Science.gov

Sample records for eosinophil granule-derived major

  1. Eosinophil granule-derived major basic protein induces IL-8 expression in human intestinal myofibroblasts.

    PubMed

    Furuta, G T; Ackerman, S J; Varga, J; Spiess, A M; Wang, M Y; Wershil, B K

    2000-10-01

    Eosinophil infiltration occurs in a variety of allergic and inflammatory diseases. The release of preformed mediators from eosinophils may contribute to inflammatory responses. We investigated the ability of eosinophil-derived major basic protein and eosinophil-derived neurotoxin to stimulate production of IL-8 from intestinal myofibroblasts. Intestinal myofibroblasts (18-Co cells) were incubated with major basic protein, eosinophil-derived neurotoxin, or a synthetic analogue of major basic protein, poly-L-arginine. Immunoreactive IL-8 was measured by ELISA and IL-8 mRNA levels were analysed by Northern blot or reverse transcription-polymerase chain assay. Major basic protein induced IL-8 mRNA production and release of significant levels of IL-8 immunoreactive protein. By contrast, eosinophil-derived neurotoxin stimulated little IL-8 release. The induction of IL-8 mRNA by poly-L-arginine was significantly inhibited by actinomycin D. These findings demonstrate a novel interaction between eosinophils and intestinal fibroblasts that may be involved in the pathogenesis of diseases associated with tissue eosinophilia. PMID:11012615

  2. Major basic protein, but not eosinophil cationic protein or eosinophil protein X, is related to atopy in cystic fibrosis.

    PubMed

    Koller, D Y; Halmerbauer, G; Müller, J; Frischer, T; Schierl, M

    1999-10-01

    Increased eosinophil granule proteins have been described in serum and sputum samples of patients with cystic fibrosis (CF). It has been assumed that eosinophil degranulation is enhanced in atopic subjects - as in asthmatics. Since in CF no differences in eosinophil cationic protein (ECP), eosinophil protein X (EPX), and eosinophil peroxidase between atopic and nonatopic subjects have been detected, we investigated whether major basic protein (MBP) is increased in serum and sputum samples derived from atopic (n = 14) compared with nonatopic CF subjects (n = 26). In CF patients, high mean serum (sputum) levels of ECP 29.7 microg/l (2.7 mg/l), EPX 53.7 microg/l (7.9 mg/l), and MBP 984.6 microg/l but low sputum MBP levels (57.4 microg/l) were measured. In addition, in serum and in sputum samples, a significant correlation between MBP and ECP (P<0.03 and P<0.0001, respectively) or EPX (P<0.05 and P<0.0004, respectively) was detected. By subdivision of the patients into allergic and nonallergic subjects, significant differences were found for serum MBP values only(mean 1382.2 microg/l vs. 770.5 microg/l; P<0.0001), but not for ECP or EPX serum levels or for eosinophil proteins in sputum. Although no differences between atopic and nonatopic CF patients in ECP and EPX were found, serum MBP levels were higher in patients sensitized to inhalant allergens than in nonsensitized subjects. These results indicate differential release of eosinophil granule proteins in peripheral blood from eosinophils, and they also indicate that MBP in serum likely is to be a better discriminator of atopy in CF. PMID:10536888

  3. Major Basic Protein from Eosinophils and Myeloperoxidase from Neutrophils Are Required for Protective Immunity to Strongyloides stercoralis in Mice ▿

    PubMed Central

    O'Connell, Amy E.; Hess, Jessica A.; Santiago, Gilberto A.; Nolan, Thomas J.; Lok, James B.; Lee, James J.; Abraham, David

    2011-01-01

    Eosinophils and neutrophils contribute to larval killing during the primary immune response, and neutrophils are effector cells in the secondary response to Strongyloides stercoralis in mice. The objective of this study was to determine the molecular mechanisms used by eosinophils and neutrophils to control infections with S. stercoralis. Using mice deficient in the eosinophil granule products major basic protein (MBP) and eosinophil peroxidase (EPO), it was determined that eosinophils kill the larvae through an MBP-dependent mechanism in the primary immune response if other effector cells are absent. Infecting PHIL mice, which are eosinophil deficient, with S. stercoralis resulted in development of primary and secondary immune responses that were similar to those of wild-type mice, suggesting that eosinophils are not an absolute requirement for larval killing or development of secondary immunity. Treating PHIL mice with a neutrophil-depleting antibody resulted in a significant impairment in larval killing. Naïve and immunized mice with neutrophils deficient in myeloperoxidase (MPO) infected with S. stercoralis had significantly decreased larval killing. It was concluded that there is redundancy in the primary immune response, with eosinophils killing the larvae through an MBP-dependent mechanism and neutrophils killing the worms through an MPO-dependent mechanism. Eosinophils are not required for the development or function of secondary immunity, but MPO from neutrophils is required for protective secondary immunity. PMID:21482685

  4. Diagnostic utility of major basic protein, eotaxin-3, and leukotriene enzyme staining in eosinophilic esophagitis

    PubMed Central

    Dellon, Evan S.; Chen, Xiaoxin; Miller, C. Ryan; Woosley, John T.; Shaheen, Nicholas J.

    2013-01-01

    Objectives Features of eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) overlap. We aimed to determine whether staining for tissue biomarkers would differentiate EoE from GERD, suggesting utility for diagnosis of EoE. Methods In this case-control study, EoE patients defined by consensus guidelines were compared to GERD patients with eosinophils on esophageal biopsy. Immunohistochemistry was performed for major basic protein (MBP), eotaxin-3, leukotriene A4 hydrolase (LTA4H), and leukotriene C4 synthase (LTC4S). After masking, the maximum staining density (cells/mm2) was quantified for each marker and compared between groups. Receiver operator characteristic curves were constructed, and the area under the curve (AUC) calculated to assess the diagnostic utility of each of the biomarkers alone and in combination with eosinophil counts. Results There were 51 EoE cases (mean age 24; mean 143 eos/hpf) and 54 GERD controls (mean age 34; mean 20 eos/hpf). The MBP density was higher in EoE than in GERD (1479 vs 59 cells/mm2; p<0.001), as was the eotaxin-3 density (2219 vs 479; p<0.001). There were no differences for LTA4H and LTC4S. MBP density and eosinophil count correlated (R=0.81; p<0.001); correlation with eotaxin-3 was weaker (R=0.25; p=0.01). The AUC for diagnosis of EoE was 0.96 for MBP, 0.87 for eotaxin-3, 0.58 for LTA4H, 0.66 for LTC4S, and 0.99 for the combination of MBP, eotaxin-3, and eosinophil count. Conclusions Patients with EoE had substantially higher levels of MBP and eotaxin-3 staining than GERD patients. These markers may have utility as a diagnostic assay for EoE. PMID:22777338

  5. Roles and Regulation of Gastrointestinal Eosinophils in Immunity and Disease

    PubMed Central

    Jung, YunJae; Rothenberg, Marc E.

    2014-01-01

    Eosinophils have been considered to be destructive end-stage effector cells that have a role in parasitic infections and allergy reactions by the release of their granule-derived cytotoxic proteins. However, an increasing number of experimental observations indicate that eosinophils also are multifunctional leukocytes involved in diverse inflammatory and physiologic immune responses. Under homeostatic conditions, eosinophils are particularly abundant in the lamina propria of the gastrointestinal tract where their involvement in various biological processes within the gastrointestinal tract has been posited. In this review, we summarize the molecular steps involved in eosinophil development and describe eosinophil trafficking to the gastrointestinal tract. We synthesize the current findings on the phenotypic and functional properties of gastrointestinal eosinophils and the accumulating evidence that they have a contributory role in gastrointestinal disorders, with a focus on primary eosinophilic gastrointestinal disorders. Finally, we discuss the potential role of eosinophils as modulators of the intestinal immune system. PMID:25049430

  6. CD63 is tightly associated with intracellular, secretory events chaperoning piecemeal degranulation and compound exocytosis in human eosinophils.

    PubMed

    Carmo, Lívia A S; Bonjour, Kennedy; Ueki, Shigeharu; Neves, Josiane S; Liu, Linying; Spencer, Lisa A; Dvorak, Ann M; Weller, Peter F; Melo, Rossana C N

    2016-08-01

    Eosinophil activation leads to secretion of presynthesized, granule-stored mediators that determine the course of allergic, inflammatory, and immunoregulatory responses. CD63, a member of the transmembrane-4 glycoprotein superfamily (tetraspanins) and present on the limiting membranes of eosinophil-specific (secretory) granules, is considered a potential surface marker for eosinophil degranulation. However, the intracellular secretory trafficking of CD63 in eosinophils and other leukocytes is not understood. Here, we provide a comprehensive investigation of CD63 trafficking at high resolution within human eosinophils stimulated with inflammatory stimuli, CCL11 and tumor necrosis factor α, which induce distinctly differing secretory processes in eosinophils: piecemeal degranulation and compound exocytosis, respectively. By using different transmission electron microscopy approaches, including an immunonanogold technique, for enhanced detection of CD63 at subcellular compartments, we identified a major intracellular pool of CD63 that is directly linked to eosinophil degranulation events. Transmission electron microscopy quantitative analyses demonstrated that, in response to stimulation, CD63 is concentrated within granules undergoing secretion by piecemeal degranulation or compound exocytosis and that CD63 tracks with the movements of vesicles and granules in the cytoplasm. Although CD63 was observed at the cell surface after stimulation, immunonanogold electron microscopy revealed that a strong CD63 pool remains in the cytoplasm. It is remarkable that CCL11 and tumor necrosis factor α triggered increased formation of CD63(+) large vesiculotubular carriers (eosinophil sombrero vesicles), which fused with granules in the process of secretion, likely acting in the intracellular translocation of CD63. Altogether, we identified active, intracellular CD63 trafficking connected to eosinophil granule-derived secretory pathways. This is important for understanding the

  7. Human eosinophil major basic protein, a mediator of allergic inflammation, is expressed by alternative splicing from two promoters.

    PubMed Central

    Li, M S; Sun, L; Satoh, T; Fisher, L M; Spry, C J

    1995-01-01

    Human eosinophil major basic protein (MBP) is one of the principal mediators of injury to parasites and tissues in allergic inflammation. MBP is stored in eosinophil crystalloid granules and released with other granule constituents during eosinophil action. Previous studies have identified an MBP gene promoter that generates a 1.0 kb mRNA transcript encoding MBP preproprotein which undergoes processing to the mature storage form. To investigate how the MBP gene is regulated, we have examined the identity and levels of the MBP transcripts both in precursor cells and in blood eosinophils. It was found that the gene was expressed from two upstream promoters, a distal promoter P1 in addition to the previously described promoter P2. Evidence for the second promoter was initially provided by isolation from a human HL-60 leukaemic cell cDNA library of a novel 1.6 kb MBP cDNA that was distinct from the known 1.0 kb cDNA. The complete nucleotide sequence of the 1.6 kb cDNA was determined, and showed that the two cDNAs had identical coding and 3' untranslated regions but differed in their 5' sequences. By isolating and sequencing MBP genomic clones from an arrayed chromosome 11 library, it was demonstrated that the MBP gene is composed of nine upstream exons and five coding exons. The 1.6 and 1.0 kb cDNAs arise by differential splicing of alternate MBP transcripts from promoters P1 and P2 respectively, located 32 kb apart in the genomic DNA. Primer extension analysis identified two transcription start sites at P1, neither associated with a typical TATA box motif. Northern blotting and reverse-transcription PCR analysis showed that the 1.0 kb mRNA was present at higher levels than the 1.6 kb species in immature cells including HL-60 and bone-marrow cells. By contrast, low levels of 1.6 kb mRNA transcripts predominated in differentiated blood eosinophils. The results are compatible with differential use of P1 and P2 promoters as a mechanism for regulation of MBP expression

  8. Reslizumab for pediatric eosinophilic esophagitis.

    PubMed

    Walsh, Garry M

    2010-07-01

    Pediatric eosinophilic esophagitis is an inflammatory condition associated with marked eosinophil accumulation in the mucosal tissues of the esophagus. Eosinophils are major proinflammatory cells thought to make a major contribution to allergic diseases that affect the upper and lower airways, skin and GI tract. IL-5 is central to eosinophil maturation and release from the bone marrow, and their subsequent accumulation, activation and persistence in the tissues. Reslizumab (Cinquil, Ception Therapeutics Inc., PA, USA) is a humanized monoclonal antibody with potent IL-5 neutralizing effects that represents a potential treatment for eosinophilic diseases. This article considers the current status of the clinical development of reslizumab for pediatric eosinophilic esophagitis. PMID:20636000

  9. Leukemia -- Eosinophilic

    MedlinePlus

    ... Leukemia - Eosinophilic: Overview Request Permissions Print to PDF Leukemia - Eosinophilic: Overview Approved by the Cancer.Net Editorial ... Platelets that help the blood to clot About leukemia Types of leukemia are named after the specific ...

  10. [Eosinophilic esophagitis].

    PubMed

    Couto, Mariana; Rodrigues, Susana; Piedade, Susana; Gaspar, Ângela; Morais-Almeida, Mário; Macedo, Guilherme

    2011-12-01

    Eosinophilic esophagitis (EE) is an inflammatory disease of the esophagus characterized by significant and isolated infiltration of the esophageal mucosa by eosinophils, associated with clinical symptoms of esophageal dysfunction, affecting children and adults. It is an increasingly frequent cause of symptoms similar to gastroesophageal reflux disease but refractory to anti-acid therapeutic. It is commonly associated with food allergies or other atopic diseases. Since there are no symptoms, signs, serological biomarkers or endoscopic findings pathognomonic of EE, the diagnosis requires a high degree of suspicion; moreover, due to its chronic relapsing nature the potential to cause major esophageal structural changes, its early recognition and close cooperation between gastroenterologists and immunoallergologists is essential for the timely institution of appropriate therapy. The treatment is based on two main strategies: diet and / or pharmacotherapy, depending on the co-existence of sensitization to food allergens. It is our aim to review this issue, considering recent guidelines, as well as propose a diagnostic and therapeutic algorithm. PMID:22863504

  11. Eosinophilic Disorders

    MedlinePlus

    ... parasites , particularly ones that invade tissue, cause eosinophilia. Cancers that cause eosinophilia include Hodgkin lymphoma , leukemia , and myeloproliferative disorders . If the number of eosinophils is only ...

  12. EoE (Eosinophilic Esophagitis)

    MedlinePlus

    ... EGIDs Eosinophilic Fasciitis Eosinophilic Pneumonia Eosinophilic Cystitis Eosinophilic Granulomatosis with Polyangiitis Hypereosinophilic Syndrome Eosinophilia-Myalgia Syndrome Resources For Patients ...

  13. Eosinophilic esophagitis

    PubMed Central

    Gupte, Anand R; Draganov, Peter V

    2009-01-01

    Eosinophilic esophagitis is increasingly recognized in adults. The diagnosis is based on the presence of both typical symptoms and pathologic findings on esophageal biopsy. Patients usually present with dysphagia, food impaction and/or reflux-like symptoms, and biopsy of the esophagus shows more than 15 eosinophils per high-power field. In addition, it is essential to exclude the presence of known causes of tissue eosinophilia such as gastroesophageal reflux disease, infections, malignancy, collagen vascular diseases, hypersensitivity, and inflammatory bowel disease. There are no standardized protocols for the therapy of eosinophilic esophagitis. A variety of therapeutic approaches including acid suppression, dietary modifications, topical corticosteroids and endoscopic dilation can be used alone or in combination. PMID:19115464

  14. Eosinophilic colitis.

    PubMed

    Dionísio de Sousa, Isabel José; Bonito, Nuno; Pais, Ana; Gervásio, Helena

    2016-01-01

    A 57-year-old man, diagnosed with colon cancer stage III in July/2010, underwent surgery and received adjuvant chemotherapy with FOLFOX 4 (5-fluorouracil; calcium folinate and oxaliplatin), which ended in March/2011 after 12-cycles. It was then decided to maintain periodical surveillance. About 1 year later, the patient developed several episodes of diarrhoea, mainly during the night, and presented persistent peripheral eosinophilia in the blood count (range 585-1300 eosinophils/µL). Colonoscopy was performed, with the histological result showing eosinophilic infiltration of the colon, compatible with eosinophilic colitis. The patient was treated with a short course of budesonide, achieving resolution of symptoms, and has remained asymptomatic. PMID:26957036

  15. Eosinophilic Esophagitis

    PubMed Central

    Furuta, Glenn T.; Katzka, David A.

    2016-01-01

    Once considered a rare condition, eosinophilic esophagitis is now one of the most common conditions diagnosed during the assessment of feeding problems in children and during the evaluation of dysphagia and food impaction in adults.1 The entity exists worldwide but has been most extensively studied in Western countries, where its prevalence has been estimated to be 0.4% among all children and adults.2 Whether eosinophilic esophagitis is truly a new disease or simply a recently recognized one is uncertain.3 In this review, we consider the diagnostic criteria, pathophysiological and clinical features, and treatment of this increasingly prevalent disease. PMID:26488694

  16. Eosinophilic esophagitis

    PubMed Central

    Merves, Jamie; Muir, Amanda; Chandramouleeswaran, Prasanna Modayur; Cianferoni, Antonella; Wang, Mei-Lun; Spergel, Jonathan M.

    2015-01-01

    Objective To review the understanding of the pathogenesis of eosinophilic esophagitis (EoE) and the role of the immune system in the disease process. Data Sources Peer-reviewed articles on EoE from PubMed searching for “Eosinophilic Esophagitis and fibrosis” in the period of 1995 to 2013. Study Selection Studies on the clinical and immunologic features, pathogenesis, and management of EoE. Results Recent work has revealed that thymic stromal lymphopoietin and basophil have an increased role in the pathogenesis of disease. Additional understanding on the role of fibrosis in EoE is emerging. Conclusion The incidence of EoE is increasing like most atopic disease. Similar to other allergic diseases, EoE is treated with topical steroids and/or allergen avoidance. PMID:24566295

  17. Eosinophil count - absolute

    MedlinePlus

    Eosinophils; Absolute eosinophil count ... the white blood cell count to give the absolute eosinophil count. ... than 500 cells per microliter (cells/mcL). Normal value ranges may vary slightly among different laboratories. Talk ...

  18. Eosinophilic Skin Diseases: A Comprehensive Review.

    PubMed

    Long, Hai; Zhang, Guiying; Wang, Ling; Lu, Qianjin

    2016-04-01

    Eosinophilic skin diseases, commonly termed as eosinophilic dermatoses, refer to a broad spectrum of skin diseases characterized by eosinophil infiltration and/or degranulation in skin lesions, with or without blood eosinophilia. The majority of eosinophilic dermatoses lie in the allergy-related group, including allergic drug eruption, urticaria, allergic contact dermatitis, atopic dermatitis, and eczema. Parasitic infestations, arthropod bites, and autoimmune blistering skin diseases such as bullous pemphigoid, are also common. Besides these, there are several rare types of eosinophilic dermatoses with unknown origin, in which eosinophil infiltration is a central component and affects specific tissue layers or adnexal structures of the skin, such as the dermis, subcutaneous fat, fascia, follicles, and cutaneous vessels. Some typical examples are eosinophilic cellulitis, granuloma faciale, eosinophilic pustular folliculitis, recurrent cutaneous eosinophilic vasculitis, and eosinophilic fasciitis. Although tissue eosinophilia is a common feature shared by these disorders, their clinical and pathological properties differ dramatically. Among these rare entities, eosinophilic pustular folliculitis may be associated with human immunodeficiency virus (HIV) infection or malignancies, and some other diseases, like eosinophilic fasciitis and eosinophilic cellulitis, may be associated with an underlying hematological disorder, while others are considered idiopathic. However, for most of these rare eosinophilic dermatoses, the causes and the pathogenic mechanisms remain largely unknown, and systemic, high-quality clinical investigations are needed for advances in better strategies for clinical diagnosis and treatment. Here, we present a comprehensive review on the etiology, pathogenesis, clinical features, and management of these rare entities, with an emphasis on recent advances and current consensus. PMID:25876839

  19. Expression and subcellular localization of the Qa-SNARE syntaxin17 in human eosinophils

    SciTech Connect

    Carmo, Lívia A.S.; Dias, Felipe F.; Malta, Kássia K.; Amaral, Kátia B.; Shamri, Revital; Weller, Peter F.; Melo, Rossana C.N.

    2015-10-01

    Background: SNARE members mediate membrane fusion during intracellular trafficking underlying innate and adaptive immune responses by different cells. However, little is known about the expression and function of these proteins in human eosinophils, cells involved in allergic, inflammatory and immunoregulatory responses. Here, we investigate the expression and distribution of the Qa-SNARE syntaxin17 (STX17) within human eosinophils isolated from the peripheral blood. Methods: Flow cytometry and a pre-embedding immunonanogold electron microscopy (EM) technique that combines optimal epitope preservation and secondary Fab-fragments of antibodies linked to 1.4 nm gold particles for optimal access to microdomains, were used to investigate STX17. Results: STX17 was detected within unstimulated eosinophils. Immunogold EM revealed STX17 on secretory granules and on granule-derived vesiculotubular transport carriers (Eosinophil Sombrero Vesicles-EoSVs). Quantitative EM analyses showed that 77.7% of the granules were positive for STX17 with a mean±SEM of 3.9±0.2 gold particles/granule. Labeling was present on both granule outer membranes and matrices while EoSVs showed clear membrane-associated labeling. STX17 was also present in secretory granules in eosinophils stimulated with the cytokine tumor necrosis factor alpha (TNF-α) or the CC-chemokine ligand 11 CCL11 (eotaxin-1), stimuli that induce eosinophil degranulation. The number of secretory granules labeled for STX17 was significantly higher in CCL11 compared with the unstimulated group. The level of cell labeling did not change when unstimulated cells were compared with TNF-α-stimulated eosinophils. Conclusions: The present study clearly shows by immunanonogold EM that STX17 is localized in eosinophil secretory granules and transport vesicles and might be involved in the transport of granule-derived cargos. - Highlights: • First demonstration of the Qa-SNARE syntaxin-17 (STX17) in human eosinophils. • High

  20. Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma

    PubMed Central

    Barthel, Steven R.; Johansson, Mats W.; McNamee, Dawn M.; Mosher, Deane F.

