellular functions and responses that are independent of programmed cell death. Exofacial exposure of phosphatidylserine occurs in lymphocytes and mast cells after antigenic stimulation and in the absence of apoptosis, suggesting that there is a functional requirement for phosphatidylserine exposure in immunocytes. In this review we examine current ideas as to the nature of this functional role in mast cell activation. Mechanistically, there is controversy as to the candidate proteins responsible for phosphatidylserine translocation from the internal to external leaflet, and here we review the candidacies of mast cell PLSCR1 and TMEM16F. Finally we examine the potential relationship between functionally important mast cell membrane perturbations and phosphatidylserine exposure during activation.

LiDAR error estimation with WAsP engineering

NASA Astrophysics Data System (ADS)

Bingöl, F.; Mann, J.; Foussekis, D.

2008-05-01

The LiDAR measurements, vertical wind profile in any height between 10 to 150m, are based on assumption that the measured wind is a product of a homogenous wind. In reality there are many factors affecting the wind on each measurement point which the terrain plays the main role. To model LiDAR measurements and predict possible error in different wind directions for a certain terrain we have analyzed two experiment data sets from Greece. In both sites LiDAR and met, mast data have been collected and the same conditions are simulated with RisØ/DTU software, WAsP Engineering 2.0. Finally measurement data is compared with the model results. The model results are acceptable and very close for one site while the more complex one is returning higher errors at higher positions and in some wind directions.

Fatigue Resistant Design Criteria for MD SHA Cantilevered Mast Arm Signal Structure : Research Summary

DOT National Transportation Integrated Search

2017-12-01

Over the past two decades, wind induced fatigue cracking of highway signs, luminaires, and traffic signal support structures have been increasingly reported all over the United States. While fatalities associated with these failures have been limited...

Defective bone repair in mast cell-deficient Cpa3Cre/+ mice.

PubMed

Ramirez-GarciaLuna, Jose Luis; Chan, Daniel; Samberg, Robert; Abou-Rjeili, Mira; Wong, Timothy H; Li, Ailian; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Henderson, Janet E; Martineau, Paul A

2017-01-01

In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT) and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1) mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2) re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3) the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair.

Defective bone repair in mast cell-deficient Cpa3Cre/+ mice

PubMed Central

Chan, Daniel; Samberg, Robert; Abou-Rjeili, Mira; Wong, Timothy H.; Li, Ailian; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Henderson, Janet E.; Martineau, Paul A.

2017-01-01

In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT) and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1) mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2) re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3) the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair. PMID:28350850

Mast cell-dependent IL-33/ST2 signaling is protective against the development of airway hyperresponsiveness in a house dust mite mouse model of asthma.

PubMed

Zoltowska Nilsson, A M; Lei, Y; Adner, M; Nilsson, G P

2018-03-01

Interleukin-33 (IL-33) and its receptor ST2 have been influentially associated with the pathophysiology of asthma. Due to the divergent roles of IL-33 in regulating mast cell functions, there is a need to further characterize IL-33/ST2-dependent mast cell responses and their significance in the context of asthma. This study aimed to investigate how IL-33/ST2-dependent mast cell responses contribute to the development of airway hyperresponsiveness (AHR) and airway inflammation in a mouse model of house dust mite (HDM)-induced asthma. Mast cell-deficient C57BL/6-Kit W-sh (Wsh) mice engrafted with either wild-type (Wsh + MC-WT) or ST2-deficient bone marrow-derived mast cells (Wsh + MC-ST2KO) were exposed to HDM delivered intranasally. An exacerbated development of AHR in response to HDM was seen in Wsh + MC-ST2KO compared with Wsh + MC-WT mice. The contribution of this IL-33/ST2-dependent mast cell response to AHR seems to reside within the smaller airways in the peripheral parts of the lung, as suggested by the isolated yet marked effect on tissue resistance. Considering the absence of a parallel increase in cellular inflammation in bronchoalveolar lavage fluid (BALF) and lung, the aggravated AHR in Wsh + MC-ST2KO mice seems to be independent of cellular inflammation. We observed an association between the elevated AHR and reduced PGE 2 levels in BALF . Due to the protective properties of PGE 2 in airway responses, it is conceivable that IL-33/ST2-dependent mast cell induction of PGE 2 could be responsible for the dampening effect on AHR. In conclusion, we reveal that IL-33/ST2-dependent mast cell responses can have a protective, rather than causative role, in the development of AHR.

Changes in mast cells and in permeability of mesenteric microvessels under the effect of immobilization and electrostimulation

NASA Technical Reports Server (NTRS)

Gorizontova, M. P.

1980-01-01

It was shown that a reduction in the amount of mast cells in the mesentery and an increase in their degranulation was accompanied by an increase in vascular permeability of rat mesentery. It is supposed that immobilization and electrostimulation causing degranulation of mast cells prompted histamine and serotonin release from them, thus increasing the permeability of the venular portion of the microvascular bed. Prophylactic use of esculamin preparation with P-vitaminic activity decreased mast cell degranulation, which apparently prolonged the release of histamine and serotonin from them and normalized vascular permeability.

Identification of mast cells in buffy coat preparations from dogs with inflammatory skin diseases.

PubMed

Cayatte, S M; McManus, P M; Miller, W H; Scott, D W

1995-02-01

In 100 dogs with 4 inflammatory dermatologic diseases, buffy coat preparations from EDTA-treated blood samples were examined cytologically. Fifty-four dogs had atopy, 26 had flea-bite hypersensitivity, 17 had sarcoptic mange, and 3 had food allergy. Twenty-eight dogs had 2 or more concurrent skin diseases; most of these had secondary pyoderma. Dogs did not have mast cell tumors. Thirteen samples contained 1 or more mast cells/4 slides reviewed. This study revealed that dogs with inflammatory skin diseases can have a few to many mast cells evident on cytologic examination of buffy coat preparations.

Deployable and retractable telescoping tubular structure development

NASA Astrophysics Data System (ADS)

Thomson, M. W.

1993-02-01

The paper describes the design and the structural performance of a new type of deployable and retractable telescoping mast, which can be used for flight systems that require a deployable beam with superaccurate positioning characteristics or for short to medium highly loaded structural applications. The mast employs a Bi-STEM (a two-piece Storable Tubular Extendible Member) boom as an actuator and stabilizer, which alleviates the need for the deployed telescoping mast segments to overlap. Due to this feature and because the segments can be fully overlapped when stowed, the mast enables an unusually lightweight and compact launch configuration.

Idiopathic Mast Cell Activation Syndrome With Associated Salicylate Intolerance.

PubMed

Rechenauer, Tobias; Raithel, Martin; Götze, Thomas; Siebenlist, Gregor; Rückel, Aline; Baenkler, Hanns-Wolf; Hartmann, Arndt; Haller, Florian; Hoerning, André

2018-01-01

Idiopathic mast cell activation syndrome can be a rare cause for chronic abdominal pain in children. It remains a diagnosis by exclusion that can be particularly challenging due to the vast variety of possible clinical manifestations. We present a 13-year-old boy who suffered from a multitude of unspecific complaints over a long period of time. In this case, an assessment of mast cell-derived metabolites and immunohistochemical analysis of bioptic specimen was worthwhile. After ruling out, primary (oncologic) and secondary causes for mast cell activation, pharmacologic treatment adapted to the patient's salicylate intolerance resulted in a major relief of symptoms.

The Mast Cell, Contact, and Coagulation System Connection in Anaphylaxis

PubMed Central

Guilarte, Mar; Sala-Cunill, Anna; Luengo, Olga; Labrador-Horrillo, Moisés; Cardona, Victoria

2017-01-01

Anaphylaxis is the most severe form of allergic reaction, resulting from the effect of mediators and chemotactic substances released by activated cells. Mast cells and basophils are considered key players in IgE-mediated human anaphylaxis. Beyond IgE-mediated activation of mast cells/basophils, further mechanisms are involved in the occurrence of anaphylaxis. New insights into the potential relevance of pathways other than mast cell and basophil degranulation have been unraveled, such as the activation of the contact and the coagulation systems. Mast cell heparin released upon activation provides negatively charged surfaces for factor XII (FXII) binding and auto-activation. Activated FXII, the initiating serine protease in both the contact and the intrinsic coagulation system, activates factor XI and prekallikrein, respectively. FXII-mediated bradykinin (BK) formation has been proven in the human plasma of anaphylactic patients as well as in experimental models of anaphylaxis. Moreover, the severity of anaphylaxis is correlated with the increase in plasma heparin, BK formation and the intensity of contact system activation. FXII also activates plasminogen in the fibrinolysis system. Mast cell tryptase has been shown to participate in fibrinolysis through plasmin activation and by facilitating the degradation of fibrinogen. Some usual clinical manifestations in anaphylaxis, such as angioedema or hypotension, or other less common, such as metrorrhagia, may be explained by the direct effect of the activation of the coagulation and contact system driven by mast cell mediators. PMID:28798744

Role of Mast Cells in Oral Lichen Planus and Oral Lichenoid Reactions.

PubMed

Ramalingam, Suganya; Malathi, Narasimhan; Thamizhchelvan, Harikrishnan; Sangeetha, Narasimhan; Rajan, Sharada T

2018-01-01

Oral lichen planus (OLP) is a chronic T cell mediated disease of oral mucosa, skin, and its appendages with a prevalence of 0.5 to 2.6% worldwide. Oral lichenoid reactions (OLR) are a group of lesions with diverse aetiologies but have clinical and histological features similar to OLP, thereby posing a great challenge in differentiating both lesions. Mast cells are multifunctional immune cells that play a major role in the pathogenesis of lichen planus by release of certain chemical mediators. Increased mast cell densities with significant percentage of degranulation have been observed as a consistent finding in pathogenesis of oral lichen planus. The current study was aimed at quantifying the mast cells in histopathological sections of OLP and OLR thereby aiding a means of distinguishing these lesions. The study group involved 21 cases of oral lichen planus, 21 cases of oral lichenoid reactions, and 10 control specimens of normal buccal mucosa. All the cases were stained with Toluidine Blue and routine haematoxylin and eosin and the mast cells were quantified. The results were analyzed using the Kruskal-Wallis test and an intergroup analysis was performed using Mann-Whitney U test. The number of mast cells showed an increased value in oral lichen planus when compared to oral lichenoid reaction and thus an estimation of mast cells count could aid in distinguishing OLP from OLR histopathologically.

Mechanism of low-level laser therapy (LLLT) effects on rat mast cells

NASA Astrophysics Data System (ADS)

Popov, Gennady K.; Solovyova, Ludmila I.; Kosel, Arnold I.

2000-11-01

The low power laser radiation is widely applied for treatment of various diseases. In our research we investigated the influence of low power laser radiation on the mast cells degranulation process. The object of the research were the mesentery mast cells of the rat thin intestine. A loop of thin intestine was irradiated by the therapeutic diode laser device Uley - 2K (lambda - 890 nm, pulse). The process of mast cells degranulation served as a criterion for their functional activity estimation. The estimation was fulfilled with the help of light microscope (toluidine blue staining, pH02,0; degranulating mast cells counting on 100 cells; immersion technique; X 980). To study the dependence of degranulation process of mast cells irradiated with lasre from intracellular calcium (Ca2+) concentration we applied 0,000015 M solution of verapamil, which was applied to the mesentery for 2 minutes. Laser radiation (890 nm) stimulates mesentery mast cells degranulation. This effect is dose-dependent. Maximal degranulation was registered after laser irradiation wiht power 25 mW, exposure time 15-30 s (energy density 7.5 x 103 J/m2 to 6 x 104 j/m2). Further increasing of exposure time caused the effect decreasing. The results of our experiments with verpamil let us suppose light interaction with the voltage-dependent subunit of calcium channel, changing intracellular Ca2+ and leading to stimulatory effects.

Influence of laser and LED irradiation on mast cells of cutaneous wounds of rats with iron deficiency anemia

NASA Astrophysics Data System (ADS)

Becher Rosa, Cristiane; Oliveira Sampaio, Susana C. P.; Monteiro, Juliana S. C.; Ferreira, Maria F. L.; Zanini, Fátima A. A.; Santos, Jean N.; Cangussú, Maria Cristina T.; Pinheiro, Antonio L. B.

2011-03-01

This work aimed to study histologically the effect of Laser or LED phototherapy on mast cells on cutaneous wounds of rats with iron deficiency. 18 rats were used and fed with special peleted iron-free diet. An excisional wound was created on the dorsum of each animal which were divided into: Group I - Control with anemia + no treatment; Group II - Anemia + Laser; Group III - Anemia + LED; Group IV - Healthy + no treatment; Group V - Healthy + Laser; Group VI - Healthy + LED. Irradiation was performed using a diode Laser (λ660nm, 40mW, CW, total dose of 10J/cm2, 4X2.5J/cm2) or a RED-LED ( λ700nm, 15mW, CW, total dose of 10J/cm2). Histological specimens were routinely processed, cut and stained with toluidine blue and mast cell counts performed. No significant statistic difference was found between groups as to the number of degranulated, non-degradulated or total mast cells. Greater mean values were found for degranulated mast cells in the Anemia + LED. LED irradiation on healthy specimens resulted in a smaller number of degranulated mast cells. Our results leads to conclude that there are no significant differences in the number of mast cells seven days after irradiation following Laser or LED phototherapy.

Further studies on the effect of nitrogen dioxide on mast cells: The effect of the metabolite, nitrite

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

Fujimaki, Hidekazu; Ozawa, Masashi; Bissonnette, E.

1993-05-01

To evaluate the relationship between atmospheric nitrogen dioxide exposure and the development of allergic diseases, the effects of nitrite as a chemical product of inhaled nitrogen dioxide on mast cell functions were investigated. We have studied nitride-induced histamine release from two functionally distinct mast cell populations, namely peritoneal mast cells (PMC) and intestinal mucosal mast cells (IMMC) of Nippostrongylus brasiliensis-infected rats. High concentrations of nitrite alone (10, 20, and 50 mM) induced histamine release from IMMC, but not from PMC. Moreover, histamine release from PMC and IMMC stimulated with sensitizing antigen was significantly enhanced by pretreatment with 50 mM nitritemore » or nitrate. No differences in histamine release from nitrite-treated and control PMC were seen below 1 mM. To investigate the effect of nitrite on tumor cell cytotoxic activity, PMC were incubated with various concentrations of nitrite. Pretreatment with 5 and 50 mM nitrite markedly depressed tumor necrosis factor (TNF)-[alpha]-dependent natural cytotoxicity of PMC for the tumor target WEHI-164. Thus, high concentrations of nitrite enhanced mast cell histamine release, but depressed TNF-[alpha]-dependent cytotoxicity. However, low concentrations of nitrite (<1 mM) that would normally be produced by short-term atmospheric exposure to nitrogen dioxide may have no significant effects on mast cell functions. 27 refs., 3 figs., 1 tab.« less

Helicobacter pylori neutrophil-activating protein induces release of histamine and interleukin-6 through G protein-mediated MAPKs and PI3K/Akt pathways in HMC-1 cells.