    2010-01-01

    Eosinophilic inflammation is a characteristic feature of asthma. Integrins are highly versatile cellular receptors that regulate extravasation of eosinophils from the postcapillary segment of the bronchial circulation to the airway wall and airspace. Such movement into the asthmatic lung is described as a sequential, multistep paradigm, whereby integrins on circulating eosinophils become activated, eosinophils tether in flow and roll on bronchial endothelial cells, integrins on rolling eosinophils become further activated as a result of exposure to cytokines, eosinophils arrest firmly to adhesive ligands on activated endothelium, and eosinophils transmigrate to the airway in response to chemoattractants. Eosinophils express seven integrin heterodimeric adhesion molecules: alpha4beta1 (CD49d/29), alpha6beta1 (CD49f/29), alphaMbeta2 (CD11b/18), alphaLbeta2 (CD11a/18), alphaXbeta2 (CD11c/18), alphaDbeta2 (CD11d/18), and alpha4beta7 (CD49d/beta7). The role of these integrins in eosinophil recruitment has been elucidated by major advances in the understanding of integrin structure, integrin function, and modulators of integrins. Such findings have been facilitated by cellular experiments of eosinophils in vitro, studies of allergic asthma in humans and animal models in vivo, and crystal structures of integrins. Here, we elaborate on how integrins cooperate to mediate eosinophil movement to the asthmatic airway. Antagonists that target integrins or the effectors that regulate integrins of eosinophils represent potentially promising therapies in the treatment of asthma. PMID:17906117

  1. Eosinophilic esophagitis.

    PubMed

    Kedia, Saurabh; Baruah, Bhaskar Jyoti; Makharia, Govind; Ahuja, Vineet

    2015-01-01

    Eosinophilic esophagitis (EoE) is a clinico-pathological entity characterised by symptoms of esophageal dysfunction and eosinophilia on esophageal mucosal biopsies in the absence of other causes of esophageal eosinophilia. It is a chronic inflammatory condition of esophagus often characterized by refractory reflux symptoms in children and dysphagia in adults. It occurs as a result of Th2 inflammatory response to environmental triggers (food antigens) in genetically predisposed individuals. The diagnostic criteria include symptoms of esophageal dysfunction, esophageal eosinophilia (> 15/hpf), and a PPI trial (persistent eosinophilia after 8 weeks of PPI). Mainstay of treatment at present is topical steroids and dietary therapy. Maintenance treatment should be considered to prevent long term complications. PMID:27522734

  2. Eosinophilic Lung Diseases.

    PubMed

    Cottin, Vincent

    2016-09-01

    Eosinophilic lung diseases especially comprise eosinophilic pneumonia or as the more transient Löffler syndrome, which is most often due to parasitic infections. The diagnosis of eosinophilic pneumonia is based on characteristic clinical-imaging features and the demonstration of alveolar eosinophilia, defined as at least 25% eosinophils at BAL. Peripheral blood eosinophilia is common but may be absent at presentation in idiopathic acute eosinophilic pneumonia, which may be misdiagnosed as severe infectious pneumonia. All possible causes of eosinophilia, including drug, toxin, fungus related etiologies, must be thoroughly investigated. Extrathoracic manifestations should raise the suspicion of eosinophilic granulomatosis with polyangiitis. PMID:27514599

  3. Indomethacin inhibits eosinophil migration to prostaglandin D2: therapeutic potential of CRTH2 desensitization for eosinophilic pustular folliculitis

    PubMed Central

    Kataoka, Naoko; Satoh, Takahiro; Hirai, Aiko; Saeki, Kazumi; Yokozeki, Hiroo

    2013-01-01

    Summary Indomethacin is a cyclo-oxygenase inhibitor, and shows therapeutic potential for various eosinophilic skin diseases, particularly eosinophilic pustular folliculitis. One of the unique characteristics of indomethacin is that, unlike other non-steroidal anti-inflammatory drugs, it is a potent agonist of chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a receptor for prostaglandin D2 (PGD2). This study investigated the pharmacological actions of indomethacin on eosinophil migration to clarify the actual mechanisms underlying the therapeutic effects of indomethacin on eosinophilic pustular folliculitis. Eosinophils exhibited chemokinetic and chemotactic responses to both PGD2 and indomethacin through CRTH2 receptors. Pre-treatment of eosinophils with indomethacin greatly inhibited eosinophil migration to PGD2 and, to a much lesser extent, to eotaxin (CCL11); these effects could be mediated by homologous and heterologous desensitization of eosinophil CRTH2 and CCR3, respectively, by agonistic effects of indomethacin on CRTH2. Indomethacin also cancelled a priming effect of Δ12-PGJ2, a plasma metabolite of PGD2, on eosinophil chemotaxis to eotaxin. Indomethacin down-modulated cell surface expression of both CRTH2 and CCR3. Hair follicle epithelium and epidermal keratinocytes around eosinophilic pustules together with the eccrine apparatus of palmoplantar lesions of eosinophilic pustular folliculitis were immunohistochemically positive for lipocalin-type PGD synthase. Indomethacin may exert therapeutic effects against eosinophilic skin diseases in which PGD2-CRTH2 signals play major roles by reducing eosinophil responses to PGD2. PMID:23582181

  4. Eosinophilic Endotype of Asthma.

    PubMed

    Aleman, Fernando; Lim, Hui Fang; Nair, Parameswaran

    2016-08-01

    Asthma is a heterogeneous disease that can be classified into different clinical endotypes, depending on the type of airway inflammation, clinical severity, and response to treatment. This article focuses on the eosinophilic endotype of asthma, which is defined by the central role that eosinophils play in the pathophysiology of the condition. It is characterized by elevated sputum and/or blood eosinophils on at least 2 occasions and by a significant response to treatments that suppress eosinophilia. Histopathologic demonstration of eosinophils in the airways provides the most direct diagnosis of eosinophilic asthma; but it is invasive, thus, impractical in clinical practice. PMID:27401626

  5. Eosinophilic gastroenteritis and related eosinophilic disorders.

    PubMed

    Prussin, Calman

    2014-06-01

    Eosinophilic gastroenteritis (EGE) represents one member within the spectrum of diseases collectively referred to as eosinophilic gastrointestinal disorders, which includes eosinophilic esophagitis (EoE), gastritis, enteritis, and colitis. EGE is less common than EoE and involves a different site of disease but otherwise shares many common features with EoE. The clinical manifestations of EGE are protean and can vary from nausea and vomiting to protein-losing enteropathy or even bowel obstruction requiring surgery. Although systemic corticosteroids are an effective treatment for EGE, their use results in substantial corticosteroid toxicity. Accordingly, there is a great need for improved therapies for these patients. PMID:24813518

  6. Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis

    PubMed Central

    Kim, Ji Heui; Choi, Go Eun; Lee, Bong-Jae; Kwon, Seog Woon; Lee, Seung-Hyo; Kim, Hun Sik; Jang, Yong Ju

    2016-01-01

    Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD2, is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD2 and its metabolite, but not PGE2 and a panel of cytokines including TGF-β, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD2-dependent, rather than PGE2-dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD2, as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS. PMID:27271931

  7. Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis.

    PubMed

    Kim, Ji Heui; Choi, Go Eun; Lee, Bong-Jae; Kwon, Seog Woon; Lee, Seung-Hyo; Kim, Hun Sik; Jang, Yong Ju

    2016-01-01

    Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD2, is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD2 and its metabolite, but not PGE2 and a panel of cytokines including TGF-β, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD2-dependent, rather than PGE2-dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD2, as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS. PMID:27271931

  8. Participation of eosinophils in the toxic oil syndrome.

    PubMed Central

    Ten, R M; Kephart, G M; Posada, M; Abaitua, I; Soldevilla, L; Kilbourne, E M; Dunnette, S L; Gleich, G J

    1990-01-01

    The participation of eosinophils in the Spanish toxic oil syndrome (TOS) was investigated. Eosinophil infiltration and degranulation in tissues from 52 patients with the TOS were examined by immunofluorescence staining for the eosinophil granule major basic protein (MBP). Serum MBP levels were determined in sera from 323 patients. Eosinophil infiltration and degranulation were found in several tissues, especially during the acute phase of the TOS, and serum MBP was significantly elevated during all phases of the disease, suggesting that eosinophils play a role in the pathogenesis of the TOS. Images Fig. 2 Fig. 3 Fig. 4 PMID:2242612

  9. Eosinophils: important players in humoral immunity.

    PubMed

    Berek, C

    2016-01-01

    Eosinophils perform numerous tasks. They are involved in inflammatory reactions associated with innate immune defence against parasitic infections and are also involved in pathological processes in response to allergens. Recently, however, it has become clear that eosinophils also play crucial non-inflammatory roles in the generation and maintenance of adaptive immune responses. Eosinophils, being a major source of the plasma cell survival factor APRIL (activation and proliferation-induced ligand), are essential not only for the long-term survival of plasma cells in the bone marrow, but also for the maintenance of these cells in the lamina propria which underlies the gut epithelium. At steady state under non-inflammatory conditions eosinophils are resident cells of the gastrointestinal tract, although only few are present in the major organized lymphoid tissue of the gut - the Peyer's patches (PP). Surprisingly, however, lack of eosinophils abolishes efficient class-switching of B cells to immunoglobulin (Ig)A in the germinal centres of PP. Thus, eosinophils are required to generate and to maintain mucosal IgA plasma cells, and as a consequence their absence leads to a marked reduction of IgA both in serum and in the gut-associated lymphoid tissues (GALT). Eosinophils thus have an essential part in long-term humoral immune protection, as they are crucial for the longevity of antibody-producing plasma cells in the bone marrow and, in addition, for gut immune homeostasis. PMID:26291602

  10. Human eosinophil transmigration.

    PubMed

    Bazan-Socha, Stanislawa; Zuk, Joanna; Jakiela, Bogdan; Musial, Jacek

    2014-01-01

    In this chapter we describe an optimized eosinophil transmigration assay. Transmigration of purified human peripheral blood eosinophils can be studied using special insert with membrane coated with extracellular matrix components or membrane covered with cells growing as a confluent monolayer, such as vascular endothelial cells of any origin or airway epithelial cells. In our opinion, eosinophil transmigration assay performed through monolayer of human microvascular endothelial cells of lung origin is a suitable tool to estimate the full migratory potential of eosinophils in studies on the pathology of asthma or other respiratory diseases, where eosinophils play important effector functions. This experimental system is easy to perform, simple for optimization, and comparable to in vivo processes occurring during eosinophil migration to the inflammatory sites in lungs. PMID:24986615

  11. Eosinophilic Gastroenteritis : Brief Review.

    PubMed

    Shih, H-M; Bair, M-J; Chen, H-L; Lin, I-T

    2016-01-01

    Eosinophilic gastroenteritis (EGE) is a rare disease which belongs to primary eosinophilic gastrointestinal disorders (primary EGIDs), characterized by an accumulation of eosinophils in the gastrointestinal (GI) tract and is strongly associated with atopy and allergy. The clinical presentations vary depending on the site and depth of eosinophilic intestinal infiltration. Radiology pictures may show irregular thickening of the folds, but these findings can also be present in other conditions like inflammatory bowel disease and lymphoma. The endoscopic appearance is also nonspecific. The definite diagnosis requires biopsy for histological evidence of GI eosinophilic infiltration and clinicians make the diagnosis in correlation with and by exclusion of other possible causes of eosinophilic infiltration. Because EGE is a rare disease, the treatment is based on limited case reports and clinicians' experience. Corticosteroids are the mainstay of therapy. The prognosis of EGE is relatively good when patients receive timely and proper treatment. PMID:27382945

  12. Eosinophilic gastroenteritis and related eosinophilic disorders

    PubMed Central

    Prussin, Calman

    2014-01-01

    Eosinophilic gastroenteritis (EGE) represents one member within the spectrum of diseases collectively referred to as eosinophilic gastrointestinal disorders (EGIDs), which includes eosinophilic esophagitis (EoE), gastritis, enteritis, and colitis. EGE is less common than EoE and involves a different site of disease, but otherwise shares many common features with EoE. The clinical manifestations of EGE are protean and can vary from nausea and vomiting to protein losing enteropathy or even bowel obstruction requiring surgery. Although systemic corticosteroids are an effective treatment for EGE, their use over the chronic course of the disease results in substantial corticosteroid toxicity. Accordingly, there is a great need for improved therapies for these patients. PMID:24813518

  13. [Angiostrongylosis or eosinophilic meningitis].

    PubMed

    Bourée, Patrice; Dumazedier, Déborah; Dahane, Naïma

    2010-04-20

    Eosinophilic meningitis, or angiostrongyliasis, is a common disease in Asia, in the Caribbean and in the Pacific islands. It is caused by a rat lungworm Angiostrongylus cantonensis. Infection occurs by consumption of raw or undercooked snails. Diagnosis is based on epidemiological criteria, clinical manifestations, elevated count of eosinophils in the cerebrospinal fluid and serological tests. Treatment is symptomatic and supportive. PMID:20465114

  14. Bone Marrow Derived Eosinophil Cultures

    PubMed Central

    Lu, Thomas X.; Rothenberg, Marc E.

    2016-01-01

    Eosinophils are multifunctional effector cells implicated in the pathogenesis of a variety of diseases including asthma, eosinophil gastrointestinal disorders and helminth infection. Mouse bone marrow derived progenitor cells can be differentiated into eosinophils following IL-5 exposure. These bone marrow derived eosinophils are fully differentiated at the end of a 14 day culture based on morphology and expression of molecular markers.

  15. Pseudotumoral Eosinophilic Cystitis

    PubMed Central

    Saadi, Ahmed; Bouzouita, Abderrazak; Ayed, Haroun; Kerkeni, Walid; Cherif, Mohamed; Ben Slama, Riadh M.; Derouiche, Amine; Chebil, Mohamed

    2015-01-01

    Eosinophilic cystitis is a rare inflammatory disease of the bladder which origin and pathogenesis are unknown. Since the first description in 1960, hundreds of cases have been reported, 20 Pseudotumor forms. We report a case of cystitis eosinophils in tumor-form, a patient of 72 years without urological or allergic history. The patient was treated with endoscopic resection alone. The outcome was favorable with disappearance symptoms and no recurrence at 1, 3 and 6 months controls. We carry a literature review of cystitis eosinophils on the different clinical manifestations, the means diagnostic and therapeutic modalities. PMID:26793503

  16. [Eosinophilic cellulitis (Wells' syndrome)].

    PubMed

    Cerri, D; Carabelli, A; Bertani, E; Portaluppi, F; Novi, C; Gianotti, R; Gelmetti, C

    1990-09-01

    The Authors report a case of eosinophilic cellulitis (Wells' syndrome). The patient was a 61 year old woman, diabetic, with a cardio-respiratory insufficiency and a maniaco-depressive psycosis. She presented, on the upper arms and trunk, a cutaneous eruption of erythematous-urticarial plaques, that histopathologically were characterized by a dermic leukocyte population, with a prevalence of eosinophils, distributed in the perivascular site. Laboratory tests revealed eosinophilia and circulating immune complexes. The etiopathogenesis of the disease is discussed as is the possible role of immune complexes in eosinophilic cellulitis. PMID:2079351

  17. Properties of lightweight aggregate concrete prepared with PVC granules derived from scraped PVC pipes.

    PubMed

    Kou, S C; Lee, G; Poon, C S; Lai, W L

    2009-02-01

    This paper aims to investigate the fresh and hardened properties of lightweight aggregate concretes that are prepared with the use of recycled plastic waste sourced from scraped PVC pipes to replace river sand as fine aggregates. A number of laboratory prepared concrete mixes were tested, in which river sand was partially replaced by PVC plastic waste granules in percentages of 0%, 5%, 15%, 30% and 45% by volume. Two major findings are identified. The positive side shows that the concrete prepared with a partial replacement by PVC was lighter (lower density), was more ductile (greater Poisson's ratios and reduced modulus of elasticity), and had lower drying shrinkage and higher resistance to chloride ion penetration. The negative side reveals that the workability, compressive strength and tensile splitting strength of the concretes were reduced. The results gathered would form a part of useful information for recycling PVC plastic waste in lightweight concrete mixes. PMID:18691863

  18. Eosinophilic cellulitis and dermographism.

    PubMed

    Nguyen, Nathalie Q; Ma, Linglei

    2005-01-01

    A 26-year-old man presented with a history of intermittent erythematous plaques on his hands and legs. A peripheral blood eosinophilia was noted. Histopathologic examination showed numerous eosinophils and characteristic flame figures. The clinical presentation and histopathologic alterations are consistent with the diagnosis of Wells' syndrome, which is also known as eosinophilic cellulitis. Wells' syndrome is a rare condition of unclear etiology. We discuss its diagnosis and possible association with other conditions that manifest peripheral eosinophilia. PMID:16403379

  19. The Eosinophil in Infection.

    PubMed

    Ravin, Karen A; Loy, Michael

    2016-04-01

    First described by Paul Ehrlich in 1879, who noted its characteristic staining by acidophilic dyes, for many years, the eosinophil was considered to be an end-effector cell associated with helminth infections and a cause of tissue damage. Over the past 30 years, research has helped to elucidate the complexity of the eosinophil's function and establish its role in host defense and immunity. Eosinophils express an array of ligand receptors which play a role in cell growth, adhesion, chemotaxis, degranulation, and cell-to-cell interactions. They play a role in activation of complement via both classical and alternative pathways. Eosinophils synthesize, store and secrete cytokines, chemokines, and growth factors. They can process antigen, stimulate T cells, and promote humoral responses by interacting with B cells. Eosinophils can function as antigen presenting cells and can regulate processes associated with both T1 and T2 immunity. Although long known to play a role in defense against helminth organisms, the interactions of eosinophils with these parasites are now recognized to be much more complex. In addition, their interaction with other pathogens continues to be investigated. In this paper, we review the eosinophil's unique biology and structure, including its characteristic granules and the effects of its proteins, our developing understanding of its role in innate and adaptive immunity and importance in immunomodulation, and the part it plays in defense against parasitic, viral, fungal and bacterial infections. Rather than our worst enemy, the eosinophil may, in fact, be one of the most essential components in host defense and immunity. PMID:26690368

  20. Chronic eosinophilic pneumonia.

    PubMed Central

    Fox, B; Seed, W A

    1980-01-01

    We described three cases of eosinophilic pneumonia of unknown aetiology investigated clinically and by lung biopsy. The illnesses lasted between six and 20 weeks and consisted of cough, dyspnoea, malaise, and in two cases prolonged pyrexia. All had blood eosinophilia and chest radiographs showing widespread bilateral shadowing; in two cases this had a characteristic peripheral distribution. One patient recovered spontaneously and the other two responded to steroids, with disappearance of pyrexia within 12 hours and radiological clearing within 14 days. Lung function tests during the acute illness showed volume restriction or gas transfer defects or both in two cases. After remission all three showed abnormalities if small airways function. Lung biopsies performed during the acute illness were examined histologically and by transmission electron microscopy, and in two cases by immunofluorescence. There was both intra-alveolar and interstitial eosinophilic pneumonia with bronchiolitis obliterans, microgranulomata, and a vasculitis. Electron microscopy showed numerous eosinophils, many degranulated, and macrophages with phagocytosed eosinophilic granules and intracytoplasmic inclusions. In one case IgM, IgG, and IgA were demonstrated in the bronchial walls and interstitium. No IgE or complement was present. We believe that eosinophil granules are responsible for the tissue damage and fever and suggest mechanisms for this and for the response to steroid therapy. Images PMID:7003796

  1. Eosinophilic granuloma of the ileum

    PubMed Central

    Myers, A.; Humphreys, Daphne M.; Williamson, R. C. N.

    1975-01-01

    A case of eosinophilic granuloma of the ileum is described in association with a high (50%) eosinophil count. A review of published suggested classifications, aetiology and therapy is made. ImagesFig. 2Fig. 3 PMID:1114154

  2. Eosinophilic Liver Infiltration

    PubMed Central

    Figueroa Rivera, Ivonne; Toro, Doris H.; Gutierrez, Jose; Acosta, Eduardo

    2015-01-01

    Eosinophilic liver infiltration is a commonly encountered focal eosinophil-related inflammation with or without necrosis, which can be seen on computed tomography (CT) in the presence of peripheral eosinophilia. Although this entity has a relatively benign course, it is related to numerable conditions for which diagnosis may be challenging and requires substantial diagnostic work-up for proper management and care of the underlying disease. We report a case of a 60-year-old man who presented with a 1-week history of right upper quadrant abdominal pain with multiple ill-defined liver hypodensities associated with significant eosinophilia. PMID:26504883

  3. 2013 Update on Celiac Disease and Eosinophilic Esophagitis

    PubMed Central

    Pellicano, Rinaldo; De Angelis, Claudio; Ribaldone, Davide Giuseppe; Fagoonee, Sharmila; Astegiano, Marco

    2013-01-01

    Celiac disease is a chronic, immune-mediated disorder, characterized by small intestinal inflammation and villous atrophy after the ingestion of gluten by genetically susceptible individuals. Several extraintestinal manifestations have been associated to celiac disease. Eosinophilic esophagitis is a primary disorder of the esophagus characterized by upper gastrointestinal symptoms, absence of gastroesophageal reflux disease and more than 15 eosinophils per high-power field in biopsy specimens. Both celiac disease and eosinophilic esophagitis are caused by aberrant, but distinct, immune responses to ingested antigens and can be responsive to restricted food intake. The aim of this review is to assess whether there is an association between these two pathologies. In the majority of the studies examined, including the studies in pediatric population, the prevalence of eosinophilic esophagitis in subjects with celiac disease was about 10-times that of the general population. We suggest searching for eosinophilic esophagitis in all children undergoing endoscopy for suspicious celiac disease. PMID:23974065

  4. Eosinophilic Drug Allergy.

    PubMed

    Kuruvilla, Merin; Khan, David A

    2016-04-01

    While peripheral or tissue eosinophilia may certainly characterize drug eruptions, this feature is hardly pathognomonic for a medication-induced etiology. While delayed drug hypersensitivity reactions with prominent eosinophilic recruitment have been typically classified as type IVb reactions, their pathophysiology is now known to be more complex. Eosinophilic drug reactions have a diversity of presentations and may be benign and self-limited to severe and life-threatening. The extent of clinical involvement is also heterogeneous, ranging from isolated peripheral eosinophilia or single organ involvement (most often the skin and lung) to systemic disease affecting multiple organs, classically exemplified by drug-reaction with eosinophilia and systemic symptoms (DRESS). The spectrum of implicated medications in the causation of DRESS is ever expanding, and multiple factors including drug metabolites, specific HLA alleles, herpes viruses, and immune system activation have been implicated in pathogenesis. Due to this complex interplay of various factors, diagnostic workup in terms of skin and laboratory testing has not been validated. Similarly, the lack of controlled trials limits treatment options. This review also describes other localized as well as systemic manifestations of eosinophilic disease induced by various medication classes, including their individual pathophysiology, diagnosis, and management. Given the multitude of clinical patterns associated with eosinophilic drug allergy, the diagnosis can be challenging. Considerable deficits in our knowledge of these presentations remain, but the potential for severe reactions should be borne in mind in order to facilitate diagnosis and institute appropriate management. PMID:26006718

  5. Eosinophilic Esophagitis and Gastroenteritis.

    PubMed

    Cianferoni, Antonella; Spergel, Jonathan M

    2015-09-01

    Eosinophilic gastrointestinal disease (EGID) can be classified as eosinophilic esophagitis (EoE) when the eosinophilia is limited to the esophagus or as eosinophilic gastritis (EG) if it is limited to the gastric tract, eosinophilic colitis (EC) if it is limited to the colon, and eosinophilic gastroenteritis (EGE) if the eosinophilia involves one or more parts of the gastrointestinal tract. EoE is by far the most common EGID. It is a well-defined chronic atopic disease due to a T helper type 2 (Th2) inflammation triggered often by food allergens. EoE diagnosis is done if an esophageal biopsy shows at least 15 eosinophils per high power field (eos/hpf). Globally accepted long-term therapies for EoE are the use of swallowed inhaled steroids or food antigen avoidance. The treatment of EoE is done not only to control symptoms but also to prevent complications such as esophageal stricture and food impaction. EGE cause non-specific gastrointestinal (GI) symptoms and are diagnosed if esophagogastroduodenoscopy (EGD)/colonoscopy show eosinophilia in one or more parts of the GI tract. They are rare diseases with an unclear pathogenesis, and they are poorly defined in terms of diagnostic criteria and treatment. Before initiating treatment of any EGE, it is imperative to conduct a differential diagnosis to exclude other causes of hypereosinophilia with GI localization. EGE are often poorly responsive to therapy and there is no commonly accepted long-term treatment. EG has many characteristics similar to EoE, including the fact that it is often due to a food allergen-driven Th2 inflammation; transcriptome analysis however shows that it is more a systemic disease and has a different gene signature than EoE. EC is a benign form of delayed food allergy in infant and is instead a difficult-to-treat severe inflammatory condition in older children and adults. EC in the latter groups can be a manifestation of drug allergy or autoimmune disease. Overall EGE, EC, and EG are rare and

  6. Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

    PubMed Central

    Cadman, Emma T.; Thysse, Katherine A.; Bearder, Siobhan; Cheung, Anita Y. N.; Johnston, Ashleigh C.; Lee, James J.; Lawrence, Rachel A.