PubMed

Tsai, Chung-Che; Kuo, Ting-Yu; Hong, Zhi-Wei; Yeh, Ying-Chieh; Shih, Kuo-Shun; Du, Shin-Yi; Fu, Hua-Wen

2015-01-01

Helicobacter pylori neutrophil-activating protein (HP-NAP) activates several innate leukocytes including neutrophils, monocytes, and mast cells. It has been reported that HP-NAP induces degranulation and interleukin-6 (IL-6) secretion of rat peritoneal mast cells. However, the molecular mechanism is not very clear. Here, we show that HP-NAP activates human mast cell line-1 (HMC-1) cells to secrete histamine and IL-6. The secretion depends on pertussis toxin (PTX)-sensitive heterotrimeric G proteins but not on Toll-like receptor 2. Moreover, HP-NAP induces PTX-sensitive G protein-mediated activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38-mitogen-activated protein kinase (p38 MAPK), and Akt in HMC-1 cells. Inhibition of ERK1/2, p38 MAPK, or phosphatidylinositol 3-kinase (PI3K) suppresses HP-NAP-induced release of histamine and IL-6 from HMC-1 cells. Thus, the activation of HMC-1 cells by HP-NAP is through Gi-linked G protein-coupled receptor-mediated MAPKs and PI3K/Akt pathways.

Dissecting components of population-level variation in seed production and the evolution of masting behavior.

Treesearch

W. D. Koenig; D. Kelly; V. L. Sork; R. P. Duncan; J. S. Elkinton; M.S. Peltonen; R. D. Westfall

2003-01-01

Mast-fruiting or masting behavior is the cumulative result of the reproductive patterns of individuals within a population and thus involves components of individual variability, between-individual synchrony, and endogenous cycles of temporal autocorrelation. Extending prior work by Herrera, we explore the interrelationships of these components using data on individual...

Gypsy moth effects on mast production

Treesearch

Kurt W. Gottschalk

1990-01-01

Gypsy moth outbreaks can have drastic effects on many forest resources and uses. Because the gypsy moth prefers oak foliage, oak stands are the most susceptible to defoliation and resultant damage. The value of oak mast for many wildlife species is high. The high carbohydrate content of acorns provides the energy necessary for winter survival. Loss of mast crops due to...

Within-population spatial synchrony in mast seeding of North American oaks.

Treesearch

A.V. Liebhold; M. Sork; O.N. Peltonen; Westfall R. Bjørnstad; J. Elkinton; M. H. J. Knops

2004-01-01

Mast seeding, the synchronous production of large crops of seeds, has been frequently documented in oak species. In this study we used several North American oak data-sets to quantify within-stand (10 km) synchrony in mast dynamics. Results indicated that intraspecific synchrony in seed production always exceeded interspecific synchrony and was essentially constant...

30 CFR 77.807-2 - Booms and masts; minimum distance from high-voltage lines.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-voltage lines. 77.807-2 Section 77.807-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.807-2 Booms and masts; minimum distance from high-voltage lines. The booms and masts of equipment operated on the surface of any...

Effects of different silvicultural systems on initial soft mast production

Treesearch

Roger W. Perry; Ronald E. Thill; David G. Peitz; Philip A. Tappe

1999-01-01

Recent policy changes by federal land management agencies such as the United States [Department of Agriculture] Forest Service have led to increased use of silvicultural systems other than clearcutting. Because soft mast is an integral part of wildlife habitat and the effects of these alternative silviculture systems on soft mast production are unknown, we evaluated...

Variable Acorn Crops: Responses of White-Tailed Deer and Other Mast Consumers

Treesearch

William J. McShea; Georg Schwede

1993-01-01

We examined movements and behavior of female white-tailed deer (Odocoileus virginianus) relative to the acorn mast-fall from 1986 through 1989 in a mature deciduous forest in Front Royal, Virginia. Ten white-tailed deer with radiotransmitters increased their home range to incorporate acorn-producing areas during mast-fall. Consumption of acorns by...

A mast-seeding desert shrub regulates population dynamics and behavior of its heteromyid dispersers

Treesearch

Janene Auger; Susan E. Meyer; Stephen H. Jenkins

2016-01-01

Granivorous rodent populations in deserts are primarily regulated through precipitation-driven resource pulses rather than pulses associated with mast-seeding, a pattern more common in mesic habitats. We studied heteromyid responses to mast-seeding in the desert shrub blackbrush (Coleogyne ramosissima), a regionally dominant species in the Mojave–Great Basin...

Proliferation of Prostate Stromal Cell Induced by Benign Prostatic Hyperplasia Epithelial Cell Stimulated With Trichomonas vaginalis via Crosstalk With Mast Cell.

PubMed

Kim, Jung-Hyun; Kim, Sang-Su; Han, Ik-Hwan; Sim, Seobo; Ahn, Myoung-Hee; Ryu, Jae-Sook

2016-11-01

Chronic inflammation has a role in the pathogenesis of benign prostatic hyperplasia (BPH) and prostate cancer. Mast cells have been detected in chronic inflammatory infiltrate of the prostate, and it is possible that the interaction between prostate epithelial cells and Trichomonas vaginalis influences the activity of mast cells in the prostate stroma. Activated mast cells might influence the biological functions of nearby tissues and cells. In this study, we investigated whether mast cells reacted with the culture supernatant of BPH epithelial cells infected with T. vaginalis may induce the proliferation of prostate stromal cells. To measure the proliferation of prostate stromal cells in response to chronic inflammation caused by the infection of BPH-1 cells with T. vaginalis, the CCK-8 assay and wound healing assay were used. ELISAs, quantitative real-time PCR, western blotting and immunofluorescence were used to measure the production and expression of inflammatory cytokine and cytokine receptor. BPH-1 cells incubated with live trichomonads produced increased levels of CCL2, IL-1β, IL-6, and CXCL8, and induced the migration of mast cells and monocytes. When the culture supernatant of BPH-1 cells stimulated with trichomonads (TCM) was added to mast cells, they became activated, as confirmed by release of β-hexosaminidase and CXCL8. Prostate stromal cells incubated with the culture supernatant of mast cells activated with TCM (M-TCM) proliferated and expressed increased levels of CXCL8, CCL2, and the cytokine receptors CXCR1 and CCR2. Blocking the chemokine receptors reduced the proliferation of stromal cells and also decreased the production of CXCL8 and CCL2. Moreover, the expression of FGF2, cyclin D1, and Bcl-2 was increased in the proliferated stromal cells stimulated with M-TCM. Additionally, the M-TCM-treated stromal cells were more invasive than control cells. The inflammatory mediators released by BPH epithelial cells in response to infection by trichomonads induce the migration and activation of mast cells. The activated mast cells induce the proliferation of prostate stromal cells via CXCL8-CXCR1 and CCL2-CCR2 signaling. Our results therefore show that the inflammatory response by BPH epithelial cells stimulated with T. vaginalis induce the proliferation of prostate stromal cells via crosstalk with mast cells. Prostate 76:1431-1444, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity

PubMed Central

Naveed, Shams-un-nisa; Clements, Debbie; Jackson, David J.; Philp, Christopher; Billington, Charlotte K.; Soomro, Irshad; Reynolds, Catherine; Harrison, Timothy W.; Johnston, Sebastian L.; Shaw, Dominick E.

2017-01-01

Rationale: Matrix metalloproteinase-1 (MMP-1) and mast cells are present in the airways of people with asthma. Objectives: To investigate whether MMP-1 could be activated by mast cells and increase asthma severity. Methods: Patients with stable asthma and healthy control subjects underwent spirometry, methacholine challenge, and bronchoscopy, and their airway smooth muscle cells were grown in culture. A second asthma group and control subjects had symptom scores, spirometry, and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extracellular matrix was prepared from decellularized airway smooth muscle cultures. MMP-1 protein and activity were assessed. Measurements and Main Results: Airway smooth muscle cells generated pro–MMP-1, which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extracellular matrix, which enhanced subsequent airway smooth muscle growth by 1.5-fold (P < 0.05), which was dependent on MMP-1 activation. In asthma, airway pro–MMP-1 was 5.4-fold higher than control subjects (P = 0.002). Mast cell numbers were associated with airway smooth muscle proliferation and MMP-1 protein associated with bronchial hyperresponsiveness. During exacerbations, MMP-1 activity increased and was associated with fall in FEV1 and worsening asthma symptoms. Conclusions: MMP-1 is activated by mast cell tryptase resulting in a proproliferative extracellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, MMP-1 levels are associated with bronchial hyperresponsiveness, and MMP-1 activation are associated with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing MMP activation, airway smooth muscle growth, and airway responsiveness. PMID:27967204

Mast-cell-releasing tryptase triggers acute lung injury induced by small intestinal ischemia-reperfusion by activating PAR-2 in rats.

PubMed

Gan, Xiaoliang; Liu, Dezhao; Huang, Pinjie; Gao, Wanling; Chen, Xinzhi; Hei, Ziqing

2012-06-01

Mast cell has been demonstrated to be involved in the small intestinal ischemia-reperfusion (IIR) injury, however, the precise role of tryptase released from mast cell on acute lung injury(ALI) induced by IIR remains to be elucidated, our study aimed to observe the roles of tryptase on ALI triggered by IIR and its underlying mechanism. Adult SD rats were randomized into sham-operated group, sole IIR group in which rats were subjected to 75 min superior mesenteric artery occlusion followed by 4 h reperfusion, or IIR being respectively treated with cromolyn sodium, protamine, and compound 48/80. The above agents were, respectively, administrated intravenously 5 min before reperfusion. At the end of experiment, lung tissue was obtained for assays for protein expressions of tryptase and mast cell protease 7 (MCP7) and protease-activated receptor 2 (PAR-2). Pulmonary mast cell number and levels of IL-8 were quantified. Lung histologic injury scores and lung water content were measured. IIR resulted in lung injury evidenced as significant increases in lung histological scores and lung water contents, accompanied with concomitant increases of expressions of tryptase and MCP7, and elevations in PAR-2 expressions and IL-8 levels in lungs. Stabilizing mast cell with cromolyn sodium and inhibiting tryptase with protamine significantly reduced IIR-mediated ALI and the above biochemical changes while activating mast cell with compound 48/80 further aggravated IIR-mediated ALI and the increases of above parameters. Tryptase released from mast cells mediates ALI induced by intestinal ischemia-reperfusion by activating PAR-2 to produce IL-8.

Inhibitory effect of putranjivain A on allergic inflammation through suppression of mast cell activation

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

Kim, Hui-Hun; Park, Seung-Bin; Lee, Soyoung

2014-02-01

A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Putranjivain A (PJA), member of ellagitannin, is known to possess beneficial effects including anti-cancer and anti-viral activities. The aim of the present study was to elucidate whether PJA modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. The study was performed in anaphylaxis mouse model and cultured mast cells. PJA inhibited themore » expression of pro-inflammatory cytokines in immunoglobulin E-stimulated mast cells. PJA reduced this expression by inhibiting nuclear factor (NF)-κB and nuclear factor of activated T cell. The oral administration of PJA reduced systemic and cutaneous anaphylaxis, the release of serum histamine, and the expression of the histamine H{sub 1} receptor. In addition, PJA attenuated the activation of mast cells. PJA inhibited the release of histamine from various types of mast cells by the suppression of intracellular calcium. The inhibitory activity of PJA on the allergic reaction was similar to that of disodium cromoglycate, a known anti-allergic drug. These results suggest that PJA can facilitate the prevention or treatment of allergic inflammatory diseases mediated by mast cells. - Highlights: • PJA reduced the degranulation of mast cells. • PJA inhibited the production of inflammatory cytokines. • The effect of PJA on allergic reaction was comparable to the DSCG. • PJA might be a candidate for the treatment of allergic inflammatory diseases.« less

Inflammation induced by mast cell deficiency rather than the loss of interstitial cells of Cajal causes smooth muscle dysfunction in W/Wv mice

PubMed Central

Winston, John H.; Chen, Jinghong; Shi, Xuan-Zheng; Sarna, Sushil K.

2014-01-01

The initial hypothesis suggested that the interstitial cells of Cajal (ICC) played an essential role in mediating enteric neuronal input to smooth muscle cells. Much information for this hypothesis came from studies in W/Wv mice lacking ICC. However, mast cells, which play critical roles in regulating inflammation in their microenvironment, are also absent in W/Wv mice. We tested the hypothesis that the depletion of mast cells in W/Wv mice generates inflammation in fundus muscularis externa (ME) that impairs smooth muscle reactivity to Ach, independent of the depletion of ICC. We performed experiments on the fundus ME from wild type (WT) and W/Wv mice before and after reconstitution of mast cells by bone marrow transplant. We found that mast cell deficiency in W/Wv mice significantly increased COX-2 and iNOS expression and decreased smooth muscle reactivity to Ach. Mast cell reconstitution or concurrent blockade of COX-2 and iNOS restored smooth muscle contractility without affecting the suppression of c-kit in W/Wv mice. The expression of nNOS and ChAT were suppressed in W/Wv mice; mast cell reconstitution did not restore them. We conclude that innate inflammation induced by mast cell deficiency in W/Wv mice impairs smooth muscle contractility independent of ICC deficiency. The impairment of smooth muscle contractility and the suppression of the enzymes regulating the synthesis of Ach and NO in W/Wv mice need to be considered in evaluating the role of ICC in regulating smooth muscle and enteric neuronal function in W/Wv mice. PMID:24550836

Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4

PubMed Central

Torres-Atencio, Ivonne; Ainsua-Enrich, Erola; de Mora, Fernando; Picado, César; Martín, Margarita

2014-01-01

Background Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle to cause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the refractory period observed in patients with EIB. Objective This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction. Methods We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP) antagonists for EP1–4 were assayed on the activated mast cells. Beta-hexosaminidase release, protein phosphorylation, and calcium mobilization were assessed. Results Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogen-activated protein kinase (MAPK) pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP2 and EP4 receptors, as measured by beta-hexosaminidase release, and consequently calcium influx. Extracellular-signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 phosphorylation were diminished when compared with mannitol activation alone. Conclusions Our data show a protective role for the PGE2 receptors EP2 and EP4 following osmotic changes, through the reduction of human mast cell activity caused by calcium influx impairment and MAP kinase inhibition. PMID:25329458

Mast cells exert pro-inflammatory effects of relevance to the pathophyisology of tendinopathy.

PubMed

Behzad, Hayedeh; Sharma, Aishwariya; Mousavizadeh, Rouhollah; Lu, Alex; Scott, Alex

2013-01-01

We have previously found an increased mast cell density in tendon biopsies from patients with patellar tendinopathy compared to controls. This study examined the influence of mast cells on basic tenocyte functions, including production of the inflammatory mediator prostaglandin E2 (PGE2), extracellular matrix remodeling and matrix metalloproteinase (MMP) gene transcription, and collagen synthesis. Primary human tenocytes were stimulated with an established human mast cell line (HMC-1). Extracellular matrix remodeling was studied by culturing tenocytes in a three-dimensional collagen lattice. Survival/proliferation was assessed with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay. Levels of mRNA for COX-2, COL1A1, MMP1, and MMP7 were determined by quantitative real-time polymerase chain reaction (qPCR). Cox-2 protein level was assessed by Western blot analysis and type I procollagen was detected by immunofluorescent staining. PGE2 levels were determined using an enzyme-linked immunosorbent assay (ELISA). Mast cells stimulated tenocytes to produce increased levels of COX-2 and the pro-inflammatory mediator PGE2, which in turn decreased COL1A1 mRNA expression. Additionally, mast cells reduced the type I procollagen protein levels produced by tenocytes. Transforming growth factor beta 1 (TGF-β1) was responsible for the induction of Cox-2 and PGE2 by tenocytes. Mast cells increased MMP1 and MMP7 transcription and increased the contraction of a three-dimensional collagen lattice by tenocytes, a phenomenon which was blocked by a pan-MMP inhibitor (Batimastat). Our data demonstrate that mast cell-derived PGE2 reduces collagen synthesis and enhances expression and activities of MMPs in human tenocytes.