    2014-01-01

    Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity. PMID:24626328

  7. Eosinophil granule cationic proteins regulate the classical pathway of complement.

    PubMed Central

    Weiler, J M; Edens, R E; Bell, C S; Gleich, G J

    1995-01-01

    Major basic protein, the primary constituent of eosinophil granules, regulates the alternative and classical pathways of complement. Major basic protein and other eosinophil granule cationic proteins, which are important in mediating tissue damage in allergic disease, regulate the alternative pathway by interfering with C3b interaction with factor B to assemble an alternative pathway C3 convertase. In the present study, eosinophil peroxidase, eosinophil cationic protein and eosinophil-derived neurotoxin, as well as major basic protein, were examined for capacity to regulate the classical pathway. Eosinophil peroxidase, eosinophil cationic protein and major basic protein inhibited formation of cell-bound classical pathway C3 convertase (EAC1,4b,2a), causing 50% inhibition of complement-mediated lysis at about 0.19, 0.75 and 0.5 micrograms/10(7) cellular intermediates, respectively. Eosinophil-derived neurotoxin had no activity on this pathway of complement. The eosinophil granule proteins were examined for activity on the formation of the membrane attack complex. Major basic protein and eosinophil cationic protein had no activity on terminal lysis. In contrast, eosinophil peroxidase inhibited lysis of EAC1,4b,2a,3b,5b, but had only minimal activity on later events in complement lysis. These polycations were then examined to determine the site(s) at which they regulated the early classical pathway. Eosinophil granule polycationic proteins: (1) reduced the Zmax at all time points but had only minimal effect on the Tmax during the formation of the classical pathway C3 convertase (EAC1,4b,2a); (2) inhibited formation of EAC1,4b,2a proportional to C4 but independent of C2 concentration; (3) inhibited fluid phase formation of C1,4b,2a, as reflected by a decrease in C1-induced consumption of C2 over time; and (4) inhibited C1 activity over time without a direct effect on either C4 or C2. These observations suggest that polycations regulate the early classical pathway by

  8. Chronic eosinophilic pancreatitis and ulcerative colitis in a horse.

    PubMed

    Breider, M A; Kiely, R G; Edwards, J F

    1985-04-15

    A generalized debilitating disease in a horse was believed to be related to hypersensitivity to migrating strongyle larvae. The clinical signs included weight loss, diarrhea, and ulcers on all 4 coronary bands. The mare's condition deteriorated rapidly, so the mare was euthanatized and necropsied. The major histopathologic findings were chronic multifocal eosinophilic pancreatitis, hepatic portal fibrosis, biliary hyperplasia, and chronic ulcerative eosinophilic colitis. This case was similar to previously reported cases of chronic eosinophilic gastroenteritis in horses. Although the etiologic agent was not evident, the distribution and character of the lesions were consistent with a hypersensitivity response to migrating parasitic larvae, most probably Strongylus equinus. PMID:3997643

  9. Eosinophilic bioactivities in severe asthma.

    PubMed

    Carr, Tara F; Berdnikovs, Sergejs; Simon, Hans-Uwe; Bochner, Bruce S; Rosenwasser, Lanny J

    2016-01-01

    Asthma is clearly related to airway or blood eosinophilia, and asthmatics with significant eosinophilia are at higher risk for more severe disease. Eosinophils actively contribute to innate and adaptive immune responses and inflammatory cascades through the production and release of diverse chemokines, cytokines, lipid mediators and other growth factors. Eosinophils may persist in the blood and airways despite guidelines-based treatment. This review details eosinophil effector mechanisms, surface markers, and clinical outcomes associated with eosinophilia and asthma severity. There is interest in the potential of eosinophils or their products to predict treatment response with biotherapeutics and their usefulness as biomarkers. This is important as monoclonal antibodies are targeting cytokines and eosinophils in different lung environments for treating severe asthma. Identifying disease state-specific eosinophil biomarkers would help to refine these strategies and choose likely responders to biotherapeutics. PMID:27386041

  10. Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs

    PubMed Central

    Varricchi, Gilda; Bagnasco, Diego; Borriello, Francesco; Heffler, Enrico; Canonica, Giorgio W.

    2016-01-01

    Purpose of review Human eosinophils were first identified and named by Paul Ehrlich in 1879 on the basis of the cell's granular uptake of eosin. Although eosinophils represent approximately 1% of peripheral blood leukocytes, they have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophils and their mediators are critical effectors to asthma and eosinophilic granulomatosis with polyangiitis (EGPA). Eosinophils are equipped with a large number of cell-surface receptors and produce specific cytokines and chemokines. Recent findings Eosinophils are the major source of interleukin-5 and highly express the interleukin-5Rα on their surface. Clinical trials evaluating monoclonal antibodies to interleukin-5 (mepolizumab and reslizumab) and its receptor interleukin-5Rα (benralizumab) have been or are underway in patients with eosinophilic asthma, EGPA and chronic obstructive pulmonary disease (COPD). Overall, targeting interleukin-5/interleukin-5Rα is associated with a marked decrease in blood and sputum eosinophilia, the number of exacerbations and improvement of some clinical parameters in adult patients with severe eosinophilic asthma. Pilot studies suggest that mepolizumab might be a glucocorticoid-sparing treatment in patients with EGPA. A preliminary study found that benralizumab did not reduce the exacerbations and did modify lung function in patients with eosinophilic COPD. Summary The review examines recent advances in the biology of eosinophils and how targeting the interleukin-5 pathway might offer benefit to some patients with severe asthma, EGPA, and COPD. Interleukin-5/interleukin-5Rα-targeted treatments offer promises to patients with eosinophilic respiratory disorders. PMID:26859368

  11. An improved method to visualize eosinophils in eosinophilic esophagitis.

    PubMed

    Rubio, C A; Glaessgen, A

    2006-01-01

    We previously found in Giemsa-stained colorectal sections from IBD patients that eosinophilic granulocytes turned fluorescent when excited with indirect fluorescent light, while other inflammatory cells were non-fluorescent. We now studied with that method, the frequency of eosinophilic granulocytes in sections from patients with eosinophilic esophagitis (EE). Cell counting was done in consecutive sections stained with Giemsa stain using indirect fluorescence light (G-IFL setting) and with hematoxylin-eosin using transmitted light (HE-TL setting) in 5 cases of EE and in 10 consecutive cases of reflux esophagitis (RE) grade 2. In EE 45.0 eosinophils/case (range 39-51) were recorded with the G-IFL setting but only 33.4 eosinophils/case (range 28-39) with the HE-TL setting (p < 0.05). In RE cases, 3 eosinophils/case (range 2-4) were found with the G-IFL setting and 2 eosinophil/case (range 1-3) with the HE-TL setting. The G-IFL method is not only more sensitive in detecting eosinophils than the conventional HE-TL method but also quicker, since a differential cell counting is not necessary. PMID:17091778

  12. Eosinophilic Cystitis with Eosinophilic Cholecystitis: A Rare Association

    PubMed Central

    Mallat, F.; Hmida, W.; Mestiri, S.; Ziadi, S.; Sriha, B.; Mokni, M.; Mosbah, F.

    2013-01-01

    We describe a rare case of eosinophilic cystitis associated with eosinophilic cholecystitis in a 30-year-old patient who underwent bladder biopsy for irritative voiding symptoms and routine elective cholecystectomy for gallstones. Diagnosis was confirmed by histopathological examination. The rarity of this condition prompted us to report this entity in which no specific cause could be found. PMID:24195001

  13. Novel Therapies for Eosinophilic Disorders

    PubMed Central

    Bochner, Bruce S.

    2015-01-01

    Synopsis Current therapies for eosinophilic disorders are limited. Most treatment approaches remain empirical, are not supported by data from controlled clinical trials, involve the off-label use of agents developed for treatment of other diseases, and tend to rely heavily on the use of glucocorticoids and other agents with significant toxicity. Also lacking are validated outcome metrics and clinically relevant biomarkers to help guide treatment choices, efficacy and assessment of disease activity. Over the last decade, great progress has been made in the discovery, preclinical development and clinical testing of a variety of biologics and small molecules that have the potential to directly or indirectly influence eosinophils, eosinophilic inflammation and the consequences of eosinophil activation. Particularly advanced are studies with biologics that target eosinophil-selective cytokines and their receptors. In addition, other therapies that have received FDA approval in recent years for non-eosinophil-related indications can be considered for testing in eosinophilic disorders. Overall, the landscape of therapeutic options for those suffering from eosinophilic disorders has never been brighter, with many new choices on the horizon. PMID:26209901

  14. [Eosinophilic esophagitis: an "emerging disease"].

    PubMed

    Collardeau-Frachon, Sophie; Hervieu, Valérie; Scoazec, Jean-Yves

    2007-12-01

    Eosinophilic esophagitis is a recently identified disease. The histological examination of esophageal biopsies is essential for its diagnosis, which is made with steadily increasing frequency. Eosinophilic esophagitis is an anatomoclinical entity, involving both children and adults, characterized by a dense and isolated infiltration of the esophageal mucosa by eosinophils, revealed by clinical symptoms of upper digestive tract origin and resistant to anti-acid treatment with IPP at high doses. Eosinophilic esophagitis is currently interpreted as an allergic disease, even though its pathogenesis remains unclear. The disease has a chronic course with persistent or relapsing symptoms, present with symptoms similar to those of gastro-esophageal reflux or with dysphagia. Endoscopic examination shows the presence of characteristic, but not pathognomonic, lesions (stenoses, strictures, circular rings, reduction of calibre, white specks, granularity of the mucosa). The histological diagnosis requires multiple biopsies taken all along the esophagus. The main sign is the presence of a dense eosinophilic infiltrate of the mucosa: a peak density of more than 15 eosinophils in at least one x400 field is the minimal criteria required for diagnosis. Associated lesions correspond to tissue damage and repair secondary to eosinophil activation (basal hyperplasia, microabscesses, fibrosis of the lamina propria). The treatment is based on dietary measures (allergen exclusion) and on the use of anti-inflammatory drugs, mainly corticoids. In conclusion, eosinophilic esophagitis is an emerging disease, important to identify, since it requires a specific treatment, different from that of reflux esophagitis. PMID:18554551

  15. Eosinophilic Inflammation in Allergic Asthma

    PubMed Central

    Possa, Samantha S.; Leick, Edna A.; Prado, Carla M.; Martins, Mílton A.; Tibério, Iolanda F. L. C.

    2013-01-01

    Eosinophils are circulating granulocytes involved in pathogenesis of asthma. A cascade of processes directed by Th2 cytokine producing T-cells influence the recruitment of eosinophils into the lungs. Furthermore, multiple elements including interleukin (IL)-5, IL-13, chemoattractants such as eotaxin, Clara cells, and CC chemokine receptor (CCR)3 are already directly involved in recruiting eosinophils to the lung during allergic inflammation. Once recruited, eosinophils participate in the modulation of immune response, induction of airway hyperresponsiveness and remodeling, characteristic features of asthma. Various types of promising treatments for reducing asthmatic response are related to reduction in eosinophil counts both in human and experimental models of pulmonary allergic inflammation, showing that the recruitment of these cells really plays an important role in the pathophysiology of allergic diseases such asthma. PMID:23616768

  16. Eosinophil peroxidase-dependent hydroxyl radical generation by human eosinophils.

    PubMed

    McCormick, M L; Roeder, T L; Railsback, M A; Britigan, B E

    1994-11-11

    Eosinophil production of superoxide (O2-.) and hydrogen peroxide (H2O2) is important in host defense. The present study assessed the potential of eosinophils to generate another potent cytotoxic species, the hydroxyl radical (.OH). .OH formation by phorbol myristate acetate (PMA)-stimulated eosinophils was demonstrated using an alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone/ethanol spin trapping system. Additionally, .OH was spin trapped following the addition of purified eosinophil peroxidase (EPO) to a cell-free O2-./H2O2 generating systems. Effects of superoxide dismutase, catalase, azide, aminotriazole, chloride-depleted buffer, and extensive metal chelation were consistent with .OH formation via the reaction of O2-. and EPO-generated hypohalous acid. Under chloride-depleted conditions, physiologic concentrations of Br- increased .OH formation by both PMA-stimulated eosinophils and the cell-free EPO system. Physiologic concentrations of SCN-, however, did not increase .OH formation, and in the presence of both Br- and SCN-, .OH formation was similar to SCN- only. Eosinophils appear to form .OH via an EPO-dependent mechanism, the magnitude of which varies with the availability of various EPO substrates. Given the highly reactive nature of this radical and the ability of EPO to adhere to cell membranes, even small amounts of .OH formed at such sites could contribute to eosinophil-mediated cytotoxicity. PMID:7961724

  17. Angiostrongylus cantonensis eosinophilic meningitis.

    PubMed

    Pien, F D; Pien, B C

    1999-01-01

    In the past 50 years, Angiostrongylus cantonensis, the most common cause of eosinophilic meningitis, has spread from Southeast Asia to the South Pacific, Africa, India, the Caribbean, and recently, to Australia and North America, mainly carried by cargo ship rats. Humans are accidental, "dead-end" hosts infected by eating larvae from snails, slugs, or contaminated, uncooked vegetables. These larvae migrate to the brain, spinal cord, and nerve roots, causing eosinophilia in both spinal fluid and peripheral blood. Infected patients present with severe headache, vomiting, paresthesias, weakness, and occasionally visual disturbances and extraocular muscular paralysis. Most patients have a full recovery; however, heavy infections can lead to chronic, disabling disease and even death. There is no proven treatment for this disease. In the authors' experience, corticosteroids have been helpful in severe cases to relieve intracranial pressure as well as neurologic symptoms due to inflammatory responses to migrating and eventually dying worms. PMID:10460929

  18. Computed tomographic findings in 15 dogs with eosinophilic bronchopneumopathy.

    PubMed

    Mesquita, Luis; Lam, Richard; Lamb, Christopher R; McConnell, J Fraser

    2015-01-01

    Eosinophilic bronchopneumopathy is a disease characterized by the infiltration of the lung and bronchial mucosa by eosinophils. The aim of the present study was to describe the CT findings in a large series of dogs with confirmed diagnosis of eosinophilic bronchopneumopathy. Computed tomographic scans of 15 dogs with confirmed diagnosis of eosinophilic bronchopneumopathy were evaluated retrospectively by two boarded radiologists who reached a consensus. Abnormalities were identified in 14/15 (93%) dogs, including pulmonary parenchymal abnormalities in 14/15 (93%) dogs, bronchial wall thickening in 13 (87%) dogs, which was considered marked in eight (53%), plugging of the bronchial lumen by mucus/debris in 11 (73%) dogs, and bronchiectasis in nine (60%) dogs. Pulmonary nodules were identified in 5/15 (33%) dogs including one dog with a mass. All dogs with a nodular lung pattern had additional abnormalities. Lymphadenopathy was present in 10 dogs (67%). Lesions associated with eosinophilic bronchopneumopathy are variable and heterogeneous and encompass a wider variety of computed tomographic features than reported previously. Computed tomographic images were abnormal in the majority of affected dogs, hence CT is a useful modality to characterize the nature and distribution of thoracic lesions in dogs with eosinophilic bronchopneumopathy. PMID:25124052

  19. Eosinophilic ascites: A case report and literature review

    PubMed Central

    Alsulaiman, Raed M.

    2015-01-01

    Eosinophilic gastroenteritis is a rare gastrointestinal (GI) disorder characterized by nonspecific GI symptoms, peripheral eosinophilia, and eosinophilic infiltration of the intestinal wall. The disorder is classified into mucosal, muscular, and sub-serosal types, depending on the clinical picture and the depth of eosinophilic infiltration within the GI wall. Sub-serosal disease, which is complicated by ascites, usually results in the most severe clinical form of eosinophilic gastroenteritis and requires early corticosteroid therapy. In such cases, a favorable outcome can be achieved after a short course of corticosteroids. We present the case of a 28-year-old female with diffuse abdominal pain and distention for 2 weeks. Her physical examination was significant for moderate ascites. Initial work-up demonstrated severe peripheral blood eosinophilia, normal liver function tests, and elevated serum immunoglobulin E (IgE). Upper endoscopy, colonoscopy showed a thickening of the stomach and colon, and biopsies showed marked eosinophilic infiltration of the mucosa. Ascitic fluid analysis showed significant eosinophilia. Subsequent treatment with oral prednisone resulted in the normalization of laboratory and radiologic abnormalities 45 days after the start of the treatment. Despite its rarity, eosinophilic gastroenteritis needs to be recognized by the clinician because the disease is treatable, and timely diagnosis and initiation of treatment could be of major importance. PMID:26392801

  20. Eosinophilic ascites: a diagnostic challenge.

    PubMed

    Khalil, Hesham; Joseph, Moby

    2016-01-01

    Eosinophilic ascites is a rare feature of eosinophilic gastroenteritis. We would like to highlight this increasingly recognised diagnosis in a case of unexplained ascites. We present a challenging case of a woman aged 25 years who presented with nausea, vomiting, diarrhoea, generalised abdominal pain and swelling 8-week following delivery of her first baby. Her symptoms were primarily aggravated by eating, and she had also noticed postprandial itching and self-limiting generalised rash. She had a strong history of atopy. Physical examination revealed abdominal tenderness and distension with shifting dullness. Urticarial skin rash was noted on the face, neck, chest and abdomen. Routine biochemistry was normal apart from peripheral eosinophilia. Imaging confirmed moderate ascites. Diagnostic paracentesis showed exudative ascites with numerous eosinophils. Histology of the upper and lower gastrointestinal tract showed infiltration of the oesophageogastroduodenal and rectosigmoid mucosa with eosinophils. The patient significantly improved following a course of steroids and six-food elimination diet. PMID:27600059

  1. Eosinophilic Esophagitis: Biology to Therapy

    PubMed Central

    Rothenberg, Marc E.

    2014-01-01

    Eosinophilic esophagitis, a recently recognized and growing clinical disorder over the past decade, is characterized by antigen-driven eosinophil accumulation in the esophagus. Symptoms frequently mimic those of gastroesophageal reflux disease (GERD) but the two diseases are quite distinct in terms of their histopathology, genetic signature, response to therapy, hereditary risk and association with allergy. Disease pathogenesis involves the interplay of external and genetic factors, particularly food antigens and the eosinophil chemoattractant eotaxin-3, respectively. Transcript signatures and animal models have uncovered the importance of adaptive T cell immunity involving IL-5 and IL-13 elicited esophageal epithelial cell responses. Notably, symptoms, dysregulated esophageal gene expression and pathology are largely reversible following reduction of specific food antigen exposure, as well as anti-inflammatory therapy, but chronic treatment is necessary to prevent relapse. As such, eosinophilic esophagitis is a disease with the unique features of chronic esophagitis, atopy, immune sensitization to oral antigens, reversibility and familial association. PMID:19596009

  2. Killing of juvenile Fasciola hepatica by purified bovine eosinophil proteins.

    PubMed Central

    Duffus, W P; Thorne, K; Oliver, R

    1980-01-01

    Eosinophils were isolated from the mammary gland of Fasciola hepatica-infected cattle by intramammary infusion with a crude extract from adult F. hepatica. Up to 5 x 10(9) eosinophils with a purity of over 90% could be obtained from a single quarter of the gland. The major contaminating cells were monocytes which reached their peak several days following the eosinophil peak. Two major proteins were isolated from bovine eosinophil granules, a high molecular weight peroxidase-active protein and a smaller molecular weight predominantly basic protein. This smaller protein was thought to be the bovine equivalent of guinea-pig and human major basic protein (MBP), although it possessed an unusually high concentration of cysteine. The bovine MBP had a profound effect on juvenile F. hepatica in vitro causing damage and death at concentrations down to 1 x 10(-6) M. The damage was detected by a 51Cr release assay and/or a viability assay involving microscopical examination of the flukes. Other cations, especially protamine sulphate, were also shown to kill flukes, although both lysozyme, found in neutrophils, and the peroxidase-positive peak from bovine eosinophils were unable to mediate any detectable damage. Images Fig. 4 PMID:7438542

  3. Olanzapine-induced eosinophilic pleuritis.

    PubMed

    Evison, Matthew; Holme, Jayne; Alaloul, Mohamed; Doran, Helen; Bishop, Paul; Booton, Richard; Chaudhry, Nauman

    2015-01-01

    An elderly patient, with a history of depression with psychosis, presented with breathlessness, a right exudative pleural effusion and a peripheral eosinophilia. The pleural fluid was eosinophil-rich (10% of leucocytes). Olanzapine therapy had been commenced 12 months previously. There was a family history of TB and the patient was of African origin. A full diagnostic work-up ensued including computed tomography of the thorax and local anaesthetic thoracoscopy. The pleura was unremarkable on CT and displayed bland smooth thickening at visual inspection during thoracoscopy. Pleural biopsies demonstrated chronic inflammation with eosinophils but no evidence of granulomatous inflammation or malignancy. Pleural tissue culture did not yield mycobacteria. A diagnosis of olanzapine-induced eosinophilic pleuritis was suspected and the pleural disease resolved with withdrawal of olanzapine. Eosinophilic pleural fluid is not a marker of non-malignant aetiology and eosinophilic pleural effusions require a careful and systematic diagnostic work-up. This is the second case report to identify olanzapine as a causative agent in eosinophilic pleural effusion. PMID:26029571

  4. Eosinophils in the 1990s: new perspectives on their role in health and disease.

    PubMed Central

    Wardlaw, A. J.