Cannabinoids reduce granuloma-associated angiogenesis in rats by controlling transcription and expression of mast cell protease-5

PubMed Central

De Filippis, D; Russo, A; D'Amico, A; Esposito, G; Concetta, P; Cinelli, M; Russo, G; Iuvone, T

2008-01-01

Background and purpose: Chronic inflammatory conditions, such as granulomas, are associated with angiogenesis. Mast cells represent the main cell type orchestrating angiogenesis, through the release of their granule content. Therefore, compounds able to modulate mast cell behaviour may be considered as a new pharmacological approach to treat angiogenesis-dependent events. Here, we tested the effect of selective cannabinoid (CB) receptor agonists in a model of angiogenesis-dependent granuloma formation induced by λ-carrageenin in rats. Experimental approach: Granulomas were induced by λ-carrageenin-soaked sponges implanted subcutaneously on the back of male Wistar rats. After 96 h, implants were removed and granuloma formation was measured (wet weight); angiogenesis was evaluated by histological analysis and by the measurement of haemoglobin content. Mast cells in the granulomas were evaluated histologically and by RT-PCR and immunoblotting analysis for mast cell-derived proteins (rat mast cell protease-5 (rMCP-5) and nerve growth factor). Selective CB1 and CB2 receptor agonists, ACEA and JWH-015 (0.001–0.1 mg mL−1), were given locally only once, at the time of implantation. Key results: The CB1 and CB2 receptor agonists decreased the weight and vascularization of granulomas after 96 h. This treatment also reduced mast cell number and activation in granulomatous tissue. Specifically, these compounds prevented the transcription and expression of rMCP-5, a protein involved in sprouting and advance of new blood vessels. Conclusion and implications: Modulation of mast cell function by cannabinoids reduced granuloma formation and associated angiogenesis. Therefore cannabinoid-related drugs may be useful in the management of granulomatous diseases accompanied by angiogenesis. PMID:18552882

PEA and luteolin synergistically reduce mast cell-mediated toxicity and elicit neuroprotection in cell-based models of brain ischemia.

PubMed

Parrella, Edoardo; Porrini, Vanessa; Iorio, Rosa; Benarese, Marina; Lanzillotta, Annamaria; Mota, Mariana; Fusco, Mariella; Tonin, Paolo; Spano, PierFranco; Pizzi, Marina

2016-10-01

The combination of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the family of the N-acylethanolamines, and the flavonoid luteolin has been found to exert neuroprotective activities in a variety of mouse models of neurological disorders, including brain ischemia. Indirect findings suggest that the two molecules can reduce the activation of mastocytes in brain ischemia, thus modulating crucial cells that trigger the inflammatory cascade. Though, no evidence exists about a direct effect of PEA and luteolin on mast cells in experimental models of brain ischemia, either used separately or in combination. In order to fill this gap, we developed a novel cell-based model of severe brain ischemia consisting of primary mouse cortical neurons and cloned mast cells derived from mouse fetal liver (MC/9 cells) subjected to oxygen and glucose deprivation (OGD). OGD exposure promoted both mast cell degranulation and the release of lactate dehydrogenase (LDH) in a time-dependent fashion. MC/9 cells exacerbated neuronal damage in neuron-mast cells co-cultures exposed to OGD. Likewise, the conditioned medium derived from OGD-exposed MC/9 cells induced significant neurotoxicity in control primary neurons. PEA and luteolin pre-treatment synergistically prevented the OGD-induced degranulation of mast cells and reduced the neurotoxic potential of MC/9 cells conditioned medium. Finally, the association of the two drugs promoted a direct synergistic neuroprotection even in pure cortical neurons exposed to OGD. In summary, our results indicate that mast cells release neurotoxic factors upon OGD-induced activation. The association PEA-luteolin actively reduces mast cell-mediated neurotoxicity as well as pure neurons susceptibility to OGD. Copyright © 2016 Elsevier B.V. All rights reserved.

Mast cells and IgE in defense against venoms: Possible "good side" of allergy?

PubMed

Galli, Stephen J; Starkl, Philipp; Marichal, Thomas; Tsai, Mindy

2016-01-01

Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This 'bad side' of mast cells and IgE is so well accepted that it can be difficult to think of them in other contexts, particularly those in which they may have beneficial functions. However, there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells), can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites. Accordingly, allergies often are conceptualized as "misdirected" type 2 immune responses, in which IgE antibodies are produced against any of a diverse group of apparently harmless antigens, as well as against components of animal venoms. Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. In this review, we will describe evidence that mast cells can enhance innate resistance to reptile or arthropod venoms during a first exposure to such venoms. We also will discuss findings indicating that, in mice which survive an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcɛRI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Substance P induces adverse myocardial remodelling via a mechanism involving cardiac mast cells.

PubMed

Meléndez, Giselle C; Li, Jianping; Law, Brittany A; Janicki, Joseph S; Supowit, Scott C; Levick, Scott P

2011-12-01

Substance P and neurokinin A (NKA) are sensory nerve neuropeptides encoded by the TAC1 gene. Substance P is a mast cell secretagogue and mast cells are known to play a role in adverse myocardial remodelling. Therefore, we wondered whether substance P and/or NKA modulates myocardial remodelling via a mast cell-mediated mechanism. Volume overload was induced by aortocaval fistula in TAC1(-/-) mice and their respective wild types. Left ventricular internal diameter of wild-type (WT) fistulas increased by 31.9%; this was prevented in TAC1(-/-) mice (4.2%). Matrix metalloproteinase (MMP) activity was significantly increased in WT fistula mice and was prevented in TAC1(-/-) mice. Myocardial collagen volume fraction was decreased in WT fistula mice; this collagen degradation was not observed in the TAC1(-/-) group. There were no significant differences between any groups in tumour necrosis factor (TNF)-α or cell death. Cardiac mast cells were isolated from rat hearts and stimulated with substance P or NKA. We found that these cells degranulated only to substance P, via the neurokinin-1 receptor. To determine the effect of substance P on mast cells in vivo, volume overload was created in Sprague-Dawley rats treated with the NK-1 receptor antagonist L732138 (5 mg/kg/day) for a period of 3 days. L732138 prevented: (i) increases in cardiac mast cell density; (ii) increased myocardial TNF-α; and (iii) collagen degradation. Our studies suggest that substance P may be important in mediating adverse myocardial remodelling secondary to volume overload by activating cardiac mast cells, leading to increased TNF-α and MMP activation with subsequent degradation of the extracellular matrix.

Substance P induces adverse myocardial remodelling via a mechanism involving cardiac mast cells

PubMed Central

Meléndez, Giselle C.; Li, Jianping; Law, Brittany A.; Janicki, Joseph S.; Supowit, Scott C.; Levick, Scott P.

2011-01-01

Aims Substance P and neurokinin A (NKA) are sensory nerve neuropeptides encoded by the TAC1 gene. Substance P is a mast cell secretagogue and mast cells are known to play a role in adverse myocardial remodelling. Therefore, we wondered whether substance P and/or NKA modulates myocardial remodelling via a mast cell-mediated mechanism. Methods and results Volume overload was induced by aortocaval fistula in TAC1−/− mice and their respective wild types. Left ventricular internal diameter of wild-type (WT) fistulas increased by 31.9%; this was prevented in TAC1−/− mice (4.2%). Matrix metalloproteinase (MMP) activity was significantly increased in WT fistula mice and was prevented in TAC1−/− mice. Myocardial collagen volume fraction was decreased in WT fistula mice; this collagen degradation was not observed in the TAC1−/− group. There were no significant differences between any groups in tumour necrosis factor (TNF)-α or cell death. Cardiac mast cells were isolated from rat hearts and stimulated with substance P or NKA. We found that these cells degranulated only to substance P, via the neurokinin-1 receptor. To determine the effect of substance P on mast cells in vivo, volume overload was created in Sprague-Dawley rats treated with the NK-1 receptor antagonist L732138 (5 mg/kg/day) for a period of 3 days. L732138 prevented: (i) increases in cardiac mast cell density; (ii) increased myocardial TNF-α; and (iii) collagen degradation. Conclusions Our studies suggest that substance P may be important in mediating adverse myocardial remodelling secondary to volume overload by activating cardiac mast cells, leading to increased TNF-α and MMP activation with subsequent degradation of the extracellular matrix. PMID:21908647

Immunoexpression of tryptase-positive mast cells in periapical granulomas and radicular cysts.

PubMed

Costa Neto, H; de Andrade, A L D L; Gordón-Núñez, M A; Freitas, R de A; Galvão, H C

2015-08-01

To evaluate and compare the immunoexpression of tryptase in samples of periapical granulomas (PGs) and radicular cysts (RCs) correlating it with the type of lesion, localization, intensity of the inflammatory infiltrate and thickness of the cystic epithelial lining, in order to gain insight into the phlogistic role of these cells in the lesions studied. Twenty-five PGs and twenty-five RCs obtained from human teeth without endodontic treatment were submitted to morphological and immunohistochemical analysis using anti-tryptase antibody. Mast cells were identified and counted in three regions: intra-epithelial, central/superficial and deep portions. The data were analysed using the Mann-Whitney U-test (P < 0.05). In comparison with RCs, PGs exhibited higher immunoexpression of tryptase-positive mast cells located in both central/superficial and deep regions (P < 0.001 and P < 0.001, respectively). When considering the total number of mast cells and disregarding the location, the number of tryptase-positive mast cells increased gradually from RCs to PGs (P < 0.001). Lesions with inflammatory infiltrate grade III had greater number of tryptase-positive mast cells located in both central/superficial and deep regions than lesions with inflammatory infiltrates grade II (P = 0.045 and P = 0.025). When the location was ignored, the lesions with inflammatory infiltrate grade III also exhibited higher immunostaining of tryptase-positive mast cells (P = 0.01). Tryptase-positive mast cells were present in chronic periapical lesions in a larger number in periapical granulomas than in radicular cysts, in both central/superficial and deep regions. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Characterization and modulation of canine mast cell derived eicosanoids

PubMed Central

Lin, Tzu-Yin; London, Cheryl A.

2013-01-01

Mast cells play an important role in both innate and acquired immunity as well as several pathological conditions including allergy, arthritis and neoplasia. They influence these processes by producing a variety of mediators including cytokines, chemokines and eicosanoids. Very little is currently known about the spectrum of inflammatory mediators, particularly eicosanoids (prostaglandins and leukotrienes), produced by canine mast cells. This is important since modulating mast cell derived eicosanoids may help in the treatment of autoimmune and inflammatory disorders. The purpose of this study was to investigate the spectrum of eicosanoids produced by normal canine mast cells and to evaluate the effects of cytokines and non-steroidal anti-inflammatory mediators (NSAIDS) on eicosanoid production and release. Canine bone marrow derived cultured mast cells (cBMCMCs) expressed COX-1, COX-2, and 5-LOX and synthesized and released PGD2, PGE2, LTB4, and LTC4 following activation by a variety of stimuli. The selective COX-2 NSAIDs carprofen (Rimadyl®) and deracoxib (Deramaxx®) inhibited PGD2 and PGE2 production but only slightly inhibited LTB4 and LTC4. The mixed COX-1/COX-2 inhibitor piroxicam blocked PGD2 and PGE2 production, but upregulated LTC4 following treatment while tepoxilan (Zubrin®), a pan COX/LOX inhibitor, markedly reduced the production of all eicosanoids. The LOX inhibitor nordihydroguaiaretic acid (NDGA) prevented LTB4/LTC4 release and BMBMC degranulation. Pre-incubation of cBMCMCs with IL-4 and SCF sensitized these cells to degranulation in response to substance P. In conclusion, canine BMCMCs produce an array of eicosanoids similar to those produced by mast cells from other species. Tepoxilan appeared to be the most effective NSAID for blocking eicosanoid production and thus may be useful for modulating mast cell mediated responses in dogs. PMID:20036014

Spontaneous locomotor activity correlates with the degranulation of mast cells in the meninges rather than in the thalamus: disruptive effect of cocaine.

PubMed

Larson, Alice A; Thomas, Mark J; McElhose, Alex; Kovács, Katalin J

2011-06-13

Mast cells are located in the central nervous system (CNS) of many mammals and stress induces their degranulation. We postulated that mast cells are associated with wakefulness and stimulatory tone in the CNS, as reflected by spontaneous motor activity. Because stress also precipitates drug-seeking behavior in cocaine addicts, we also postulated that cocaine manifests its effects through this relationship. We investigated the influence of single and repeated injections of cocaine on circulating corticosterone, motor activity and degranulation of mast cells in both the thalamus and meninges of mice. Mice were subjected to 5 consecutive days of cocaine or saline followed by a single injection of cocaine or saline 11 days later. Spontaneous locomotor activity was measure for 1h after the final injection before death. Neither a single injection nor prior treatment with cocaine increased motor activity compared to saline-injected controls, however, repeated administration of cocaine induced a significant sensitization to its behavioral effect when delivered 11 days later. In mice that received only saline, motor activity correlated positively with mast cell degranulation in the meninges but not in the thalamus. Cocaine, regardless of the treatment schedule, disrupted this correlation. The concentration of corticosterone did not differ amongst groups and did not correlate with either behavior or mast cell parameters in any group. The correlation between behavioral activity and the mast cell degranulation in the meninges suggests that these parameters are linked. The disruptive effect of cocaine on this relationship indicates a role downstream from mast cells in the regulation of motor activity. Copyright © 2011 Elsevier B.V. All rights reserved.

Evidence for autocrine and paracrine regulation of allergen-induced mast cell mediator release in the guinea pig airways.

PubMed

Yu, Li; Liu, Qi; Canning, Brendan J

2018-03-05

Mast cells play an essential role in immediate type hypersensitivity reactions and in chronic allergic diseases of the airways, including asthma. Mast cell mediator release can be modulated by locally released autacoids and circulating hormones, but surprisingly little is known about the autocrine effects of mediators released upon mast cell activation. We thus set out to characterize the autocrine and paracrine effects of mast cell mediators on mast cell activation in the guinea pig airways. By direct measures of histamine, cysteinyl-leukotriene and thromboxane release and with studies of allergen-evoked contractions of airway smooth muscle, we describe a complex interplay amongst these autacoids. Notably, we observed an autocrine effect of the cysteinyl-leukotrienes acting through cysLT 1 receptors on mast cell leukotriene release. We confirmed the results of previous studies demonstrating a marked enhancement of mast cell mediator release following cyclooxygenase inhibition, but we have extended these results by showing that COX-2 derived eicosanoids inhibit cysteinyl-leukotriene release and yet are without effect on histamine release. Given the prominent role of COX-1 inhibition in aspirin-sensitive asthma, these data implicate preformed mediators stored in granules as the initial drivers of these adverse reactions. Finally, we describe the paracrine signaling cascade leading to thromboxane synthesis in the guinea pig airways following allergen challenge, which occurs indirectly, secondary to cysLT 1 receptor activation on structural cells and/ or leukocytes within the airway wall, and a COX-2 dependent synthesis of the eicosanoid. The results highlight the importance of cell-cell and autocrine interactions in regulating allergic responses in the airways. Copyright © 2017. Published by Elsevier B.V.