    1994-01-01

    Eosinophils are characterized by their unique crystalloid granules that contain four basic proteins--MBP, ECP, EDN and EPO. The cell has many common features with neutrophils but, unlike that cell type, eosinophils utilize VLA-4/VCAM-1 as an adherence pathway and have a number of other receptors not shared by neutrophils. These include recognition units for IgE (distinct from CD23), and receptors for IL-5, IL-3 and RANTES. Following stimulation with a variety of agents, eosinophils preferentially elaborate LTC4 as the major 5-lipoxygenase product of arachidonic acid and produce substantial amounts of PAF. Of particular interest is the ability of eosinophils to synthesize a number of cytokines. Thus eosinophils have marked pro-inflammatory potential. There is now convincing evidence that eosinophilia is T-cell dependent. The Th2-type cell, which selectively secretes IL-5 and IL-4, seems particularly involved. IL-5, IL-3 and GM-CSF are required for eosinophil maturation, and cause activation and prolonged survival of the mature cell. IL-5 is unique in that it promotes terminal differentiation of the committed eosinophil precursor and in vivo in mice appears to be sufficient on its own for eosinophil growth from uncommited stem cells. IL-4 selectively upregulates VCAM-1 expression on endothelial cells thus augmenting VLA-4-dependent eosinophil adhesion. The role of eosinophils in disease is complex but in general their numbers are increased in helminthic parasitic disease and atopic allergy and asthma. Eosinophil products can produce many of the pathological features of asthma, and helminthic larvae coated with immunoglobulin or complement are particularly susceptible to eosinophil-mediated cytotoxicity. Eosinopenia is often related to acute inflammation or stress. PMID:7937446

  5. Does eosinophilic COPD exacerbation have a better patient outcome than non-eosinophilic in the intensive care unit?

    PubMed Central

    Saltürk, Cüneyt; Karakurt, Zuhal; Adiguzel, Nalan; Kargin, Feyza; Sari, Rabia; Celik, M Emin; Takir, Huriye Berk; Tuncay, Eylem; Sogukpinar, Ozlem; Ciftaslan, Nezihe; Mocin, Ozlem; Gungor, Gokay; Oztas, Selahattin

    2015-01-01

    Background COPD exacerbations requiring intensive care unit (ICU) admission have a major impact on morbidity and mortality. Only 10%–25% of COPD exacerbations are eosinophilic. Aim To assess whether eosinophilic COPD exacerbations have better outcomes than non-eosinophilic COPD exacerbations in the ICU. Methods This retrospective observational cohort study was conducted in a thoracic, surgery-level III respiratory ICU of a tertiary teaching hospital for chest diseases from 2013 to 2014. Subjects previously diagnosed with COPD and who were admitted to the ICU with acute respiratory failure were included. Data were collected electronically from the hospital database. Subjects’ characteristics, complete blood count parameters, neutrophil to lymphocyte ratio (NLR), delta NLR (admission minus discharge), C-reactive protein (CRP) on admission to and discharge from ICU, length of ICU stay, and mortality were recorded. COPD subjects were grouped according to eosinophil levels (>2% or ≤2%) (group 1, eosinophilic; group 2, non-eosinophilic). These groups were compared with the recorded data. Results Over the study period, 647 eligible COPD subjects were enrolled (62 [40.3% female] in group 1 and 585 [33.5% female] in group 2). Group 2 had significantly higher C-reactive protein, neutrophils, NLR, delta NLR, and hemoglobin, but a lower lymphocyte, monocyte, and platelet count than group 1, on admission to and discharge from the ICU. Median (interquartile range) length of ICU stay and mortality in the ICU in groups 1 and 2 were 4 days (2–7 days) vs 6 days (3–9 days) (P<0.002), and 12.9% vs 24.9% (P<0.034), respectively. Conclusion COPD exacerbations with acute respiratory failure requiring ICU admission had a better outcome with a peripheral eosinophil level >2%. NLR and peripheral eosinophilia may be helpful indicators for steroid and antibiotic management. PMID:26392758

  6. Eosinophilic Esophagitis in Pediatric and Adolescent Patients

    MedlinePlus

    ... and Adolescent Patients Eosinophilic Esophagitis in Pediatric and Adolescent Patients Basics Overview Eosinophilic esophagitis also known as ( ... children may have vomiting and abdominal pain, and adolescents may complain of the feeling of food getting ...

  7. Allergic Mechanisms in Eosinophilic Esophagitis

    PubMed Central

    Wechsler, Joshua B; Bryce, Paul J

    2014-01-01

    Paralleling the overall trend in allergic diseases, Eosinophilic Esophagitis is rapidly increasing in incidence. It is associated with food antigen-triggered, eosinophil-predominant inflammation and the pathogenic mechanisms have many similarities to other chronic atopic diseases, such as eczema and allergic asthma. Studies in animal models and from patients over the last 15 years have suggested that allergic sensitization leads to food-specific IgE and T-helper lymphocyte type 2 cells, both of which appear to contribute to the pathogenesis along with basophils, mast cells, and antigen-presenting cells. This review will outline our current understandings of the allergic mechanisms that drive eosinophilic esophagitis, drawing from clinical and translational studies in humans as well as experimental animal models. PMID:24813516

  8. Eosinophil-Associated Gene Pathways but not Eosinophil Numbers are Differentially Regulated between Synchrotron Microbeam Radiation Treatment and Synchrotron Broad-Beam Treatment by 48 Hours Postirradiation.

    PubMed

    Ibahim, M J; Yang, Y; Crosbie, J C; Stevenson, A; Cann, L; Paiva, P; Rogers, P A

    2016-01-01

    Synchrotron microbeam radiation treatment (MRT) is a preclinical radiotherapy technique with considerable clinical promise, although some of the underlying radiobiology of MRT is still not well understood. In recently reported studies, it has been suggested that MRT elicits a different tumor immune profile compared to broad-beam treatment (BB). The aim of this study was to investigate the effects of synchrotron MRT and BB on eosinophil-associated gene pathways and eosinophil numbers within and around the tumor in the acute stage, 48 h postirradiation. Balb/C mice were inoculated with EMT6.5 mouse mammary tumors and irradiated with microbeam radiation (112 and 560 Gy) and broad-beam radiation (5 and 9 Gy) at equivalent doses determined from a previous in vitro study. After tumors were collected 24 and 48 h postirradiation, RNA was extracted and quantitative PCR performed to assess eosinophil-associated gene expression. Immunohistochemistry was performed to detect two known markers of eosinophils: eosinophil-associated ribonucleases (EARs) and eosinophil major basic protein (MBP). We identified five genes associated with eosinophil function and recruitment (Ear11, Ccl24, Ccl6, Ccl9 and Ccl11) and all of them, except Ccl11, were differentially regulated in synchrotron microbeam-irradiated tumors compared to broad-beam-irradiated tumors. However, immunohistochemical localization demonstrated no significant differences in the number of EAR- and MBP-positive eosinophils infiltrating the primary tumor after MRT compared to BB. In conclusion, our work demonstrates that the effects of MRT on eosinophil-related gene pathways are different from broad-beam radiation treatment at doses previously demonstrated to be equivalent in an in vitro study. However, a comparison of the microenvironments of tumors, which received MRT and BB, 48 h after exposure showed no difference between them with respect to eosinophil accumulation. These findings contribute to our understanding of the

  9. Eosinophilic esophagitis: diagnosis and management.

    PubMed

    Lieberman, Jay A; Chehade, Mirna

    2012-02-01

    Eosinophilic esophagitis is a clinicopathologic disease that can present with a constellation of upper gastrointestinal symptoms and endoscopic findings in conjunction with significant infiltration of the esophageal tissue with eosinophils. Clinical and histologic resolution of the disease can be seen with dietary restriction therapies and systemic and topical corticosteroids. Because most patients have an atopic background and the disease seems to have an underlying T-helper type 2 pathogenesis, allergists and gastroenterologists need to be familiar with the diagnosis and management of this disease. In this review, clinical characteristics, endoscopic and histologic findings, and available therapy options are discussed. PMID:22244233

  10. Reduced expression of granule proteins during extended survival of eosinophils in splenocyte culture with GM-CSF.

    PubMed

    Ryu, Seul Hye; Na, Hye Young; Sohn, Moah; Han, Sun Murray; Choi, Wanho; In, Hyunju; Hong, Sookyung; Jeon, Hyejin; Seo, Jun-Young; Ahn, Jongcheol; Park, Chae Gyu

    2016-05-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifaceted hematopoietic cytokine and the culture of mouse bone marrow with GM-CSF produces a variety of myeloid cells including granulocytes, macrophages, and dendritic cells. In the present study, we cultured mouse splenocytes with GM-CSF and examined the changes in hematopoietic cell populations over a week. Most of the splenic hematopoietic cells disappeared significantly from culture within 6days with or without the presence of GM-CSF. Among the splenic granulocyte populations, only eosinophils fully survived throughout the culture with GM-CSF for more than a week. During 10days of culture with GM-CSF, splenic eosinophils maintained their morphology as well as most of their surface molecules at high levels, including CCR3 and Siglec F. Meanwhile, the expression of mRNAs encoding major basic protein-1 (MBP-1) and eosinophil peroxidase (EPO), two major eosinophil-derived granule proteins, was diminished significantly from the cultured eosinophils. EPO assays also revealed that eosinophils in culture for more than 5days retained 30% or less EPO activity compared to those in uncultured splenocytes. In contrast, culture of splenocytes with GM-CSF did not change the capacity of eosinophils to migrate in response to eotaxin-1. Our results indicate that mouse splenic eosinophils are effectively cultured for lengthy periods while their expression of eosinophil-derived granule proteins is specifically suppressed. The relevance of these findings to eosinophilic inflammatory response is discussed. PMID:26969350

  11. Development of a suspension array assay in multiplex for simultaneous measurement of serum levels of four eosinophil granule proteins

    PubMed Central

    Makiya, Michelle A.; Herrick, Jesica A.; Khoury, Paneez; Prussin, Calman P.; Nutman, Thomas B.; Klion, Amy D.

    2014-01-01

    The concentrations of major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EPO) have been associated with eosinophilic disease severity. Whereas a variety of techniques have been used to measure individual eosinophil granule protein concentration, none of these methods efficiently measures MBP, ECP, EDN and EPO simultaneously. A multiplex suspension array system was developed to simultaneously measure the concentration of MBP, ECP, EDN and EPO in serum. The assay showed excellent inter- and intra-assay reliability, and serum levels of MBP, ECP and EDN from eosinophilic subjects analyzed by ELISA and multiplex were highly correlated (r = 0.8579; P < 0.0001, r = 0.6356; P = 0.0006 and r = 0.8600; P < 0.0001, respectively, Spearman rank correlation). Moreover, the multiplex assay required 500-fold less serum than a single ELISA to achieve comparable sensitivity. Absolute eosinophil count and eosinophil surface expression of the activation marker, CD69, were significantly correlated with concentrations of MBP, EDN and EPO, but not ECP, in serum from eosinophilic subjects. Furthermore, subjects with eosinophilic gastrointestinal disorder and normal peripheral absolute eosinophil counts (< 0.5 × 109/L) had significantly increased concentrations of MBP (P < 0.0001), ECP (P < 0.0001), EDN (P = 0.0001) and EPO (P < 0.0001) compared to normal donors. In summary, the eosinophil granule protein multiplex assay provides a rapid and reliable way to measure eosinophil granule protein levels and should prove useful in assessing patterns of degranulation in patients with eosinophilic disorders. PMID:24914990

  12. Eosinophilic ascites, as a rare presentation of eosinophilic gastroenteritis

    PubMed Central

    Cuko, L; Bilaj, F; Bega, B; Barbullushi, A; Resuli, B

    2014-01-01

    Background: Eosinophilic ascites is the most unusual presentation of eosinophilic gastroenteritis (EGE), caused by edema and eosinophilic inflammation of the small bowel wall's serosal layer. Case Report: We report the case of a 37-year-old woman, who presented with diffuse abdominal pain, nausea, abdominal distension, moderate ascites and diarrhea of two weeks duration. The rest of physical and clinical examination was unremarkable, and her past medical history was uneventful. Magnetic Resonance Imaging showed the presence of ascites and diffuse thickening of small bowel wall, but did not detect a primary malignancy in the abdominal cavity; and no signs of portal hypertension or liver damage. Laboratory test results revealed essential peripheral blood eosinophilia, elevated serum IgE and marked increase of eosinophils in the abdominal fluid. Treatment with corticosteroids normalized laboratory tests results, and the ascites resolved immediately. Conclusions: EGE is a rare entity and it should be kept in mind in patients of unexplained ascites. The absence of primary malignancy on imaging, coupled with marked increase of fluid esinophilia and immediate response to treatment with steroids, confirm indirectly the diagnosis of EGE. Hippokratia 2014; 18 (3): 275-277. PMID:25694765

  13. Eosinophilic annular erythema in childhood - Case report.

    PubMed

    Abarzúa, Alvaro; Giesen, Laura; Silva, Sergio; González, Sergio

    2016-01-01

    Eosinophilic annular erythema is a rare, benign, recurrent disease, clinically characterized by persistent, annular, erythematous lesions, revealing histopathologically perivascular infiltrates with abundant eosinophils. This report describes an unusual case of eosinophilic annular erythema in a 3-year-old female, requiring sustained doses of hydroxychloroquine to be adequately controlled. PMID:27579748

  14. Eosinophilic annular erythema in childhood - Case report*

    PubMed Central

    Abarzúa, Alvaro; Giesen, Laura; Silva, Sergio; González, Sergio

    2016-01-01

    Eosinophilic annular erythema is a rare, benign, recurrent disease, clinically characterized by persistent, annular, erythematous lesions, revealing histopathologically perivascular infiltrates with abundant eosinophils. This report describes an unusual case of eosinophilic annular erythema in a 3-year-old female, requiring sustained doses of hydroxychloroquine to be adequately controlled. PMID:27579748

  15. Role of advanced diagnostics for eosinophilic esophagitis.

    PubMed

    Hirano, Ikuo

    2014-01-01

    In eosinophilic esophagitis (EoE), diagnostic tests aid in the identification of pathophysiologic consequences and accurate detection of the disease. The EoE Endoscopic Reference Score (EREFS) classifies and grades the severity of the five major endoscopically identified esophageal features of EoE (edema, rings, exudates, furrows and strictures). The EREFS may be useful in the evaluation of disease severity and as an objective outcome of response to therapy. pH monitoring identifies the presence of abnormal degrees of acid exposure in the esophagus that characterizes gastroesophageal reflux disease. The presence of acid reflux, however, does not indicate that the reflux is responsible for esophageal eosinophilia. Esophageal manometry has not demonstrated a characteristic abnormality with sufficient sensitivity to make the test of diagnostic value in clinical practice. On the other hand, manometric characteristics of esophageal pressurization and longitudinal muscle dysfunction may help identify important pathophysiologic consequences of EoE. Esophageal impedance testing has demonstrated increased baseline mucosal impedance that correlates with increased epithelial permeability in EoE. Reduced mucosal integrity may provide intraluminal allergens access to antigen-presenting cells, serving as an early event in the pathogenesis of EoE. The functional luminal impedance probe (FLIP) provides quantitative assessment of esophageal mural compliance, a physiologic correlate of remodeling in EoE. Studies using FLIP have associated reductions in esophageal distensibility in EoE with the important outcome of food impaction risk. Finally, confocal endomicroscopy, multiphoton fluorescence microscopy and novel eosinophil-enhancing contrast agents are emerging methods that may allow for in vivo visualization of esophageal eosinophilic inflammation, thereby improving the detection and understanding of this emerging disease. PMID:24603385

  16. Eosinophils in mucosal immune responses

    PubMed Central

    Travers, J; Rothenberg, M E

    2015-01-01

    Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

  17. Strongyloidiasis histologically mimicking eosinophilic folliculitis.

    PubMed

    Cannavò, Serafinella P; Guarneri, Fabrizio; Guarneri, Claudio

    2004-01-01

    The authors report an unusual case of strongyloidiasis in an Italian patient, who has always lived in Sicily. The patient presented with marked blood eosinophilia and an itching maculo-papular eruption, histologically simulating eosinophilic folliculitis. The clinical resolution was achieved after albendazol therapy. PMID:15319162

  18. Human eosinophil innate response to Alternaria fungus through protease-activated receptor-2.

    PubMed

    Matsuwaki, Yoshinori; Wada, Kota; Moriyama, Hiroshi; Kita, Hirohito

    2011-01-01

    Eosinophils are multifunctional leukocytes implicated in the pathogenesis of allergic diseases. An association between eosinophilic inflammation and infection or colonization by fungi has also been long recognized. However, the mechanisms underlying how eosinophils are activated and how they release proinflammatory and immunomodulatory mediators such as major basic protein (MBP) and eosinophil-derived neurotoxin remain largely unknown. We used a fungus, i.e. Alternaria, as a model microbe relevant to human asthma and chronic rhinosinusitis (CRS) to investigate the molecular mechanisms involved in the immune recognition of ubiquitous environmental allergens. Human eosinophils are activated by live Alternaria alternata organisms, release their granule proteins, and kill the fungi. Eosinophils, but not neutrophils, respond to secreted products from A. alternata. We found that eosinophils are equipped with innate cellular activation machinery that responds to an extracellular aspartate protease secreted by Alternaria. Aspartate protease activation of protease-activated receptor (PAR)-2 probably involves a novel mechanism different from that for serine protease activation of PAR-2. Thus, human eosinophils may recognize certain danger signals or virulence factors produced by fungi and provoke inflammatory responses against these organisms. Dysregulation of such an innate immune mechanism may be involved in the pathophysiology of certain human inflammatory diseases, including asthma and CRS. PMID:21646807

  19. Diethylcarbamazine and Non-Diethylcarbamazine Related Bancroftian Granuloma: An Immunohistochemical Study of Eosinophil Toxic Proteins

    PubMed Central

    Figueredo-Silva, Jose; Cavalcanti, Carmelita; Montenegro, Luciano Tavares; Norões, Joaquim; Dreyer, Gerusa

    2010-01-01

    It has been suggested, mostly using in vitro experiments, that defenses against parasites involve mainly activated eosinophils and their toxic proteins, such as major basic protein (MBP), eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO). Eosinophil degranulation has been described around degenerating onchocercal microfilariae in patients treated with diethylcarbamazine (DEC). In bancroftian filariasis, traditional histopathologic studies have shown remarkable numbers of eosinophils in granulomatous lesions associated with both DEC-induced and spontaneous death of adult Wuchereria bancrofti parasites. No immunohistochemical study targeting eosinophil degranulation has been previously performed in these granulomas, which are found mainly within intrascrotal lymphatic vessels. This investigation was undertaken in 22 (12 DEC-treated and 10 untreated) male patients in order to determine the immunohistochemical expressions of MBP, EPO and ECP in bancofitian granulomas, using the indirect method. Stained intact esosinophils, as well as granular, extra-cellular material positive for all three proteins, were found in all granulomas. The immunohistochemical patterns were similar in both DEC-treated and untreated cases, irrespective of microfilaremia, blood eosinophilia, and granuloma age. Positive intact cells were observed mostly at the periphery of the granulomas, whereas granular material predominated in central areas around dead or degenerating parasites. These results indicate that eosinophils accumulate in the granulomas and degranulate preferentially in close proximity to degenerating or dead adult parasites. In bancroftian granulomas, influx and degranulation of eosinophils are considered a consequence of parasite death, rather than its cause. PMID:23675184

  20. Human peripheral blood eosinophils induce angiogenesis.

    PubMed

    Puxeddu, Ilaria; Alian, Akram; Piliponsky, Adrian Martin; Ribatti, Domenico; Panet, Amos; Levi-Schaffer, Francesca

    2005-03-01

    Eosinophils play a crucial role in allergic reactions and asthma. They are also involved in responses against parasites, in autoimmune and neoplastic diseases, and in fibroses. There is increasing evidence that angiogenesis plays an important role in these processes. Since eosinophils are known to produce angiogenic mediators, we have hypothesized a direct contribution of these cells to angiogenesis. The effect of human peripheral blood eosinophil sonicates on rat aortic endothelial cell proliferation (in vitro), rat aorta sprouting (ex vivo) and angiogenesis in the chick embryo chorioallantoic membrane (in vivo) have been investigated. To determine whether eosinophil-derived vascular endothelial growth factor influences the eosinophil pro-angiogenic activity, eosinophil sonicates were incubated with anti-vascular endothelial growth factor antibodies and then added to the chorioallantoic membrane. Vascular endothelial growth factor mRNA expression and vascular endothelial growth factor receptor density on the endothelial cells were also evaluated. Eosinophils were found to enhance endothelial cell proliferation and to induce a strong angiogenic response both in the aorta rings and in the chorioallantoic membrane assays. Pre-incubation of eosinophil sonicates with anti-vascular endothelial growth factor antibodies partially reduced the angiogenic response of these cells in the chorioallantoic membrane. Eosinophils also increased vascular endothelial growth factor mRNA production on endothelial cells. Eosinophils are able to induce angiogenesis and this effect is partially mediated by their pre-formed vascular endothelial growth factor. This strongly suggests an important role of eosinophils in angiogenesis-associated diseases such as asthma. PMID:15618019

  1. Eosinophilic Gastritis Presenting as Tissue Necrosis

    PubMed Central

    Jo, Yong Min; Jang, Jin Seok; Han, Seung Hee; Kang, Sang Hyun; Kim, Woo Jae; Jeong, Jin Sook

    2015-01-01

    Eosinophilic gastroenteritis is very rare disorder that is characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of any definite causes of eosinophilia. It is associated with various clinical gastrointestinal manifestations, and depends on the involved layer and site. We report a case of eosinophilic gastritis presenting with severe necrosis. The symptoms disappeared immediately after beginning steroid treatment, and the eosinophil count decreased to the reference range. The patient showed eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis. It is a unique presentation of eosinophilic gastritis. To the best of our knowledge, no case of eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis has been previously reported in Korea. PMID:26668805

  2. Treatment of eosinophilic esophagitis by dilation.

    PubMed

    Schoepfer, Alain

    2014-01-01

    Treatment options for eosinophilic esophagitis (EoE) include drugs, diets and esophageal dilation. Esophageal dilation can be performed using either through-the-scope balloons or wire-guided bougies. Dilation can lead to long-lasting symptom improvement in EoE patients presenting with esophageal strictures. Esophageal strictures are most often diagnosed when the 8- to 9-mm outer diameter adult gastroscope cannot be passed any further or only against resistance. A defined esophageal diameter to be targeted by dilation is missing, but the majority of patients have considerable symptomatic improvement when a diameter of 16-18 mm has been reached. A high complication rate, especially regarding esophageal perforations, has been reported in small case series until 2006. Several large series were published in 2007 and later that demonstrated that the complication risk (especially esophageal perforation) was much lower than what was reported in earlier series. The procedure can therefore be regarded as safe when some simple precautions are followed. It is noteworthy that esophageal dilation does not influence the underlying eosinophil-predominant inflammation. Patients should be informed before the procedure that postprocedural retrosternal pain may occur for some days, but that it usually responds well to over-the-counter analgesics such as paracetamol. Dilation-related superficial lacerations of the mucosa should not be regarded and reported as complications, but instead represent a desired effect of the therapy. Patient tolerance and acceptance for esophageal dilation have been reported to be good. PMID:24603396

  3. The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking.

    PubMed

    Schratl, Petra; Royer, Julia F; Kostenis, Evi; Ulven, Trond; Sturm, Eva M; Waldhoer, Maria; Hoefler, Gerald; Schuligoi, Rufina; Lippe, Irmgard Th; Peskar, Bernhard A; Heinemann, Akos

    2007-10-01

    Prostaglandin (PG) D2 is a major mast cell product that acts via two receptors, the D-type prostanoid (DP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptors. Whereas CRTH2 mediates the chemotaxis of eosinophils, basophils, and Th2 lymphocytes, the role of DP has remained unclear. We report in this study that, in addition to CRTH2, the DP receptor plays an important role in eosinophil trafficking. First, we investigated the release of eosinophils from bone marrow using the in situ perfused guinea pig hind limb preparation. PGD2 induced the rapid release of eosinophils from bone marrow and this effect was inhibited by either the DP receptor antagonist BWA868c or the CRTH2 receptor antagonist ramatroban. In contrast, BWA868c did not inhibit the release of bone marrow eosinophils when this was induced by the CRTH2-selective agonist 13,14-dihydro-15-keto-PGD2. In additional experiments, we isolated bone marrow eosinophils from the femoral cavity and found that these cells migrated toward PGD2. We also observed that BWA868c inhibited this response to a similar extent as ramatroban. Finally, using immunohistochemistry we could demonstrate that eosinophils in human bone marrow specimens expressed DP and CRTH2 receptors at similar levels. Eosinophils isolated from human peripheral blood likewise expressed DP receptor protein but at lower levels than CRTH2. In agreement with this, the chemotaxis of human peripheral blood eosinophils was inhibited both by BWA868c and ramatroban. These findings suggest that DP receptors comediate with CRTH2 the mobilization of eosinophils from bone marrow and their chemotaxis, which might provide the rationale for DP antagonists in the treatment of allergic disease. PMID:17878378

  4. Anti-Siglec-F Antibody Reduces Allergen-Induced Eosinophilic Inflammation and Airway Remodeling1

    PubMed Central

    Song, Dae Jin; Cho, Jae Youn; Lee, Sang Yeub; Miller, Marina; Rosenthal, Peter; Soroosh, Pejman; Croft, Michael; Zhang, Mai; Varki, Ajit; Broide, David H.