Statistical analysis of electromagnetic radiation measurements in the vicinity of GSM/UMTS base station antenna masts.

PubMed

Koprivica, Mladen; Neskovic, Natasa; Neskovic, Aleksandar; Paunovic, George

2014-01-01

As a result of dense installations of public mobile base station, additional electromagnetic radiation occurs in the living environment. In order to determine the level of radio-frequency radiation generated by base stations, extensive electromagnetic field strength measurements were carried out for 664 base station locations. Base station locations were classified into three categories: indoor, masts and locations with installations on buildings. Having in mind the large percentage (47 %) of sites with antenna masts, a detailed analysis of this location category was performed, and the measurement results were presented. It was concluded that the total electric field strength in the vicinity of base station antenna masts in no case exceeded 10 V m(-1), which is quite below the International Commission on Non-Ionizing Radiation Protection reference levels. At horizontal distances >50 m from the mast bottom, the median and maximum values were <1 and 2 V m(-1), respectively.

The Suppressive Activity of Fucofuroeckol-A Derived from Brown Algal Ecklonia stolonifera Okamura on UVB-Induced Mast Cell Degranulation

PubMed Central

Vo, Thanh Sang; Kim, Se-Kwon; Ngo, Dai Hung; Yoon, Na-Young; Bach, Long Giang; Hang, Nguyen Thi Nhat; Ngo, Dai Nghiep

2018-01-01

UV light, especially UVB, is known as a trigger of allergic reaction, leading to mast cell degranulation and histamine release. In this study, phlorotannin Fucofuroeckol-A (F-A) derived from brown algal Ecklonia stolonifera Okamura was evaluated for its protective capability against UVB-induced allergic reaction in RBL-2H3 mast cells. It was revealed that F-A significantly suppress mast cell degranulation via decreasing histamine release as well as intracellular Ca2+ elevation at the concentration of 50 μM. Moreover, the inhibitory effect of F-A on IL-1β and TNF-α productions was also evidenced. Notably, the protective activity of F-A against mast cell degranulation was found due to scavenging ROS production. Accordingly, F-A from brown algal E. stolonifera was suggested to be promising candidate for its protective capability against UVB-induced allergic reaction. PMID:29300311

Tests of wildlife habitat models to evaluate oak-mast production

USGS Publications Warehouse

Schroeder, R.L.; Vangilder, L.D.

1997-01-01

We measured oak-mast production and forest structure and composition in the Ozark Mountains of Missouri and tested the accuracy of oak-mast prediction variables from 5 Habitat Suitability Index (HSI) species models. Acorn production was positively associated with several measures of abundance and canopy cover of oak trees, and with an index of mast production for all 5 HSI models. We developed 2 modified oak-mast models, based on inputs related to either oak tree density or oak canopy cover and diversity of oak tree species. The revised models accounted for 22-32% of the variance associated with acorn abundance. Future tests of HSI models should consider: (1) the concept of upper limits imposed by habitat and the effects of nonhabitat factors; (2) the benefits of a top-down approach to model development; and (3) testing models across broad geographic regions.

A field programmable gate array unit for the diagnosis and control of neoclassical tearing modes on MAST

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

O'Gorman, T.; Gibson, K. J.; Snape, J. A.

2012-10-15

A real-time system has been developed to trigger both the MAST Thomson scattering (TS) system and the plasma control system on the phase and amplitude of neoclassical tearing modes (NTMs), extending the capabilities of the original system. This triggering system determines the phase and amplitude of a given NTM using magnetic coils at different toroidal locations. Real-time processing of the raw magnetic data occurs on a low cost field programmable gate array (FPGA) based unit which permits triggering of the TS lasers on specific amplitudes and phases of NTM evolution. The MAST plasma control system can receive a separate triggermore » from the FPGA unit that initiates a vertical shift of the MAST magnetic axis. Such shifts have fully removed m/n= 2/1 NTMs instabilities on a number of MAST discharges.« less

Current options in the treatment of mast cell mediator-related symptoms in mastocytosis.

PubMed

Escribano, Luis; Akin, Cem; Castells, Mariana; Schwartz, Lawrence B

2006-01-01

Patients with mastocytosis have symptoms related to the tissue response to the release of mediators from mast cells (MC), local mast cell burden or associated non-mast cell hematological disorders. MC contain an array of biologically active mediators in their granules, which are preformed and stored. MC are also able to produce newly generated membrane-derived lipid mediators and are a source of multifunctional cytokines. Mediator-related symptoms can include pruritus, flushing, syncope, gastric distress, nausea and vomiting, diarrhea, bone pain and neuropsychiatric disturbances; these symptoms are variably controlled by adequate medications. Management of patients within all categories of mastocytosis includes: a) a careful counseling of patients (parents in pediatric cases) and care providers, b) avoidance of factors triggering acute mediator release, c) treatment of acute and chronic MC-mediator symptoms and, if indicated, d) an attempt for cytoreduction and treatment of organ infiltration by mast cells.

A Role for Human Skin Mast Cells in Dengue Virus Infection and Systemic Spread.

PubMed

Troupin, Andrea; Shirley, Devon; Londono-Renteria, Berlin; Watson, Alan M; McHale, Cody; Hall, Alex; Hartstone-Rose, Adam; Klimstra, William B; Gomez, Gregorio; Colpitts, Tonya M

2016-12-01

Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious global human disease and mortality. Skin immune cells are an important component of initial DENV infection and systemic spread. Here, we show that mast cells are a target of DENV in human skin and that DENV infection of skin mast cells induces degranulation and alters cytokine and growth factor expression profiles. Importantly, to our knowledge, we also demonstrate for the first time that DENV localizes within secretory granules in infected skin mast cells. In addition, DENV within extracellular granules was infectious in vitro and in vivo, trafficking through lymph to draining lymph nodes in mice. We demonstrate an important role for human skin mast cells in DENV infection and identify a novel mechanism for systemic spread of DENV infection from the initial peripheral mosquito injection site. Copyright © 2016 by The American Association of Immunologists, Inc.

Beyond apoptosis: The mechanism and function of phosphatidylserine asymmetry in the membrane of activating mast cells

PubMed Central

Rysavy, Noel M.; Shimoda, Lori M. N.; Dixon, Alyssa M.; Speck, Mark; Stokes, Alexander J.; Turner, Helen; Umemoto, Eric Y.

2014-01-01

Loss of plasma membrane asymmetry is a hallmark of apoptosis, but lipid bilayer asymmetry and loss of asymmetry can contribute to numerous cellular functions and responses that are independent of programmed cell death. Exofacial exposure of phosphatidylserine occurs in lymphocytes and mast cells after antigenic stimulation and in the absence of apoptosis, suggesting that there is a functional requirement for phosphatidylserine exposure in immunocytes. In this review we examine current ideas as to the nature of this functional role in mast cell activation. Mechanistically, there is controversy as to the candidate proteins responsible for phosphatidylserine translocation from the internal to external leaflet, and here we review the candidacies of mast cell PLSCR1 and TMEM16F. Finally we examine the potential relationship between functionally important mast cell membrane perturbations and phosphatidylserine exposure during activation. PMID:25759911

Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul That Continues Today.