    2009-01-01

    Siglec-F is a sialic acid-binding Ig superfamily receptor that is highly expressed on eosinophils. We have investigated whether administration of an anti-Siglec-F Ab to OVA-challenged wild-type mice would reduce levels of eosinophilic inflammation and levels of airway remodeling. Mice sensitized to OVA and challenged repetitively with OVA for 1 mo who were administered an anti-Siglec-F Ab had significantly reduced levels of peribronchial eosinophilic inflammation and significantly reduced levels of subepithelial fibrosis as assessed by either trichrome staining or lung collagen levels. The anti-Siglec-F Ab reduced the number of bone marrow, blood, and tissue eosinophils, suggesting that the anti-Siglec-F Ab was reducing the production of eosinophils. Administration of a F(ab′)2 fragment of an anti-Siglec-F Ab also significantly reduced levels of eosinophilic inflammation in the lung and blood. FACS analysis demonstrated increased numbers of apoptotic cells (annexin V+/CCR3+ bronchoalveolar lavage and bone marrow cells) in anti-Siglec-F Ab-treated mice challenged with OVA. The anti-Siglec-F Ab significantly reduced the number of peribronchial major basic protein+/TGF-β+ cells, suggesting that reduced levels of eosinophil-derived TGF-β in anti-Siglec-F Ab-treated mice contributed to reduced levels of peribronchial fibrosis. Administration of the anti-Siglec-F Ab modestly reduced levels of periodic acid-Schiff-positive mucus cells and the thickness of the smooth muscle layer. Overall, these studies suggest that administration of an anti-Siglec-F Ab can significantly reduce levels of allergen-induced eosinophilic airway inflammation and features of airway remodeling, in particular subepithelial fibrosis, by reducing the production of eosinophils and increasing the number of apoptotic eosinophils in lung and bone marrow. PMID:19783675

  5. Current Approach to Diagnosis and Management of Pulmonary Eosinophilic Syndromes: Eosinophilic Pneumonias, Eosinophilic Granulomatosis with Polyangiitis, and Hypereosinophilic Syndrome.

    PubMed

    Sergew, Amen; Fernández Pérez, Evans R

    2016-06-01

    Eosinophils play a key role in orchestrating the complex clinicopathological pulmonary and extrapulmonary disease features in patients with eosinophilic syndromes. Eosinophilic pulmonary syndromes consist of a heterogeneous group of disorders characterized by the presence of peripheral blood eosinophilia and/or eosinophilic-related pulmonary impairment. These disorders can present with varying degrees of organ involvement, and while their presentation may be similar, it is important to define the disease state, as management and prognosis differ. In this article, we discuss acute and chronic eosinophilic pneumonias, eosinophilic granulomatosis with polyangiitis, and the hypereosinophilic syndromes. The mainstay of therapy for these disorders has been corticosteroids; however, recent and ongoing studies have provided strong grounds for optimism for specific targeted treatment approaches. PMID:27231866

  6. Eosinophilic phenotypes of airway disease.

    PubMed

    Pavord, Ian D

    2013-12-01

    Our understanding of the clinical implications of eosinophilic airway inflammation has increased significantly over the last 20 years, aided by the development of noninvasive means to assess it. This pattern of airway inflammation can occur in a diverse range of airway diseases. It is associated with a positive response to corticosteroids and a high risk of preventable exacerbations. Our new understanding of the role of eosinophilic airway inflammation has paved the way for the clinical development of a number of more specific inhibitors that may become new treatment options. Different definitions, ideas of disease, and adoption of biomarkers that are not well known are necessary to fully realize the potential of these treatments. PMID:24313765

  7. Eosinophilic leukaemia in a cat.

    PubMed

    Sharifi, Hassan; Nassiri, Seyed Mahdi; Esmaelli, Hossein; Khoshnegah, Javad

    2007-12-01

    A 14-year-old female domestic shorthair cat was presented to Tehran University Veterinary Teaching Hospital for a persistent fever, anorexia, intermittent vomiting, weight loss and weakness. The main clinical signs were pale mucous membranes, dehydration and splenomegaly. The complete blood count and serum biochemistry tests revealed non-regenerative anaemia, thrombocytopenia and increased alkaline phosphatase (ALP) activity. An enzyme-linked immunosorbent assay (ELISA) test for feline leukaemia virus was negative. Blood film and bone marrow examination revealed a large number of immature eosinophils with variable sizes and numbers of faintly azurophilic granules. Cytochemical staining of blood film demonstrated 70% positive cells for ALP activity. Four percent CD34 positive cells were detected by flow cytometry. As eosinophilic leukaemia is difficult to identify by light microscopy, well-defined diagnostic criteria and the use of flow cytometry and cytochemical staining can improve the ability to correctly diagnose this type of leukaemia in cats. PMID:17669677

  8. Eosinophilic fasciitis after parasite infection

    PubMed Central

    Patinha, Fabia; Marinho, Antonio

    2016-01-01

    Eosinophilic fasciitis is a systemic inflammatory disease characterized by symmetrical swelling and skin induration of the distal portions of the arms and/or legs, evolving into a scleroderma-like appearance, accompanied by peripheral blood eosinophilia. It is a rare disease with a poorly understood etiology. Corticosteroid treatment remains the standard therapy, either taken alone or in association with an immunosuppressive drug. This paper presents a case of a male patient with palpebral edema and marked eosinophilia, diagnosed with intestinal parasitic infection in October 2006. He was treated with an antiparasitic drug, but both the swelling and the analytical changes remained. This was followed by a skin and muscle biopsy, which turned out to be compatible with eosinophilic fasciitis. There was progressive worsening of the clinical state, with stiffness of the abdominal wall and elevated inflammatory parameters, and the patient was referred to the Immunology Department, medicated with corticosteroids and methotrexate. Over the years there were therapeutic adjustments and other causes were excluded. Currently the patient continues to be monitored, and there is no evidence of active disease. The case described in this article is interesting because of the diagnosis of eosinophilic fasciitis probably associated/coexisting with a parasite infection. This case report differs from others in that there is an uncommon cause associated with the onset of the disease, instead of the common causes such as trauma, medication, non-parasitic infections or cancer. PMID:27407276

  9. [Eosinophilic oesophagitis in bronchial asthma].

    PubMed

    Mikhaleva, L M; Barkhina, T G; Golovanova, V E; Shchegoleva, N N; Gracheva, N A

    2012-01-01

    Combination of bronchial asthma and gastrointestinal pathology is frequently encountered in clinical practice. Clinical symptoms of this condition are highly diversified and gastrointestinal diseases play an important role in exacerbation of bronchial asthma. The prevalence of allergic diseases has recently become rampant. Eosinophilic oesophagitis is worth of special attention because its histological criteria, unlike clinical ones, are well defined. They include chronic immune antigen-mediated inflammatory oesophageal disease with pronounced intraepithelial eosinophilic infiltration and clinical symptoms resulting from oesophageal dysfunction that resemble manifestations of gastroesophageal reflux disease but fail to respond to antireflux and antacid therapy. Many specific and practical aspects of the problem remain to be elucidated. The poor awareness of clinicians of this disease hampers its adequate diagnostics and treatment. In order to revise and optimize the former diagnostic and therapeutic algorithm., an interdisciplinary expert group was set up in 2010 constituted by specialists of the American College of Gastroenterology, American Academy of Asthma, Allergy and Immunology, and Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Results of the work of this group together with the literature data on eosinophilic esopahgitis are discussed in the present review. PMID:23516863

  10. Eosinophilic fasciitis after parasite infection.

    PubMed

    Oliveira, Marta; Patinha, Fabia; Marinho, Antonio

    2016-01-01

    Eosinophilic fasciitis is a systemic inflammatory disease characterized by symmetrical swelling and skin induration of the distal portions of the arms and/or legs, evolving into a scleroderma-like appearance, accompanied by peripheral blood eosinophilia. It is a rare disease with a poorly understood etiology. Corticosteroid treatment remains the standard therapy, either taken alone or in association with an immunosuppressive drug. This paper presents a case of a male patient with palpebral edema and marked eosinophilia, diagnosed with intestinal parasitic infection in October 2006. He was treated with an antiparasitic drug, but both the swelling and the analytical changes remained. This was followed by a skin and muscle biopsy, which turned out to be compatible with eosinophilic fasciitis. There was progressive worsening of the clinical state, with stiffness of the abdominal wall and elevated inflammatory parameters, and the patient was referred to the Immunology Department, medicated with corticosteroids and methotrexate. Over the years there were therapeutic adjustments and other causes were excluded. Currently the patient continues to be monitored, and there is no evidence of active disease. The case described in this article is interesting because of the diagnosis of eosinophilic fasciitis probably associated/coexisting with a parasite infection. This case report differs from others in that there is an uncommon cause associated with the onset of the disease, instead of the common causes such as trauma, medication, non-parasitic infections or cancer. PMID:27407276

  11. Eosinophilic jejunitis presenting as intractable abdominal pain.

    PubMed

    Mungan, Zeynel; Attila, Tan; Kapran, Yersu; Tokatli, Ilyas Pinar; Unal, Zeynep

    2014-09-01

    Eosinophilic gastroenteritis is an uncommon disease characterized by eosinophilic infiltration of the gastrointestinal tract. The clinical manifestations are related to the layer(s) and extent of the bowel involved. In this paper, we present a case of intractable abdominal pain caused by jejunal submucosal eosinophilic infiltration without mucosal involvement, diagnosed by deep endoscopic biopsies. The patient was successfully treated with steroids without need for surgery for diagnosis or therapy. PMID:25565932

  12. [Eosinophilic esophagitis: a rare cause of dysphagia].

    PubMed

    Billot, D; Pernin, M; Pillot, C; Bredin, C; Hoeffler, P; Graffin, B; Rey, P

    2010-12-01

    Eosinophilic esophagitis is an unrecognized and emerging entity. Its incidence increases with allergic disorders. A 29-year-old man presented with a 4-year history of intermittent and paroxysmal dysphagia. The triad including allergy, young age, and impaction of foreign bodies, combined with a chronic dysphagia is almost pathognomonic of eosinophilic esophagitis. Endoscopic esophageal features can be diverse, so systematic esophageal biopsies are required. Diagnosis is established with the demonstration of an eosinophilic infiltrate with a cell count exceeding 15 eosinophils per high power field (×400). First line therapy includes swallowed topical corticosteroids and removal of an allergic cause, when it could be identified. PMID:20605659

  13. Eosinophils: changing perspectives in health and disease

    PubMed Central

    Rosenberg, Helene F.; Dyer, Kimberly D.; Foster, Paul S.

    2015-01-01

    Eosinophils have been traditionally perceived as largely end-stage, cytotoxic effector cells. Recent studies have profoundly altered this simplistic view of eosinophils and their function. New insights into the molecular basis of development, trafficking and degranulation of eosinophils have provided a better understanding of the role of these cells in promoting homeostasis through their immunomodulatory functions. Likewise, recent developments have generated a more sophisticated view of how eosinophils contribute to the pathogenesis of disease, including asthma and primary hypereosinophilic syndromes, and also a more complete appreciation of their activities in parasitic infection. PMID:23154224

  14. Eosinophilic Disorders of the Gastrointestinal Tract.

    PubMed

    Samiullah; Bhurgri, Hadi; Sohail, Umair

    2016-09-01

    Eosinophilic gastrointestinal disorders represent a spectrum of disorders demonstrating gastrointestinal eosinophilia without any known cause for eosinophilia. Pathogenesis is not clearly established, but immune responses to dietary antigens are implicated. These disorders affect children and adults and are seen in association with allergic disorders. Eosinophilic esophagitis is diagnosed in the setting of mucosal eosinophilia on endoscopic biopsy and symptoms of esophageal dysfunction. Eosinophilic gastroenteritis is also diagnosed with endoscopic biopsies. Eosinophilic colitis commonly presents with lower gastrointestinal symptoms and is a diagnosis of exclusion. PMID:27545738

  15. The Consequences of Not Having Eosinophils

    PubMed Central

    Gleich, G. J.; Klion, A. D.; Lee, J. J.; Weller, P. F.

    2014-01-01

    Several lines of evidence suggest that deficiency of eosinophils is not associated with any characteristic abnormality. Patients lacking eosinophils, in the setting of immunodeficiency or as a consequence of IgG-mediated eosinophil precursor destruction, do not display any distinguishing abnormalities related to eosinophil reduction. The observation that eosinophil-deficient mice do not display any distinctive syndrome or failure of their health is evidence that, under ordinary laboratory conditions, the eosinophil does not play a critical role in the well-being of mammals. Observations that monoclonal antibodies to interleukin-5 (IL-5) are well tolerated appear unsurprising in light of these findings. For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. Safety data for reslizumab, another anti-IL-5 monoclonal antibody, and benralizumab, a monoclonal antibody to the IL-5 receptor α-chain, are comparatively limited, especially for benralizumab, although reports of administration of these antibodies to humans suggest that they are well tolerated. Thus, data to the present suggest that reduction of eosinophils appears to have no characteristic ill effects on normal health, and monoclonal antibodies that deplete eosinophils have the potential to be widely employed in the treatment of eosinophil-associated diseases. PMID:23742015

  16. Associations between peripheral blood eosinophil counts in patients with systemic sclerosis and disease severity.

    PubMed

    Ando, Katsutoshi; Nakashita, Tamao; Kaneko, Norihiro; Takahashi, Kazuhisa; Motojima, Shinji

    2016-01-01

    Increased levels of serum pro-fibrotic cytokines have been reported in patients with systemic sclerosis (SSc). Some of these cytokines also play an important role in the differentiation and migration of eosinophils. The aim of this study was to determine whether eosinophilic inflammation is caused in SSc. We retrospectively reviewed the peripheral blood eosinophil counts in 70 untreated patients with SSc and compared them with those in patients with other major collagen diseases. We additionally evaluated a possible association with disease severity. Eosinophil counts were significantly higher levels in patients with SSc than in those with other collagen diseases, whereas total leukocyte counts were not. Eosinophil counts correlated positively with both severe interstitial lung disease (ILD; r = 0.255, p = 0.033) and modified Rodnan total skin thickness score (m-Rodnan TSS) in SSc (r = 0.347, p = 0.003), but did not correlate with ILD severity in other collagen diseases. In conclusion, peripheral eosinophil counts were higher in patients with SSc than in those with other collagen diseases and were correlated with increased disease severity. Our data suggest that eosinophilic inflammation is involved in the pathogenesis and progression of SSc. PMID:27610320

  17. Genetics Home Reference: PDGFRB-associated chronic eosinophilic leukemia

    MedlinePlus

    ... associated chronic eosinophilic leukemia PDGFRB-associated chronic eosinophilic leukemia Enable Javascript to view the expand/collapse boxes. ... All Close All Description PDGFRB -associated chronic eosinophilic leukemia is a type of cancer of blood-forming ...

  18. Eosinophilic Esophagitis: A Comprehensive Review.

    PubMed

    Cianferoni, Antonella; Spergel, Jonathan

    2016-04-01

    Eosinophilic esophagitis (EoE) is an emerging chronic atopic clinical-pathologic disease with an estimated prevalence of 1/1000 similar to the one of Crohn's diseases. Usually, EoE is firstly suspected due to symptoms that are caused by esophageal dysfunction and/or fibrosis. EoE diagnosis is confirmed if the esophageal biopsy shows at least 15 eosinophils per high power field (eos/hpf) as a peak value in one or more of at least four specimens obtained randomly from the esophagus. Most of the patients affected by EoE have other atopic diseases such as allergic rhinitis, asthma, IgE-mediated food allergies, and/or atopic dermatitis. The local inflammation is a T helper type 2 (Th2) flogosis, which most likely is driven by a mixed IgE and non-IgE-mediated reaction to food and/or environmental allergens. Recently published genetic studies showed also that EoE is associated with single nucleotide polymorphism (SNP) on genes which are important in atopic inflammation such as thymic stromal lymphopoietin (TSLP) located close to the Th2 cytokine cluster (IL-4, IL-5, IL-13) on chromosome 5q22. When the EoE diagnosis is made, it is imperative to control the local eosinophilic inflammation not only to give symptomatic relief to the patient but also to prevent complications such as esophageal stricture and food impaction. EoE is treated like many other atopic diseases with a combination of topical steroids and/or food antigen avoidance. PMID:26194940

  19. Eosinophils in hereditary and inflammatory myopathies.

    PubMed

    Schröder, Thomas; Fuchss, Johann; Schneider, Ilka; Stoltenburg-Didinger, Gisela; Hanisch, Frank

    2013-12-01

    It is not known whether eosinophilic myositis is a specific histopathological feature of limb girdle muscular dystrophy 2A (LGMD2A). Number and location of eosinophils in skeletal muscle biopsies (n=100) was analysed by Giemsa and modified hematoxylin/eosin staining in patients with genetically confirmed myopathies (LGMD2A, LGMD2B, LGMD2L, facioscapulohumeral muscular dystrophy, dystrophinopathy), histologically confirmed idiopathic inflammatory myopathies (sporadic inclusion body myositis (sIBM), dermatomyositis (DM), polymyositis), amyotrophic lateral sclerosis (neurogenic control), and normal controls. The number of eosinophils/mm² was significantly higher in LGMD2A, PM, DM, and sIBM compared to controls but not significantly higher than other myopathies. A large overlap in the number of eosinophils/mm2 between all groups was seen. In all disease groups eosinophils were mainly found endomysially (46- 88%) and intra- and perivascularly (4-37%). There was no correlation between the numbers of eosinophils/mm² and (i) age at biopsy and (ii) the duration of the disease. The extent of myopathic, fibrotic, and inflammatory changes did not differ in samples with high and low eosinophil count. Eosinophils seem to represent an unspecific histological finding in hereditary and inflammatory myopathies, but also amyotrophic lateral sclerosis. PMID:24803842

  20. Full recovery from Baylisascaris procyonis eosinophilic meningitis.

    PubMed

    Pai, Poulomi J; Blackburn, Brian G; Kazacos, Kevin R; Warrier, Rajasekharan P; Bégué, Rodolfo E

    2007-06-01

    Infection by Baylisascaris procyonis is an uncommon but devastating cause of eosinophilic meningitis. We report the first case-patient, to our knowledge, who recovered from B. procyonis eosinophilic meningitis without any recognizable neurologic deficits. The spectrum of illness for this organism may be wider than previously recognized. PMID:17553240

  1. Gallium-67 pulmonary uptake in eosinophilic pneumonia

    SciTech Connect

    Morais, J.; Carrier, L.; Gariepy, G.; Le Bel, L.; Chartrand, R.; Picard, D.

    1988-01-01

    Eosinophilic pneumonia is usually diagnosed based on the findings on chest x-ray, white blood count, and transbronchial biopsy. After reporting a case of Ga-67 lung uptake in eosinophilic pneumonia, its histopathology is discussed and the mechanisms of Ga-67 uptake by inflammatory lesions are reviewed.

  2. Antagonism of eosinophil accumulation in asthma.

    PubMed

    Walsh, Garry M

    2010-11-01

    There is considerable evidence that implicates eosinophils as important effector cells and immunomodulators in the inflammation characteristic of asthma. Numerous in vitro and animal studies have demonstrated essential roles for cell adhesion molecules in eosinophil adhesion and transendothelial migration including the selectins, ICAM-1, VCAM-1 together with many of the 1 and β2 integrins. A large body of evidence has also implicated several cytokines and chemokines in the selective recruitment of eosinophils to sites of asthmatic inflammation. Biopharmaceutical approaches have been used to identify inhibitory molecules that target key elements in the processes controlling eosinophil accumulation in asthma. This review will summarise, the problems and successes regarding recent patents and developments in adhesion-based therapeutic strategies aimed at reducing eosinophil-mediated inflammation in the asthmatic lung. PMID:20804449

  3. β-lactam-associated eosinophilic colitis.

    PubMed

    Mogilevski, Tamara; Nickless, David; Hume, Sam

    2015-01-01

    A 42-year-old man with a history of childhood asthma presented with a 2-week history of watery diarrhoea and marked peripheral eosinophilia in the setting of recent use of cephalexin. His colonoscopy revealed patchy colitis. Biopsies were consistent with eosinophilic colitis. Two months later he received a course of amoxicillin resulting in recurrence of peripheral eosinophilia. Given the time-frame of β-lactam administration to symptom onset and elimination of all other precipitating causes, he was diagnosed with β-lactam-associated eosinophilic colitis. The patient's symptoms resolved and peripheral eosinophil count decreased with no specific treatment. Eosinophilic colitis is a rare heterogeneous condition, the pathogenesis of which is likely to be an interplay between environmental and genetic factors. It can be secondary to a helminthic infection or a drug reaction and has been associated with ulcerative colitis. If secondary causes of eosinophilic colitis have been excluded, the mainstay of treatment is with corticosteroids. PMID:26106168

  4. Clinical evaluation of eosinophils in the sputum.

    PubMed Central

    Vieira, V G; Prolla, J C

    1979-01-01

    The sputum differential eosinophil/neutrophil count was done in 384 patients using Leishman staining. The patients were distributed in four groups: bronchial asthma (197 patients); chronic bronchitis with wheezing (45 patients); chronic bronchitis and/or emphysema without wheezing (73 patients); other pulmonary diseases (64 patients). Eosinophils were present in patients from all groups but more frequently (P less than 0.001) in asthma: 142 (72%) of 197 patients. In bronchial asthma and chronic bronchitis with wheezing the percentages of eosinophils were more frequently (P less than 0.001) above 80%: 57% and 58% of the patients respectively. The other two groups had more cases with 19% or less eosinophils. There is no percentage level specific for asthma but levels above 80% of eosinophils are strongly suggestive of asthma or of chronic bronchitis with wheezing. PMID:521497

  5. The pathophysiology of eosinophilic esophagitis.

    PubMed

    Raheem, Mayumi; Leach, Steven T; Day, Andrew S; Lemberg, Daniel A

    2014-01-01

    Eosinophilic esophagitis (EoE) is an emerging disease characterized by esophageal eosinophilia (>15eos/hpf), lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast-cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with transforming growth factor-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE. PMID:24910846

  6. The Pathophysiology of Eosinophilic Esophagitis

    PubMed Central

    Raheem, Mayumi; Leach, Steven T.; Day, Andrew S.; Lemberg, Daniel A.

    2014-01-01

    Eosinophilic esophagitis (EoE) is an emerging disease characterized by esophageal eosinophilia (>15eos/hpf), lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast-cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with transforming growth factor-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE. PMID:24910846

  7. Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation.

    PubMed

    Ueki, Shigeharu; Tokunaga, Takahiro; Fujieda, Shigeharu; Honda, Kohei; Hirokawa, Makoto; Spencer, Lisa A; Weller, Peter F

    2016-07-01

    The traditional paradigm of eosinophils as end-stage damaging cells has mainly relied on their release of cytotoxic proteins. Cytokine-induced cell survival and secretion of granular contents from tissue-dwelling eosinophil are thought to be important mechanisms for eosinophilic inflammatory disorders, although the occurrence of cytolysis and its products (i.e., free extracellular granules) has been observed in affected lesions. Recent evidence indicates that activated eosinophils can exhibit a non-apoptotic cell death pathway, namely extracellular trap cell death (ETosis) that mediates the eosinophil cytolytic degranulation. Here, we discuss the current concept of eosinophil ETosis which provides a new look at eosinophilic inflammation. Lessons from eosinophilic chronic rhinosinusitis revealed that ETosis-derived DNA traps, composed of stable web-like chromatin, contribute to the properties of highly viscous eosinophilic mucin and impairments in its clearance. Intact granules entrapped in DNA traps are causing long-lasting inflammation but also might have immunoregulatory roles. Eosinophils possess a way to have post-postmortem impacts on innate immunity, local immune response, sterile inflammation, and tissue damage. PMID:27393701

  8. Severe Aplastic Anemia Associated With Eosinophilic Fasciitis

    PubMed Central

    de Masson, Adèle; de Latour, Régis Peffault; Benhamou, Ygal; Moluçon-Chabrot, Cécile; Bay, Jacques-Olivier; Laquerrière, Annie; Picquenot, Jean-Michel; Michonneau, David; Leguy-Seguin, Vanessa; Rybojad, Michel; Bonnotte, Bernard; Jardin, Fabrice; Lévesque, Hervé; Bagot, Martine; Socié, Gérard

    2013-01-01

    Abstract Diffuse eosinophilic fasciitis (Shulman disease) is a rare sclerodermiform syndrome that, in most cases, resolves spontaneously or after corticosteroid therapy. It has been associated with hematologic disorders, such as aplastic anemia. The clinical features and long-term outcomes of patients with eosinophilic fasciitis and associated aplastic anemia have been poorly described. We report the cases of 4 patients with eosinophilic fasciitis and associated severe aplastic anemia. For 3 of these patients, aplastic anemia was refractory to conventional immunosuppressive therapy with antithymocyte globulin and cyclosporine. One of the patients received rituximab as a second-line therapy with significant efficacy for both the skin and hematologic symptoms. To our knowledge, this report is the first to describe rituximab used to treat eosinophilic fasciitis with associated aplastic anemia. In a literature review, we identified 19 additional cases of eosinophilic fasciitis and aplastic anemia. Compared to patients with isolated eosinophilic fasciitis, patients with eosinophilic fasciitis and associated aplastic anemia were more likely to be men (70%) and older (mean age, 56 yr; range, 18–71 yr). Corticosteroid-containing regimens improved skin symptoms in 5 (42%) of 12 cases but were ineffective in the treatment of associated aplastic anemia in all but 1 case. Aplastic anemia was profound in 13 cases (57%) and was the cause of death in 8 cases (35%). Only 5 patients (22%) achieved long-term remission (allogeneic hematopoietic stem cell transplantation: n = 2; cyclosporine-containing regimen: n = 2; high-dose corticosteroid-based regimen: n = 1). PMID:23429351

  9. Use of AN Eosinophil Specific Monoclonal Antibody in Assessing Eosinophil Function.

    NASA Astrophysics Data System (ADS)

    Minkoff, Marjorie Sue

    A monoclonal antibody to an eosinophil specific determinant is very important in assessing eosinophil function during helminthic infection. Eosinophils induced by Schistosoma mansoni infection in BALB/c mice were used to induce C57B1/6 immunocytes for production of hybridomas secreting eosinophil monoclonal antibodies. These antibodies were shown to react with an eosinophil surface epitope but not with neutrophils or macrophages as determined by ELISA, immunodiffusion, immunofluorescence, and immunoblot assay. Affinity chromatography with eosinophil chemotactic factor-sepharose consistently selected out a { rm M_ R} 67,000 protein from solubilized eosinophil membrane antigens but not from neutrophil and macrophage antigens. In vitro studies showed that the eosinophil-specific monoclonal antibodies abrogated antibody-dependent eosinophil -mediated killing of S. mansoni schistosomula using mouse, rat or human eosinophils. Neutrophil and macrophage killing activities were unaffected. The monoclonal antibodies effected complement-dependent lysis of mouse and rat eosinophils but not of human eosinophils. ECF-treated eosinophils showed enhanced killing of schistosomula which was blocked by the monoclonal antibody. Murine and human eosinophils preincubated with monoclonal antibody exhibited decreased chemotaxis to ECF at optimal chemotactic concentrations. The monoclonal antibody also blocked eosinophil binding to ECF- sepharose beads. In vivo induction of peripheral blood eosinophilia by injection of S. mansoni eggs was suppressed by injections of monoclonal antibodies 2CD13 and 2QD45 in mouse and rat experimental models. Eosinophilia induced by keyhole limpet hemocyanin- cyclophosphamide treatment was also suppressed by monoclonal antibody in both murine and rat systems. Pulmonary granulomas in mice given egg injection and monoclonal antibody were smaller and contained fewer eosinophils than those granulomas from mice given eggs only. In immuno-biochemical studies, the

  10. Medical therapy in eosinophilic oesophagitis.

    PubMed

    Straumann, Alex

    2015-10-01

    Eosinophilic oesophagitis (EoE) is a chronic-inflammatory disease of the oesophagus. If left untreated, eosinophilic inflammation induces fibrosis, angiogenesis and stricture formation, resulting finally in a so called remodelling with structural and functional damage of the organ. In addition, patients with untreated EoE are permanently at risk of experiencing food impactions. It is therefore widely accepted that active EoE should be treated. Any treatment applied in EoE should ideally achieve two therapeutic goals: first, resolution of symptoms, and, second, control of inflammation. Avoidance of food allergens by elimination diets as well as anti-inflammatory drugs have both the ability to achieve these goals. Among the pharmacological options, only corticosteroids have documented efficacy, whereas alternatives have shown rather disappointing results or are still under evaluation. Of note, swallowed topical corticosteroids are at least as efficient as systemically administered corticosteroids but have fewer side effects. As such topical corticosteroids are widely used as first-line drug in the treatment of EoE, even though this compound is currently not approved for this indication by regulatory authorities. Unfortunately, complete resolution of symptoms can be achieved with swallowed topical corticosteroids only in approximately 70% of patients despite appropriate dosing and despite correct administration of these compounds. Control of inflammation is even harder to achieve, as only in approximately 50% of patients tissue eosinophilia disappears completely under this anti-inflammatory medication. For this group of "difficult to treat" patients, therapeutic alternatives are urgently needed. Fortunately several anti-allergic drugs and several biologicals are currently under investigation. PMID:26552779

  11. Esophageal Microbiome in Eosinophilic Esophagitis

    PubMed Central

    Harris, J. Kirk; Fang, Rui; Wagner, Brandie D.; Choe, Ha Na; Kelly, Caleb J.; Schroeder, Shauna; Moore, Wendy; Stevens, Mark J.; Yeckes, Alyson; Amsden, Katie; Kagalwalla, Amir F.; Zalewski, Angelika; Hirano, Ikuo; Gonsalves, Nirmala; Henry, Lauren N.; Masterson, Joanne C.; Robertson, Charles E.; Leung, Donald Y.; Pace, Norman R.; Ackerman, Steven J.; Furuta, Glenn T.; Fillon, Sophie A.

    2015-01-01

    Objective The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis. Design In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease. Results Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects. Conclusions Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD. PMID:26020633

  12. Platelet-activating factor induces eosinophil peroxidase release from purified human eosinophils.

    PubMed Central

    Kroegel, C; Yukawa, T; Dent, G; Chanez, P; Chung, K F; Barnes, P J

    1988-01-01

    The degranulation response of purified human eosinophils to platelet-activating factor (PAF) has been studied. PAF induced release of eosinophil peroxidase (EPO) and beta-glucuronidase from highly purified human eosinophils with an EC50 of 0.9 nM. The order of release was comparable with that induced by phorbol myristate acetate (PMA). The new specific PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-H-thieno[3,2-f] [1,2,4]triazolo-[4,3a][1,4]-diazepin-2-yl](4-morpholinyl)- 1-propane-one (WEB 2086) inhibited the PAF-induced enzyme release by human eosinophils in a dose-dependent manner. The viability of eosinophils were unaffected both by PAF and WEB 2086. The results suggest that PAF may amplify allergic and inflammatory reactions by release of preformed proteins from eosinophil granules. PMID:3410498

  13. Eosinophilic follicular reaction induced by Demodex folliculorum mite: a different disease from eosinophilic folliculitis.

    PubMed

    Sabater-Marco, V; Escutia-Muñoz, B; Botella-Estrada, R

    2015-06-01

    Eosinophilic folliculitis (EF) is an idiopathic dermatitis included in the spectrum of eosinophilic pustular follicular reactions. Demodex folliculorum has been implicated as contributing to the pathogenesis of human immunodeficiency virus-associated EF, but it has not been described outside this context. We present an immunocompetent 65-year-old white man with a 5-year history of recurrent pruritic erythematous and oedematous lesions on his face, neck and scalp. Histopathologically, an eosinophilic microabcess with Demodex folliculorum mite within a pilosebaceous follicle was seen, and considered the causal agent. There were also accumulations of eosinophil granules on collagen bundles, and flame figure formations in the dermis. We believe that 'eosinophilic follicular reaction' is an appropriate term to describe this case of EF induced by D. folliculorum and thus distinguish it from the idiopathic form of EF. Moreover, this case suggests that D. folliculorum can sometimes induce an eosinophilic immune reaction. PMID:25623943

  14. Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation.

    PubMed

    Soragni, Alice; Yousefi, Shida; Stoeckle, Christina; Soriaga, Angela B; Sawaya, Michael R; Kozlowski, Evelyne; Schmid, Inès; Radonjic-Hoesli, Susanne; Boutet, Sebastien; Williams, Garth J; Messerschmidt, Marc; Seibert, M Marvin; Cascio, Duilio; Zatsepin, Nadia A; Burghammer, Manfred; Riekel, Christian; Colletier, Jacques-Philippe; Riek, Roland; Eisenberg, David S; Simon, Hans-Uwe

    2015-03-19

    Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1). How MBP-1 toxicity is controlled within the eosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly. PMID:25728769

  15. Toxicity of Eosinophil MBP Is Repressed by Intracellular Crystallization and Promoted by Extracellular Aggregation

    PubMed Central

    Soragni, Alice; Yousefi, Shida; Stoeckle, Christina; Soriaga, Angela B.; Sawaya, Michael R.; Kozlowski, Evelyne; Schmid, Inès; Radonjic-Hoesli, Susanne; Boutet, Sebastien; Williams, Garth J.; Messerschmidt, Marc; Seibert, M. Marvin; Cascio, Duilio; Zatsepin, Nadia A.; Burghammer, Manfred; Riekel, Christian; Colletier, Jacques-Philippe; Riek, Roland; Eisenberg, David; Simon, Hans-Uwe

    2016-01-01

    SUMMARY Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1). How MBP-1 toxicity is controlled within the eosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly. PMID:25728769

  16. Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

    PubMed Central

    Hirano, Ikuo; Aceves, Seema S.

    2014-01-01

    In eosinophilic esophagitis (EoE), remodeling changes are manifest histologically in both the epithelium as well as in the subepithelium where lamina propria (LP) fibrosis, expansion of the muscularis propria and increased vascularity occur. The major clinical symptoms and complications of EoE are largely consequences of esophageal remodeling. Important mediators of the process include IL-5, IL-13, TGFβ1, mast cells, fibroblasts and eosinophils. Methods to detect remodeling effects include upper endoscopy, histopathology, barium esophagram, endoscopic ultrasonography, esophageal manometry, and functional luminal imaging. These modalities provide evidence of organ dysfunction that include focal and diffuse esophageal strictures, expansion of the mucosa and subepithelium, esophageal motor abnormalities and reduced esophageal distensibility. Complications of food impaction and perforations of the esophageal wall have been associated with reduction in esophageal caliber and increased esophageal mural stiffness. The therapeutic benefits of topical corticosteroids and elimination diet therapy in resolving mucosal eosinophilic inflammation of the esophagus are evident. Available therapies, however, have demonstrated variable ability to reverse existing remodeling changes of the esophagus. Systemic therapies that include novel, targeted biologic agents have the potential of addressing subepithelial remodeling. Esophageal dilation remains a useful, adjunctive therapeutic maneuver in symptomatic adults with esophageal stricture. As novel treatments emerge, it is essential that therapeutic endpoints account for the fundamental contributions of esophageal remodeling to overall disease activity. PMID:24813517

  17. Biodegradation of Single-Walled Carbon Nanotubes by Eosinophil Peroxidase

    PubMed Central

    Andón, Fernando T.; Kapralov, Alexandr A.; Yanamala, Naveena; Feng, Weihong; Baygan, Arjang; Chambers, Benedict J.; Hultenby, Kjell; Ye, Fei; Toprak, Muhammet S.; Brandner, Birgit D.; Fornara, Andrea; Klein-Seetharaman, Judith; Kotchey, Gregg P.; Star, Alexander; Shvedova, Anna A.

    2014-01-01

    Eosinophil peroxidase (EPO) is one of the major oxidant-producing enzymes during inflammatory states in the human lung. The degradation of single-walled carbon nanotubes (SWCNTs) upon incubation with human EPO and H2O2 is reported. Biodegradation of SWCNTs is higher in the presence of NaBr, but neither EPO alone nor H2O2 alone caused the degradation of nanotubes. Molecular modeling reveals two binding sites for SWCNTs on EPO, one located at the proximal side (same side as the catalytic site) and the other on the distal side of EPO. The oxidized groups on SWCNTs in both cases are stabilized by electrostatic interactions with positively charged residues. Biodegradation of SWCNTs can also be executed in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. Biodegradation is proven by a range of methods including transmission electron microscopy, UV-visible-NIR spectroscopy, Raman spectroscopy, and confocal Raman imaging. Thus, human EPO (in vitro) and ex vivo activated eosinophils mediate biodegradation of SWCNTs: an observation that is relevant to pulmonary responses to these materials. PMID:23447468

  18. Imipenem/cilastatin-induced acute eosinophilic pneumonia.

    PubMed

    Foong, Kap Sum; Lee, Ashley; Pekez, Marijeta; Bin, Wei

    2016-01-01

    Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute eosinophilic pneumonia. In this study, we present a case of imipenem/cilastatin-induced acute eosinophilic pneumonia. The patient presented with fever, acute hypoxic respiratory distress, and diffuse ground-glass opacities on the chest CT a day after the initiation of imipenem/cilastatin. Patient also developed peripheral eosinophilia. A reinstitution of imipenem/cilastatin resulted in recurrence of the signs and symptoms. A bronchoscopy with bronchoalveolar lavage showed 780 nucleated cells/mm(3) with 15% eosinophil. The patient's clinical condition improved significantly after the discontinuation of imipenem/cilastatin therapy and the treatment with corticosteroid. PMID:26944380

  19. Eosinophilic gastroenteritis associated with systemic lupus erythematosus.

    PubMed

    Barbie, David A; Mangi, Abeel A; Lauwers, Gregory Y

    2004-01-01

    Eosinophilic gastroenteritis is an uncommon disease with an obscure etiology, although associations with allergy, the idiopathic hypereosinophilic syndrome, and connective tissue disease have been reported. We present the case of a 37-year-old woman with a history of idiopathic thrombocytopenic purpura who presented with refractory nausea, vomiting, and abdominal pain. Imaging studies were significant for bowel wall thickening and ascites, while laboratory studies revealed a positive antinuclear antibody (ANA), a positive anti-double stranded (DS) DNA antibody, low complement, and proteinuria. Exploratory laparotomy with gastric and small bowel biopsies established the diagnosis of eosinophilic gastroenteritis. In addition, the patient met clinical criteria for the diagnosis of systemic lupus erythematosus. Previous studies have described eosinophilic gastroenteritis in patients with scleroderma, polymyositis, or dermatomyositis. This is the first report to our knowledge of an individual with eosinophilic gastroenteritis and systemic lupus erythematosus. PMID:15492606

  20. Spectrum of surgical presentation of eosinophilic enteritis.

    PubMed

    Shetty, Spoorthy Sudhakar; Shetty, Charan Kishor

    2015-01-01

    Eosinophilic enteritis is a rare disorder presenting mostly with diarrhea, malabsorption, abdominal pain, weight loss, and hypersensitivity. Surgical manifestation of eosinophilic gastrointestinal disorders depends on the site and extent of involvement. In our case series of four patients two of them had ileocaecal masses with recurrent subacute intestinal obstruction with past history of intake of antitubercular drugs for 9 months. On histopathological examination both of them proved to have eosinophilic enterocolitis. Thus it is a clinical dilemma to differentiate between these two conditions. The other two patients presented as acute abdomen with perforation and intussusception. All four patients were treated surgically. Postoperatively they recovered well with no symptoms on one year follow-up. In Indian setup tuberculosis being rampant there may be under reporting or wrongly diagnosed cases of eosinophilic enteritis. Thus a strong clinical suspicion and awareness of this clinical entity are essential among surgical community. PMID:25960910

  1. Spectrum of Surgical Presentation of Eosinophilic Enteritis

    PubMed Central

    Shetty, Spoorthy Sudhakar; Shetty, Charan Kishor

    2015-01-01

    Eosinophilic enteritis is a rare disorder presenting mostly with diarrhea, malabsorption, abdominal pain, weight loss, and hypersensitivity. Surgical manifestation of eosinophilic gastrointestinal disorders depends on the site and extent of involvement. In our case series of four patients two of them had ileocaecal masses with recurrent subacute intestinal obstruction with past history of intake of antitubercular drugs for 9 months. On histopathological examination both of them proved to have eosinophilic enterocolitis. Thus it is a clinical dilemma to differentiate between these two conditions. The other two patients presented as acute abdomen with perforation and intussusception. All four patients were treated surgically. Postoperatively they recovered well with no symptoms on one year follow-up. In Indian setup tuberculosis being rampant there may be under reporting or wrongly diagnosed cases of eosinophilic enteritis. Thus a strong clinical suspicion and awareness of this clinical entity are essential among surgical community. PMID:25960910

  2. The eosinophil as a therapeutic target in asthma: beginning of the end, or end of the beginning?

    PubMed

    Adamko, Darryl; Odemuyiwa, Solomon Olawole; Moqbel, Redwan

    2003-06-01

    A major goal in asthma therapy is to reduce or prevent the inflammatory response associated with bronchial hyperresponsiveness, reversible airway obstruction and airway remodelling. However, because of the complex nature of the disease, a single target for such an ideal therapeutic approach remains elusive. To ensure a more rational design of anti-asthma drugs, recent investigations have attempted to elucidate the roles of inflammatory cellular components in asthma. Such studies have shown that eosinophilic infiltration is a prominent feature in the pathophysiology of asthma. Nonetheless, the role of the eosinophil in asthma has been questioned following recent human studies investigating the efficacy of a novel therapeutic strategy targeted at eosinophils. PMID:12810184

  3. Allergic mechanisms of Eosinophilic oesophagitis.

    PubMed

    Leung, John; Beukema, Koen Robert; Shen, Alice Hangzhou

    2015-10-01

    Eosinophilic oesophagitis (EoE) is characterized by oesophageal dysfunction and oesophageal eosinophilia refractory to proton-pump-inhibitor treatment. EoE is a food allergy, as elimination of food trigger(s) abrogates the disease, while trigger reintroduction causes recurrence. The allergic mechanism of EoE involves both IgE and non-IgE processes. There is a break in oral tolerance, the immune mechanism allowing enteric exposure to food and micro-organisms without causing deleterious immune responses. Changes in life-style, alterations in gut flora and use of antibiotics may be increasing disease prevalence. Mouse models of EoE and human studies revealed the role of regulatory T-cells and iNKT-cells in the pathogenesis. Th2-cytokines like IL-4, IL-5 and IL-13, and other cytokines like TGFβ and TSLP are involved, but perhaps no one cytokine is critically important for driving the disease. Control of EoE may require a pharmaceutical approach that blocks more than one target in the Th2-inflammatory pathway. PMID:26552770

  4. Human eosinophils regulate human lung- and skin-derived fibroblast properties in vitro: A role for transforming growth factor β (TGF-β)

    PubMed Central

    Levi-Schaffer, Francesca; Garbuzenko, Ekaterina; Rubin, Ann; Reich, Reuven; Pickholz, Dalia; Gillery, Philippe; Emonard, Herve; Nagler, Arnon; Maquart, Francois A. Xavier

    1999-01-01

    Eosinophils have been associated with fibrosis. To investigate their direct role in fibrosis, human peripheral blood eosinophil sonicate was added to human lung or dermal fibroblasts, and proliferation ([3H]thymidine) and collagen synthesis ([3H]proline) were evaluated. Proliferation was enhanced significantly in the monolayers in a dose-dependent manner. The activity of the eosinophil fibrogenic factor(s) remained unaltered when heated (56°C, 30 min). Supernatants of cultured eosinophils (20 min or 18 hr) also enhanced lung fibroblast proliferation, indicating that the preformed mitogenic factor(s) can be released both promptly and with a long kinetic. Eosinophils significantly decreased collagen production in lung fibroblasts while increasing it in dermal fibroblasts. However, eosinophils containing matrix metalloproteinase 9 (zymography) in latent form and tissue inhibitors of metalloproteinases 1 and 2 (reverse zymography) did not influence either fibroblast matrix metalloproteinases or tissue inhibitors of metalloproteinases. Eosinophil sonicate added to skin and lung fibroblasts in tridimensional collagen lattices significantly enhanced lattice contraction. Transforming growth factor β (TGF-β) is a major fibrogenic cytokine produced by eosinophils. Therefore, to assess its role, eosinophil sonicate was preincubated with anti-TGF-β neutralizing antibodies. This treatment partially inhibited proliferation of lung and collagen synthesis of dermal fibroblasts and suppressed the stimulation of lattice contraction, indicating the fibrogenic role of eosinophil-associated TGF-β. In conclusion, we have shown that eosinophils act as direct modulatory cells in fibroblast proliferation, collagen synthesis, and lattice contraction, in part, through TGF-β. These data corroborate the importance of eosinophils in skin and lung fibrosis. PMID:10449750

  5. Diagnostic Approach to Eosinophilic Renal Neoplasms

    PubMed Central

    Kryvenko, Oleksandr N.; Jorda, Merce; Argani, Pedram; Epstein, Jonathan I.