PubMed

Caslin, Heather L; Kiwanuka, Kasalina N; Haque, Tamara T; Taruselli, Marcela T; MacKnight, H Patrick; Paranjape, Anuya; Ryan, John J

2018-01-01

Mast cells are tissue resident, innate immune cells with heterogenous phenotypes tuned by cytokines and other microenvironmental stimuli. Playing a protective role in parasitic, bacterial, and viral infections, mast cells are also known for their role in the pathogenesis of allergy, asthma, and autoimmune diseases. Here, we review factors controlling mast cell activation, with a focus on receptor signaling and potential therapies for allergic disease. Specifically, we will discuss our work with FcεRI and FγR signaling, IL-4, IL-10, and TGF-β1 treatment, and Stat5. We conclude with potential therapeutics for allergic disease. Much of these efforts have been influenced by the work of Bill Paul. With many mechanistic targets for mast cell activation and different classes of therapeutics being studied, there is reason to be hopeful for continued clinical progress in this area.

30 CFR 57.7051 - Loose objects on the mast or drill platform.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Loose objects on the mast or drill platform. 57... Drilling and Rotary Jet Piercing Drilling-Surface and Underground § 57.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the...

30 CFR 57.7051 - Loose objects on the mast or drill platform.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Loose objects on the mast or drill platform. 57... Drilling and Rotary Jet Piercing Drilling-Surface and Underground § 57.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the...

30 CFR 57.7051 - Loose objects on the mast or drill platform.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Loose objects on the mast or drill platform. 57... Drilling and Rotary Jet Piercing Drilling-Surface and Underground § 57.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the...

Attachment in Adults with Intellectual Disabilities: Preliminary Investigation of the Psychometric Properties of the Manchester Attachment Scale-Third Party Observational Measure

ERIC Educational Resources Information Center

Penketh, Victoria; Hare, Dougal Julian; Flood, Andrea; Walker, Samantha

2014-01-01

Background: The Manchester Attachment Scale-Third party observational measure (MAST) was developed to assess secure attachment style for adults with intellectual disabilities. The psychometric properties of the MAST were examined. Materials and Methods: Professional carers (N = 40) completed the MAST and measures related to the construct of…

Machine Tool Advanced Skills Technology Program (MAST). Overview and Methodology.

ERIC Educational Resources Information Center

Texas State Technical Coll., Waco.

The Machine Tool Advanced Skills Technology Program (MAST) is a geographical partnership of six of the nation's best two-year colleges located in the six states that have about one-third of the density of metals-related industries in the United States. The purpose of the MAST grant is to develop and implement a national training model to overcome…

Seedling establishment in a masting desert shrub parallels the pattern for forest trees

Treesearch

Susan E. Meyer; Burton K. Pendleton

2015-01-01

The masting phenomenon along with its accompanying suite of seedling adaptive traits has been well studied in forest trees but has rarely been examined in desert shrubs. Blackbrush (Coleogyne ramosissima) is a regionally dominant North American desert shrub whose seeds are produced in mast events and scatter-hoarded by rodents. We followed the fate of seedlings in...

Reciprocal regulation of ARPP-16 by PKA and MAST3 kinases provides a cAMP-regulated switch in protein phosphatase 2A inhibition

PubMed Central

Musante, Veronica; Li, Lu; Kanyo, Jean; Lam, Tukiet T; Colangelo, Christopher M; Cheng, Shuk Kei; Brody, A Harrison; Greengard, Paul; Le Novère, Nicolas; Nairn, Angus C

2017-01-01

ARPP-16, ARPP-19, and ENSA are inhibitors of protein phosphatase PP2A. ARPP-19 and ENSA phosphorylated by Greatwall kinase inhibit PP2A during mitosis. ARPP-16 is expressed in striatal neurons where basal phosphorylation by MAST3 kinase inhibits PP2A and regulates key components of striatal signaling. The ARPP-16/19 proteins were discovered as substrates for PKA, but the function of PKA phosphorylation is unknown. We find that phosphorylation by PKA or MAST3 mutually suppresses the ability of the other kinase to act on ARPP-16. Phosphorylation by PKA also acts to prevent inhibition of PP2A by ARPP-16 phosphorylated by MAST3. Moreover, PKA phosphorylates MAST3 at multiple sites resulting in its inhibition. Mathematical modeling highlights the role of these three regulatory interactions to create a switch-like response to cAMP. Together, the results suggest a complex antagonistic interplay between the control of ARPP-16 by MAST3 and PKA that creates a mechanism whereby cAMP mediates PP2A disinhibition. DOI: http://dx.doi.org/10.7554/eLife.24998.001 PMID:28613156

Protein tyrosine phosphatase 1B (PTP1B) is dispensable for IgE-mediated cutaneous reaction in vivo.

PubMed

Yang, Ting; Xie, Zhongping; Li, Hua; Yue, Lei; Pang, Zheng; MacNeil, Adam J; Tremblay, Michel L; Tang, Jin-Tian; Lin, Tong-Jun

2016-01-01

Mast cells play a critical role in allergic reactions. The cross-linking of FcεRI-bound IgE with multivalent antigen initiates a cascade of signaling events leading to mast cell activation. It has been well-recognized that cross linking of FcεRI mediates tyrosine phosphorylation. However, the mechanism involved in tyrosine dephosphorylation in mast cells is less clear. Here we demonstrated that protein tyrosine phosphatase 1B (PTP1B)-deficient mast cells showed increased IgE-mediated phosphorylation of the signal transducer and activator of transcription 5 (STAT5) and enhanced production of CCL9 (MIP-1γ) and IL-6 in IgE-mediated mast cells activation in vitro. However, IgE-mediated calcium mobilization, β-hexaosaminidase release (degranulation), and phosphorylation of IκB and MAP kinases were not affected by PTP1B deficiency. Furthermore, PTP1B deficient mice showed normal IgE-dependent passive cutaneous anaphylaxis and late phase cutaneous reactions in vivo. Thus, PTP1B specifically regulates IgE-mediated STAT5 pathway, but is redundant in influencing mast cell function in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of mast cells in bronchial contraction in nonallergic obstructive lung pathology.

PubMed

Kuzubova, Nataliya A; Lebedeva, Elena S; Titova, Olga N; Fedin, Anatoliy N; Dvorakovskaya, Ivetta V

2017-01-01

The role of mast cells in contractile bronchial smooth muscle activity has been evaluated in a model of chronic obstructive pulmonary disease induced in rats that were intermittently exposed to nitrogen dioxide (NO 2 ) for 60 days. Starting from the 31st day, one group of rats inhaled sodium cromoglycate before exposure to NO 2 to stabilize mast cell membranes. The second group (control) was not treated. Isometric smooth muscle contraction was analysed in isolated bronchial samples in response to nerve and smooth muscle stimulation. Histological analysis revealed large numbers of mast cells in lung tissue of COPD model rats. The inhibition of mast cell degranulation by sodium cromoglycate prevented the development of nerve-stimulated bronchial smooth muscle hyperactivity in COPD model rats. Histamine or adenosine-induced hyperactivity on nerve stimulation was also inhibited by sodium cromoglycate in bronchial smooth muscle in both control and COPD model rats. This suggests that the mechanism of contractile activity enhancement of bronchial wall smooth muscle cells may be mediated through the activation of resident mast cells transmembrane adenosine receptors resulting in their partial degranulation, with the released histamine acting upon histamine H1-receptors which trigger reflex pathways via intramural ganglion neurons.