    2015-01-01

    Context Eosinophilic renal neoplasms include a spectrum of solid and papillary tumors ranging from indolent benign oncocytoma to highly aggressive malignancies. Recognition of the correct nature of the tumor, especially in biopsy specimens, is paramount for patient management. Objective To review the diagnostic approach to eosinophilic renal neoplasms with light microscopy and ancillary techniques. Data Sources Review of the published literature and personal experience. Conclusions The following tumors are in the differential diagnosis of oncocytic renal cell neoplasm: oncocytoma, chromophobe renal cell carcinoma (RCC), hybrid tumor, tubulocystic carcinoma, papillary RCC, clear cell RCC with predominant eosinophilic cell morphology, follicular thyroid-like RCC, hereditary leiomyomatosis–associated RCC, acquired cystic disease–associated RCC, rhabdoid RCC, microphthalmia transcription factor translocation RCC, epithelioid angiomyolipoma, and unclassified RCC. In low-grade nonpapillary eosinophilic neoplasms, distinction between oncocytoma and low-grade RCC mostly rests on histomorphology; however, cytokeratin 7 immunostain may be helpful. In high-grade nonpapillary lesions, there is more of a role for ancillary techniques, including immunohistochemistry for cytokeratin 7, CA9, CD10, racemase, HMB45, and Melan-A. In papillary eosinophilic neoplasms, it is important to distinguish sporadic type 2 papillary RCC from microphthalmia transcription factor translocation and hereditary leiomyomatosis–associated RCC. Histologic and cytologic features along with immunohistochemistry and fluorescence in situ hybridization tests for TFE3 (Xp11.2) and TFEB [t(6;11)] are reliable confirmatory tests. Eosinophilic epithelial neoplasms with architecture, cytology, and/or immunoprofile not qualifying for either of the established types of RCC should be classified as unclassified eosinophilic RCC and arbitrarily assigned a grade (low or high). PMID:25357116

  6. Novel Targeted Therapies for Eosinophil-Associated Diseases and Allergy

    PubMed Central

    Radonjic-Hoesli, Susanne; Valent, Peter; Klion, Amy D.; Wechsler, Michael E.; Simon, Hans-Uwe

    2016-01-01

    Eosinophil-associated diseases often present with life-threatening manifestations and/or chronic organ damage. Currently available therapeutic options are limited to a few drugs that often have to be prescribed on a life-long basis to keep eosinophil counts under control. In the last 10 years, treatment options and outcomes in patients with clonal eosinophilic and other eosinophilic disorders have improved substantially. Several new targeted therapies have emerged, addressing different aspects of eosinophil expansion and inflammation. In this review, we discuss available and currently tested agents, as well as new strategies and drug targets relevant to both primary and secondary eosinophilic diseases, including allergic disorders. PMID:25340931

  7. Nodules, eosinophilia, rheumatism, dermatitis and swelling (NERDS): a novel eosinophilic disorder.

    PubMed

    Butterfield, J H; Leiferman, K M; Gleich, G J

    1993-07-01

    This study presents the clinical and laboratory findings of a novel syndrome associated with eosinophilia. Two young women presented with marked eosinophilia, and large, non-tender compressible articular nodules arising from the tenosynovium of extensor tendons, dermatitis, episodic swelling of the hands and/or feet and pain in adjacent muscles and joints. Tissue specimens were examined by routine haematoxylin and eosin staining, immunofluorescent staining for eosinophil granule major basic protein (MBP) and rhodamine-avidin or tryptase staining for mast cells. Plasma levels of MBP and eosinophil-derived neurotoxin (EDN) were quantitated by immunoassay. The first patient presented in 1967 at the age of 20 and had, in addition to nodules and eosinophilia, dermographism, recurrent episcleritis and axillary urticaria. Biopsy of a nodule showed tenosynovitis with necrotizing granulomas, non-specific vasculitis, eosinophils and eosinophil degranulation as shown by extracellular deposition of eosinophil granule MBP. Her symptoms responded to low-dose, alternate-day prednisone and have remained quiescent over the past 15 yr. The second patient presented in 1990 at the age of 28 with generalized pruritic dermatitis for 15 yr, eosinophilia for 2 yr, subcutaneous nodules and non-limiting pain in several joints. Biopsy of a nodule showed chronic mild tenosynovitis, numerous eosinophils and extracellular deposition of MBP. She remains untreated. Serum IgE values and plasma levels of MBP and EDN were elevated in both patients; mast cells were numerous in their synovial tissue. Based on their clinical courses, these patients reveal the existence of a distinctive, relatively benign eosinophilic disorder with good long-term prognosis. PMID:8221258

  8. Interleukin-4 and RANTES expression in maturing eosinophils derived from human cord blood CD34+ progenitors

    PubMed Central

    Velazquez, J R; Lacy, P; Mahmudi-Azer, S; Bablitz, B; Milne, C D; Denburg, J A; Moqbel, R

    2000-01-01

    Eosinophils elaborate a number of proinflammatory mediators, including immunoregulatory cytokines and chemokines. Interleukin (IL)-4 and RANTES are important cytokines that have previously been shown to be expressed by mature eosinophils. We hypothesized that de novo synthesis of IL-4 and RANTES occurs in nascent eosinophils, leading to storage of newly produced proteins in crystalloid granule-like structures. Cytokine mRNA and protein expression were examined in cultured eosinophil colonies, which were derived from purified cord blood CD34+ cells and generated in semisolid media (methylcellulose) in the presence of recombinant human (rh)IL-3 and rhIL-5. Cytokine mRNA profiles were analysed by the reverse transcription–polymerase chain reaction (RT–PCR) to determine transcription of IL-4 and RANTES in cells on days 0, 7, 14, 21 and 28 of culture. The expression of translated cytokine products and granule major basic protein (MBP) was confirmed, from day 23 onwards, for colonies cultured in semisolid media, by immunofluorescent labelling and confocal laser-scanning microscopy (CLSM). We found that mRNA sequences encoding IL-4 and RANTES were expressed in freshly prepared, non-differentiated CD34+ cells. Furthermore, RANTES mRNA localized to carbol chromotrope 2R-positive colony cells, as assessed using in situ RT–PCR on day 21 of culture in semisolid media, and was found to gradually decrease (relative to β2-microglobulin) in rhIL-3- and rhIL-5-treated colony cells (comprising > 90% eosinophil-like cells) up to day 28. Immunoreactivity for IL-4 and RANTES co-localized with MBP in maturing colony eosinophils on day 23 of culture in semisolid media, as judged by CLSM. These results suggest that synthesis and storage of immunoregulatory cytokines, essential for processes associated with adaptive immunity, occurs in nascent eosinophils during their growth and differentiation. PMID:11106947

  9. Current Diagnostic and Therapeutic Aspects of Eosinophilic Myocarditis

    PubMed Central

    Kuchynka, Petr; Palecek, Tomas; Masek, Martin; Cerny, Vladimir; Lambert, Lukas; Vitkova, Ivana; Linhart, Ales

    2016-01-01

    Eosinophilic myocarditis (EM) represents a rare form of myocardial inflammation with very heterogeneous aetiology. In developed countries, the most prevalent causes of EM are hypersensitivity or allergic reactions, as well as hematological diseases leading to eosinophilia. The disease may have a variable clinical presentation, ranging from asymptomatic forms to life-threatening conditions. Most patients with EM have marked eosinophilia in peripheral blood. Endomyocardial biopsy needs to be performed in most cases in order to establish a definitive diagnosis of EM. The therapy depends on the underlying aetiology. Immunosuppressive therapy represents the treatment mainstay in the majority of EM forms. PMID:26885504

  10. [Drug induced eosinophilic pleural effusion].

    PubMed

    Vasilescu, Raluca

    2014-01-01

    The hypersensitivity reactions induced by drugs, some widely used, like central nervous system medication, can have various presentations. The lung is a frequent target for such events. We present the case of 40-year-old male patient, non-smoker, with infant encephalopaty, seizures since age of 6 with polimorphic crisis (mainly absences), with anticonvulsivant treatment since 2011 (carbamazepine, sodium valproate, levetiracetam), with no respiratory medical history. Current symptoms started two weeks before, with chest pain, dry cough. He received no antibiotics. Chest X-ray and thoracic CT scan (27 June 2013) showed a left pleral effusion. Left exploratory thoracocentesis extracted 20 ml reddish pleural fluid: eosinophilic exsudate (60%) with normal adenosin deaminase. He also presents moderate blood eosinophilia (13.7%-1780/mm3). Pulmonary infarction with secondary pleurisy, thoracic trauma, acute pancreatitis with secondary pleurisy were excluded. No Loeffler transient infiltrates were documented, serology for Toxocara is IgG positive (historical) and not significant for current episode, no symptoms suggestive for toxocarosis (characteristic to young children, patient had no liver enlargement etc.), no hidatidosis or trichinelosis were found. As an exclusion diagnosis, a hypersensitivity reaction to anticonvulsivant medication was considered (mentioned in literature) carbamazepine and sodium valproate (even if medication was taken for a longer time), with blood and pleural eosinophilia. Together with the neurologist, the mentioned drugs were stopped and he was started on lamotrigine 2 tb/day and levetiracetam 1 tb/day, well tolerated, no absences were noticed. Total remission of blood eosinophilia and partial remission of pleural effusion were noticed. Subsequent follow-ups confirm favourable evolution, with healing of pleurisy and normal blood cell count, which are stable at 7 months after changing anticonvulsivant treatment. PMID:25241560

  11. Does bee pollen cause to eosinophilic gastroenteropathy?

    PubMed Central

    Güç, Belgin Usta; Asilsoy, Suna; Canan, Oğuz; Kayaselçuk, Fazilet

    2015-01-01

    Bee pollen is given to children by mothers in order to strengthen their immune systems. There are no studies related with the side effects of bee polen in the literature. In this article, the literature was reviewed by presenting a case of allergic eosinophilic gastropathy related with bee polen. A 5-year old child was admitted due to abdominal pain. Edema was detected on the eyelids and pretibial region. In laboratory investigations, pathology was not detected in terms of hepatic and renal causes that would explain the protein loss of the patient diagnosed with hypoproteinemia and hypoalbuminemia. Urticaria was detected during the follow-up visit. When the history of the patient was deepened, it was learned that bee pollen was given to the patient every day. The total eosinophil count was found to be 1 800/mm3. Allergic gastroenteropathy was considered because of hypereosinophilia and severe abdominal pain and endoscopy was performed. Biopsy revealed abundant eosinophils in the whole gastric mucosa. A diagnosis of allergic eosinophilic gastropathy was made. Bee polen was discontinued. Abdominal pain and edema disappeared in five days. Four weeks later, the levels of serum albumin and total eosinophil returned to normal. PMID:26568697

  12. Does bee pollen cause to eosinophilic gastroenteropathy?

    PubMed

    Güç, Belgin Usta; Asilsoy, Suna; Canan, Oğuz; Kayaselçuk, Fazilet

    2015-09-01

    Bee pollen is given to children by mothers in order to strengthen their immune systems. There are no studies related with the side effects of bee polen in the literature. In this article, the literature was reviewed by presenting a case of allergic eosinophilic gastropathy related with bee polen. A 5-year old child was admitted due to abdominal pain. Edema was detected on the eyelids and pretibial region. In laboratory investigations, pathology was not detected in terms of hepatic and renal causes that would explain the protein loss of the patient diagnosed with hypoproteinemia and hypoalbuminemia. Urticaria was detected during the follow-up visit. When the history of the patient was deepened, it was learned that bee pollen was given to the patient every day. The total eosinophil count was found to be 1 800/mm(3). Allergic gastroenteropathy was considered because of hypereosinophilia and severe abdominal pain and endoscopy was performed. Biopsy revealed abundant eosinophils in the whole gastric mucosa. A diagnosis of allergic eosinophilic gastropathy was made. Bee polen was discontinued. Abdominal pain and edema disappeared in five days. Four weeks later, the levels of serum albumin and total eosinophil returned to normal. PMID:26568697

  13. Eosinophilic oesophagitis: a novel treatment using Montelukast

    PubMed Central

    Attwood, S E A; Lewis, C J; Bronder, C S; Morris, C D; Armstrong, G R; Whittam, J

    2003-01-01

    Background: Eosinophilic oesophagitis is a rarely diagnosed condition involving eosinophil infiltration of the oesophageal mucosa and creating significant symptoms of dysphagia. Failure to diagnose this disorder relates to reluctance to biopsy an apparently normal oesophagus. This is essential for histological diagnosis. To date, treatment success has been achieved only with corticosteroids. We describe here the use of an eosinophil stabilising agent Montelukast for the symptomatic relief of these patients. Patients and methods: Twelve patients have been identified with this condition in our unit since 1995, after thorough investigation of their dysphagia. We commenced eight of these patients on the leukotriene receptor antagonist Montelukast to symptomatically improve their swallowing while avoiding the use of long term corticosteroids. Results: Many of these patients had been previously misdiagnosed, and therefore inappropriately and unsuccessfully treated for an extensive period prior to referral to our unit. All patients were unresponsive to acid suppression therapy alone but showed improvement in their swallowing on Montelukast. Six of eight reported complete subjective improvement, five patients remaining completely asymptomatic on a maintenance regimen. Conclusions: Eosinophilic oesophagitis is a disease that is often misdiagnosed due to lack of awareness and reluctance of clinicians to biopsy an apparently normal oesophagus in dysphagic patients, and therefore obtain a histological diagnosis. Investigation of these patients adds further evidence to this condition being a separate pathological state from gastro-oesophageal reflux and eosinophilic enteritis. Montelukast has been found to be of significant help in the symptomatic control of these patients while avoiding long term corticosteroids use. PMID:12524397

  14. Eosinophilic esophagitis: an autoimmune esophageal disorder.

    PubMed

    Malhotra, Neha; Levine, Jeremiah

    2014-12-01

    Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal inflammatory disease associated with esophageal dysfunction resulting from severe inflammation. The incidence and prevalence of EoE have been increasing in the past decade; however, the reason for this increase is unclear. There is a chronic inflammatory infiltrate that is present in EoE which promotes inflammation, symptoms, and dysfunction. In addition to eosinophils, interleukin (IL)-5 expressing T cells, B cells, eotaxin-3, IL-13, and IgE-bearing mast cells are present in EoE and are thought to contribute to the disease process. Eosinophils are pro-inflammatory and modulate multiple aspects of the immune response. Eosinophils produce a wide range of inflammatory cytokines, chemokines, granulocyte-monocyte colony-stimulating factors, and tumor necrosis factors. Once activated, eosinophils release granule components, which are toxic to a variety of tissues. Transforming growth factor β1 is a pro-fibrotic molecule produced by epithelial and inflammatory cells, is overexpressed in EoE, and plays a role in esophageal remodeling. Fibrous remodeling in EoE could be associated with symptoms of dysphagia and may explain and predict future esophageal strictures and dysmotility. EoE is a complex disease involving multiple activation pathways, a large number of cells, and various inflammatory molecules. It, along with other atopic disease, is becoming increasingly prevalent and has an important genetic load and may represent as an immunological tolerance disorder of the GI tract. PMID:25499460

  15. New Insights into Eosinophilic Otitis Media.

    PubMed

    Kanazawa, Hiromi; Yoshida, Naohiro; Iino, Yukiko

    2015-12-01

    Eosinophilic otitis media (EOM) is a type of intractable otitis media that occurs mainly in patients with bronchial asthma (BA). In 2011, the diagnostic criteria for EOM were established. EOM is characterized by the presence of a highly viscous yellowish effusion containing eosinophils and immunoglobulin E (IgE), eosinophil chemoattractants, such as eosinophil cationic protein, interleukin-5, and eotaxin. Local sensitization against foreign agents such as fungi or bacteria (e.g., Staphylococcus aureus) may result in local IgE production in the middle ear and may be responsible for the severity of EOM. The clinical features of EOM closely resemble localized eosinophilic granulomatosis polyangiitis, therefore it is necessary to be vigilant to the symptoms of mononeuritis, polyneuritis, and skin purpura during diagnosis. Standard treatment for EOM is the instillation of triamcinolone acetonide into the mesotympanum. However, severe cases exhibiting strong inflammation and otorrhea are not easily controlled with antibiotics and/or corticosteroids. We proposed the introduction of a severity score to evaluate the severity of EOM. This score correlated with local IgE levels in middle ear effusion. Clinically, the risk factors associated with this severity score were body mass index, and the duration of bronchial asthma (from the onset of BA to the age of the first consultation of otitis media to our hospital). We emphasize that early diagnosis and adequate treatment are vital in preventing progressive and sudden hearing loss resulting from EOM. PMID:26546407

  16. Functional expression of IL-12 receptor by human eosinophils: IL-12 promotes eosinophil apoptosis.

    PubMed

    Nutku, E; Zhuang, Q; Soussi-Gounni, A; Aris, F; Mazer, B D; Hamid, Q

    2001-07-15

    In murine models of allergic inflammation, IL-12 has been shown to decrease tissue eosinophilia, but the underlying mechanisms are not known. We evaluated the expression of IL-12R and the effect of IL-12 on eosinophil survival. In situ hybridization demonstrated the presence of mRNA and immunoreactivity for IL-12Rbeta1 and -beta2 subunits in human peripheral blood eosinophils. Surface expression of IL-12Rbeta1 and -beta2 subunits on freshly isolated human eosinophils was optimally expressed after incubation with PMA. To determine the functional significance of IL-12R studies, we studied cell viability and apoptosis. Morphological analysis and propidium iodide staining for cell cycle demonstrated that recombinant human IL-12 increased in vitro human eosinophil apoptosis in a dose-dependent manner. Addition of IL-5 together with IL-12 abrogated eosinophil apoptosis, suggesting that IL-12 and IL-5 have antagonistic effects. Our findings provide evidence for a novel role for IL-12 in regulating eosinophil function by increasing eosinophil apoptosis. PMID:11441113

  17. [FEATURES OF TREATMENT OF EOSINOPHILIC ESOPHAGITIS IN SCHOOLCHILDREN].

    PubMed

    Horodylovska, M I

    2015-01-01

    The inclusion of probiotic L. reuteri into the complex therapy of eosinophilic esophagitis significantly affect the outcomes of children--there was significant decrease in the number of eosinophils in the esophageal mucosa of children. PMID:26118052

  18. SOCS3 Silencing Attenuates Eosinophil Functions in Asthma Patients

    PubMed Central

    Zafra, Mª Paz; Cañas, Jose A.; Mazzeo, Carla; Gámez, Cristina; Sanz, Veronica; Fernández-Nieto, Mar; Quirce, Santiago; Barranco, Pilar; Ruiz-Hornillos, Javier; Sastre, Joaquín; del Pozo, Victoria

    2015-01-01

    Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process. PMID:25764157

  19. SOCS3 silencing attenuates eosinophil functions in asthma patients.

    PubMed

    Zafra, Ma Paz; Cañas, Jose A; Mazzeo, Carla; Gámez, Cristina; Sanz, Veronica; Fernández-Nieto, Mar; Quirce, Santiago; Barranco, Pilar; Ruiz-Hornillos, Javier; Sastre, Joaquín; del Pozo, Victoria

    2015-01-01

    Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process. PMID:25764157

  20. Eosinophilic esophagitis: emerging therapies and future perspectives.

    PubMed

    Straumann, Alex

    2014-06-01

    Twenty years have passed since eosinophilic esophagitis was first recognized as a new and distinct entity. Current treatment modalities for eosinophilic esophagitis include the "3 Ds": drugs, allergen avoidance with diet, and esophageal dilation. Drugs entail the limitation that only corticosteroids have a proven efficacy; most other compounds evoke only a minimal effect. Diets must be maintained continuously and they interfere markedly with the quality of life, possibly even involving some risk of malnutrition. A greater understanding of the immunopathogenesis, natural history, and disease spectrum will inevitably lead to improved therapeutic outcomes for this emerging entity. PMID:24813523

  1. Eosinophilic pleural effusion complicating allergic bronchopulmonary aspergillosis.

    PubMed

    Kirschner, Austin N; Kuhlmann, Erica; Kuzniar, Tomasz J

    2011-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) is primarily a disease of patients with cystic fibrosis or asthma, who typically present with bronchial obstruction, fever, malaise, and expectoration of mucus plugs. We report a case of a young man with a history of asthma who presented with cough, left-sided pleuritic chest pain and was found to have lobar atelectasis and an eosinophilic, empyematous pleural effusion. Bronchoscopy and sputum cultures grew Aspergillus fumigatus, and testing confirmed strong allergic response to this mold, all consistent with a diagnosis of ABPA. This novel and unique presentation of ABPA expands on the differential diagnosis of eosinophilic pleural effusions. PMID:21311176

  2. [The eosinophilic otitis media's research progress].

    PubMed

    Liu, Yang; Zhang, Zhiyuan

    2015-09-01

    The eosinophilic otitis media(EOM) is an intractable disease characterized by the presence of a highly viscous yellow effusion with extensive accumulation of eosinophils in the middle ear; granulation tissue can been discovered in the middle ear cavity; most of patients have association with bronchial asthma; resist to conventional treatment for otitis media; EOM patients show gradual deterioration of hearing and sometimes become deaf suddenly; effective treatment involves use of topical and oral steroids. This article summarizes the progress of the EOM's diagnosis and treatment. PMID:26647553

  3. Invariant Natural Killer T cells in children with Eosinophilic Esophagitis

    PubMed Central

    Jyonouchi, Soma; Smith, Cara Lea; Saretta, Francesca; Abraham, Valsamma; Ruymann, Kathryn R; Modayur-Chandramouleeswaran, Prasanna; Wang, Mei-Lun; Spergel, Jonathan M.; Cianferoni, Antonella

    2013-01-01

    Background Eosinophilic esophagitis (EoE) is an atopic disease characterized by eosinophilic inflammation in which dietary antigens (in particular, milk) play a major role. EoE is most likely a mixed IgE and non-IgE food-mediated reaction in which over-expression of Th2 cytokines, particularly IL-13, play a major role; however, the cells responsible for IL-13 over-expression remain elusive. Th2-cytokines are secreted following the ligation of invariant natural killer T cell receptors to sphingolipids (SL). Sphingolipids (SL) are presented via the CD1d molecule on the INKT cell surface. Cow’s milk-derived SL has been shown to activate iNKTs from children with IgE-mediated food allergies to milk (FA-MA) to produce Th2 cytokines. The role of iNKTs and milk-SL in EoE pathogenesis is currently unknown. Objective To investigate the role of iNKTs and milk-SL in EoE. Methods Peripheral blood mononuclear cells (PBMCs) from 10 children with active EoE (EoE-A), 10 children with controlled EoE (EoE-C), and 16 healthy controls (Non-EoE) were measured ex-vivo and then incubated with α-galactosylceramide (αGal) and milk-SL. INKTs from peripheral blood (PB) and esophageal biopsies were studied. Results EoE-A-children had significantly fewer peripheral blood iNKTs with a greater Th2-response to αGal and milk-SM compared to iNKTs of EoE-C and Non-EoE children. Additionally, EoE-A children had increased iNKT levels in esophageal biopsies compared to EoE-C children. Conclusion Milk-SLs are able to activate peripheral blood iNKTs in EoE-A children to produce Th2 cytokines. Additionally, iNKT levels are higher at the site of active esophageal eosinophilic inflammation. Clinical Relevance This study suggests that sphingolipids (SL) contained in milk may drive the development of EoE by promoting an iNKT cell-mediated Th2-type cytokine response that facilitates eosinophil-mediated allergic inflammation. PMID:24118614

  4. Eosinophils in Gastrointestinal disorders- eosinophilic gastrointestinal diseases, celiac disease, inflammatory bowel diseases and parasitic infections

    PubMed Central

    Mehta, Pooja; Furuta, Glenn T.

    2015-01-01

    Synopsis The gastrointestinal tract provides an intriguing organ for considering the eosinophil’s role in health and disease. The normal gastrointestinal (GI) tract, except for the esophagus, is populated by eosinophils that are present throughout the mucosa in varying numbers. This latter fact raises the possibility that eosinophils participate in innate mechanisms of defense. In contrast, a number of clinical studies provide a wealth of data that associates increased numbers of eosinophils with inflammatory GI diseases; these findings prompt concerns that eosinophils may have a deleterious effect on the gut. In this article we present clinical features of 4 disease processes that have been associated with eosinophilia and suggest areas requiring investigation as to their clinical significance and scientific relevance. PMID:26209893

  5. Diagnostic and therapeutic strategies for eosinophilic esophagitis

    PubMed Central

    Zaidi, Asifa K; Mussarat, Ahad; Mishra, Anil

    2014-01-01

    Eosinophilic esophagitis (EoE) is a recently recognized allergic disorder, characterized by eosophageal dysfunction, accumulation of ≥15 eosinophils/high-powered field, eosinophil microabssess, basal cell hyperplasia, extracellular eosinophilic granules in the esophageal epithelial mucosal biopsy and a lack of response to a 8-week proton pump inhibitor treatment. Despite the increased incidences and considerable progress made in understanding EoE pathogenesis, there are limited diagnostic and therapeutic options available for EoE. Currently, the only criterion for diagnosing EoE is repetitive esophageal endoscopic biopsies and histopathological evaluation. Antigen elimination or corticosteroid therapies are effective therapies for EoE but are expensive and have limitations, if continued in the long term. Hence, there is a great necessity for novel noninvasive diagnostic biomarkers that can easily diagnose EoE and assess effectiveness of therapy. Herein, we have provided an update on key molecules involved in the disease initiation, and progression and proposed novel noninvasive diagnostic molecules and strategies for EoE therapy. PMID:25400904

  6. Eosinophilic esophagitis: asthma of the esophagus?

    PubMed

    Arora, Amindra S; Yamazaki, Kiyoshi

    2004-07-01

    Eosinophilic esophagitis (EE) is rapidly emerging as a distinct disease entity in both pediatric and adult gastroenterology. The typical clinical presentation includes solid food dysphagia in young men who have an atopic predisposition. Food impaction necessitating endoscopic intervention is common. EE should be suspected, in particular, in patients with unexplained dysphagia or those with no response to antacid or anti-acid secretory therapy. Careful endoscopic and radiographic examinations reveal furrows, corrugations, rings, whitish plaques, fragile crêpe paper-like appearance, and a small-caliber esophagus. Mucosal erosion in the distal esophagus, characteristic to reflux esophagitis, is absent in EE. Marked eosinophil infiltration in the esophageal epithelia (>20 eosinophils per high-power field) is the diagnostic hallmark. Food antigens and aeroallergens may play a role in the pathogenesis of EE. The mechanisms may be dependent or independent of immunoglobulin E. Elimination diets, systemic and topical corticosteroids, leukotriene receptor antagonists, and, most recently, an anti-interleukin-5 monoclonal antibody have been used to treat EE. EE likely represents another example of eosinophil-associated inflammation of epithelia at the interface between external and internal milieu, similar to bronchial asthma and atopic dermatitis. This review summarizes recent progress in the diagnosis and management of EE and discusses future research directions. PMID:15224275

  7. Origin, regulation and physiological function of intestinal eosinophils

    PubMed Central

    Fulkerson, Patricia C.; Rothenberg, Marc E.

    2009-01-01

    Eosinophils are pleiotropic multi-functional leukocytes that are typically associated with the initiation and propagation of inflammatory responses, particularly helminth infection and allergic disease. However, expanding evidence supports a broader role for eosinophils in homeostatic function and organ development and modulation of local immune responses via interaction with other effector cells. In this review, the biology of eosinophils in the healthy gut is summarized. In particular, the molecular steps involved in eosinophil development and trafficking are described, with special attention to the important role of the transcription factor GATA-1, the eosinophil selective cytokine IL-5 and the eotaxin subfamily of chemokines. In addition, the regulation of eosinophil survival by inhibitory and death receptors and the expanding role for eosinophils in health and disease are reviewed. PMID:18492563

  8. Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis

    PubMed Central

    Matthews, Stephen P.; McMillan, Sarah J.; Colbert, Jeff D.; Lawrence, Rachel A.; Watts, Colin

    2016-01-01

    Summary Eosinophils are now recognized as multifunctional leukocytes that provide critical homeostatic signals to maintain other immune cells and aid tissue repair. Paradoxically, eosinophils also express an armory of granule-localized toxins and hydrolases believed to contribute to pathology in inflammatory disease. How eosinophils deliver their supporting functions while avoiding self-inflicted injury is poorly understood. We have demonstrated that cystatin F (CF) is a critical survival factor for eosinophils. Eosinophils from CF null mice had reduced lifespan, reduced granularity, and disturbed granule morphology. In vitro, cysteine protease inhibitors restored granularity, demonstrating that control of cysteine protease activity by CF is critical for normal eosinophil development. CF null mice showed reduced pulmonary pathology in a model of allergic lung inflammation but also reduced ability to combat infection by the nematode Brugia malayi. These data identify CF as a “cytoprotectant” that promotes eosinophil survival and function by ensuring granule integrity. Video Abstract PMID:27067058

  9. Galectin-10, a Potential Biomarker of Eosinophilic Airway Inflammation

    PubMed Central

    Chua, Justin C.; Douglass, Jo A.; Gillman, Andrew; O'Hehir, Robyn E.; Meeusen, Els N.

    2012-01-01

    Measurement of eosinophilic airway inflammation can assist in the diagnosis of allergic asthma and in the management of exacerbations, however its clinical implementation remains difficult. Galectin-10 has been associated with eosinophilic inflammation and has the potential to be used as a surrogate biomarker. This study aimed to assess the relationship between galectin-10 in sputum with sputum eosinophil counts, the current gold standard of eosinophil inflammation in the lung. Thirty-eight sputum samples were processed for both eosinophil counts by cytospins and semi-quantitative measurements of galectin-10 by western blots. A strong association was observed between galectin-10 levels in sputum and sputum eosinophil measurements, and they accurately determined sputum eosinophilia. The results support the potential for galectin-10 to be used as a surrogate biomarker of eosinophilic airway inflammation. PMID:22880030

  10. Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils.

    PubMed

    Zhu, Xiang; Hogan, Simon P; Molkentin, Jeffery D; Zimmermann, Nives

    2016-04-15

    Eosinophil degranulation and clusters of free extracellular granules are frequently observed in diverse diseases, including atopic dermatitis, nasal polyposis, and eosinophilic esophagitis. Whether these intact granules are released by necrosis or a biochemically mediated cytolysis remains unknown. Recently, a peptidyl-prolyl isomerase located within the mitochondrial matrix, cyclophilin D (PPIF), was shown to regulate necrotic, but not apoptotic, cell death in vitro in fibroblasts, hepatocytes, and cardiomyocytes. Whether cyclophilin D regulates necrosis in hematopoietic cells such as eosinophils remains unknown. We used PPIF-deficient (Ppif(-/-)) mice to test whether cyclophilin D is required for regulating eosinophil necrosis. PPIF deficiency did not affect eosinophil development or maturation at baseline. After in vitro ionomycin or H2O2 treatment, Ppif(-/-) eosinophils were significantly protected from Ca(2+) overload- or oxidative stress-induced necrosis. Additionally, Ppif(-/-) eosinophils demonstrated significantly decreased necrosis, but not apoptosis, in response to Siglec-F cross-linking, a stimulus associated with eosinophil-mediated processes in vitro and in vivo. When treated with apoptosis inducers, Ppif(+/+) and Ppif(-/-) eosinophils exhibited no significant difference in apoptosis or secondary necrosis. Finally, in a dextran sodium sulfate-induced colitis model, although levels of colitogenic cytokines and eosinophil-selective chemokines were comparable between Ppif(+/+) and Ppif(-/-) mice, the latter exhibited decreased clinical outcomes. This correlated with significantly reduced eosinophil cytolysis in the colon. Collectively, our present studies demonstrate that murine eosinophil necrosis is regulated in vitro and in vivo by cyclophilin D, at least in part, thus providing new insight into the mechanism of eosinophil necrosis and release of free extracellular granules in eosinophil-associated diseases. PMID:26893161

  11. Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans

    PubMed Central

    Ueki, Shigeharu; Melo, Rossana C. N.; Ghiran, Ionita; Spencer, Lisa A.; Dvorak, Ann M.; Weller, Peter F.

    2013-01-01

    Eosinophils release their granule proteins extracellularly through exocytosis, piecemeal degranulation, or cytolytic degranulation. Findings in diverse human eosinophilic diseases of intact extracellular eosinophil granules, either free or clustered, indicate that eosinophil cytolysis occurs in vivo, but the mechanisms and consequences of lytic eosinophil degranulation are poorly understood. We demonstrate that activated human eosinophils can undergo extracellular DNA trap cell death (ETosis) that cytolytically releases free eosinophil granules. Eosinophil ETosis (EETosis), in response to immobilized immunoglobulins (IgG, IgA), cytokines with platelet activating factor, calcium ionophore, or phorbol myristate acetate, develops within 120 minutes in a reduced NADP (NADPH) oxidase-dependent manner. Initially, nuclear lobular formation is lost and some granules are released by budding off from the cell as plasma membrane–enveloped clusters. Following nuclear chromatolysis, plasma membrane lysis liberates DNA that forms weblike extracellular DNA nets and releases free intact granules. EETosis-released eosinophil granules, still retaining eosinophil cationic granule proteins, can be activated to secrete when stimulated with CC chemokine ligand 11 (eotaxin-1). Our results indicate that an active NADPH oxidase-dependent mechanism of cytolytic, nonapoptotic eosinophil death initiates nuclear chromatolysis that eventuates in the release of intact secretion-competent granules and the formation of extracellular DNA nets. PMID:23303825

  12. Eosinophilic Cholangitis—A Challenging Diagnosis of Benign Biliary Stricture

    PubMed Central

    Fragulidis, Georgios Panagiotis; Vezakis, Antonios I.; Kontis, Elissaios A.; Pantiora, Eirini V.; Stefanidis, Gerasimos G.; Politi, Aikaterini N.; Koutoulidis, Vasilios K.; Mela, Maria K.; Polydorou, Andreas A.

    2016-01-01

    Abstract When confronting a biliary stricture, both benign and malignant etiologies must be carefully considered as a variety of benign biliary strictures can masquerade as hilar cholangiocarcinoma (CCA). Therefore, patients could undergo a major surgery despite the possibility of a benign biliary disease. Approximately 15% to 24% of patients undergoing surgical resection for suspected biliary malignancy will have benign pathology. Eosinophilic cholangitis (EC) is a rare benign disorder of the biliary tract, which can cause obstructive jaundice and can pose a difficult diagnostic task. We present a rare case of a young woman who was referred to our hospital with obstructive painless jaundice due to a biliary stricture at the confluence of the hepatic bile ducts, with a provisional diagnosis of cholangiocarcinoma. Though, during her work up she was found to have EC, an extremely rare benign cause of biliary stricture, which is characterized by a dense eosinophilic infiltration of the biliary tree causing stricturing, fibrosis, and obstruction and which is reversible with short-term high-dose steroids. Despite its rarity, EC should be taken into consideration when imaging modalities demonstrate a biliary stricture, especially if preoperative diagnosis of malignancy cannot be made, in the setting of peripheral eosinophilia and the absence of cardinal symptoms of malignancy. PMID:26735539

  13. IL-5 in post-traumatic eosinophilic pleural effusion.

    PubMed Central

    Schandené, L; Namias, B; Crusiaux, A; Lybin, M; Devos, R; Velu, T; Capel, P; Bellens, R; Goldman, M

    1993-01-01

    Thoracic trauma or pneumothorax can result in pleural fluid eosinophilia. In this study we investigated the role of the eosinophilopoietic cytokine IL-5 in three cases of post-traumatic eosinophilic pleural effusions (EPE). Using a specific immunoenzymatic assay, significant levels of IL-5 were found in EPE (range 100-3000 pg/ml), while IL-5 was undetectable (< 25 pg/ml) in corresponding serum samples and in non-eosinophilic pleural fluids. IL-5 present in pleural fluids was found bioactive in a proliferative assay using a mouse CTLL-2 cell line transfected with the cDNA corresponding to the alpha chain of the human IL-5 receptor. Using a reverse polymerase chain reaction (PCR) method, we found IL-5 mRNA expression within pleural mononuclear cells from patients with EPE, but not in corresponding peripheral blood mononuclear cells (PBMC), confirming that IL-5 is synthesized locally in the pleural cavity. In the two cases in which pleural CD4+ cells were purified, these cells were identified as the major source of IL-5. Taken together, these data indicate that the development of post-traumatic EPE is related to a local secretion of IL-5 by CD4+ cells present in the pleural cavity. Images Fig. 1 PMID:8100745

  14. RNA Seq profiling reveals a novel expression pattern of TGF-β target genes in human blood eosinophils.

    PubMed

    Shen, Zhong-Jian; Hu, Jie; Esnault, Stephane; Dozmorov, Igor; Malter, James S

    2015-09-01

    Despite major advances in our understanding of TGF-β signaling in multiple cell types, little is known about the direct target genes of this pathway in human eosinophils. These cells constitute the major inflammatory component present in the sputum and lung of active asthmatics and their numbers correlate well with disease severity. During the transition from acute to chronic asthma, TGF-β levels rise several fold in the lung which drives fibroblasts to produce extracellular matrix (ECM) and participate in airway and parenchymal remodeling. In this report, we use purified blood eosinophils from healthy donors and analyze baseline and TGF-β responsive genes by RNA Seq, and demonstrate that eosinophils (PBE) express 7981 protein-coding genes of which 178 genes are up-regulated and 199 genes are down-regulated by TGF-β. While 18 target genes have been previously associated with asthma and eosinophilic disorders, the vast majority have been implicated in cell death and survival, differentiation, and cellular function. Ingenuity pathway analysis revealed that 126 canonical pathways are activated by TGF-β including iNOS, TREM1, p53, IL-8 and IL-10 signaling. As TGF-β is an important cytokine for eosinophil function and survival, and pulmonary inflammation and fibrosis, our results represent a significant step toward the identification of novel TGF-β responsive genes and provide a potential therapeutic opportunity by selectively targeting relevant genes and pathways. PMID:26112417

  15. Successful treatment of eosinophilic cellulitis with dapsone.

    PubMed

    Coelho de Sousa, Virgínia; Laureano Oliveira, André; Cardoso, Jorge

    2016-01-01

    A 55-year-old woman presented with a 3-year history of recurrent episodes of pruritic cellulitis-like erythematous plaques, mostly located on the limbs. Simultaneously, fever, malaise and peripheral eosinophilia were noted. The clinical diagnosis of eosinophilic cellulitis (also known as Well's syndrome) was supported by the histopathological finding of typical "flame figures". Treatment with dapsone was initiated at a dose of 50 mg per day. After one year of follow-up the patient was relapse-free. Eosinophilic cellulitis is an uncommon, recurrent inflammatory skin disease. The management is often a challenge, due to the frequent need for long-term therapy. Dapsone is an effective and safe treatment option. PMID:27617724

  16. GWAS identifies four novel eosinophilic esophagitis loci

    PubMed Central

    Sleiman, Patrick MA; Wang, Mei-Lun; Cianferoni, Antonella; Aceves, Seema; Gonsalves, Nirmala; Nadeau, Kari; Bredenoord, Albert J.; Furuta, Glenn T.; Spergel, Jonathan M.; Hakonarson, Hakon

    2014-01-01

    Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the esophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which have been previously associated with both atopic and autoimmune disease, and two EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly enriched in the esophagus. The identification of five EoE loci, not only expands our etiological understanding of the disease but may also represent new therapeutic targets to treat the most debilitating aspect of EoE, esophageal inflammation and remodeling. PMID:25407941

  17. Mepolizumab: A Review in Eosinophilic Asthma.

    PubMed

    Deeks, Emma D

    2016-08-01

    Mepolizumab (Nucala(®)) is a humanized monoclonal antibody against interleukin-5, a cytokine involved in the development, recruitment and activation of eosinophils (cellular mediators of airway inflammation, hyper-responsiveness and tissue remodelling). The drug is indicated as an add-on treatment for severe eosinophilic asthma, on the basis of its clinical benefit in this setting in the placebo-controlled DREAM, MENSA and SIRIUS trials. Based on the 52-week, phase II, DREAM study (which assessed varying intravenous mepolizumab dosages), intravenous mepolizumab 75 mg every 4 weeks (q4w) and the corresponding (recommended) subcutaneous dosage of 100 mg q4w were studied in the 32- and 24-week phase III MENSA and SIRIUS trials. In patients aged ≥12 years with severe eosinophilic asthma in the phase III studies, adding subcutaneous mepolizumab 100 mg q4w to current asthma therapy significantly reduced the rate of clinically relevant asthma exacerbations and, in those dependent on oral glucocorticoids (OCSs) for asthma control, enabled the daily OCS dose to be significantly reduced, relative to adding placebo. This mepolizumab regimen also significantly improved asthma control, health-related quality of life and (in one of the two studies) lung function, and had acceptable tolerability (with headache the most common adverse event). In the MENSA and SIRIUS extension, COSMOS, mepolizumab provided durable clinical benefit over up to 84 weeks' therapy with no new tolerability concerns. Thus, mepolizumab is a valuable add-on treatment option for adults and adolescents aged ≥12 years who have severe eosinophilic asthma despite optimized standard therapies. PMID:27311938

  18. Mechanisms of Disease of Eosinophilic Esophagitis.

    PubMed

    Davis, Benjamin P; Rothenberg, Marc E

    2016-05-23

    Eosinophilic esophagitis (EoE) is a recently recognized inflammatory disease of the esophagus with clinical symptoms derived from esophageal dysfunction. The etiology of EoE is now being elucidated, and food hypersensitivity is emerging as the central cornerstone of disease pathogenesis. Herein, we present a thorough picture of the current clinical, pathologic, and molecular understanding of the disease with a focus on disease mechanisms. PMID:26925500

  19. A spectrum of hypereosinophilic syndromes exemplified by six cats with eosinophilic enteritis.

    PubMed

    Hendrick, M

    1981-03-01

    Of six cats with eosinophilic enteritis, two had lesions confined to the intestinal tract, and four had varied disseminated eosinophilic infiltration of other organs. The lesions in these cats are similar to those of the hypereosinophilic syndrome in man. A feline hypereosinophilic syndrome is proposed, consisting of eosinophilic enteritis, disseminated eosinophilic disease, and eosinophilic leukemia. PMID:7467078

  20. Eosinophilic oesophagitis: clinical presentation and pathogenesis

    PubMed Central

    Bystrom, Jonas; O'Shea, Nuala R

    2014-01-01

    Eosinophilic oesophagitis (EoE) is an inflammatory disorder of the oesophagus which has become increasingly recognised over recent years, although it remains underdiagnosed in many centres. It is characterised histologically by a significant eosinophilic infiltration of the oesophageal mucosa (>15 eosinophils per high powered field), and clinically with features of oesophageal dysfunction such a dysphagia, food impaction, and proton pump inhibitor (PPI) resistant dyspepsia. Fibrosis and oesophageal remodelling may occur and lead to oesophageal strictures. An allergic predisposition is common in the EoE population, which appears to be primarily food antigen driven in children and aeroallergen driven in adults. Evidence suggests that the pathogenesis of EoE is due to a dysregulated immunological response to an environmental allergen, resulting in a T helper type 2 (Th2) inflammatory disease and remodelling of the oesophagus in genetically susceptible individuals. Allergen elimination and anti-inflammatory therapy with corticosteroids are currently the mainstay of treatment; however, an increasing number of studies are now focused on targeting different stages in the disease pathogenesis. A greater understanding of the underlying mechanisms resulting in EoE will allow us to improve the therapeutic options available. PMID:24647582

  1. Further characterization of human eosinophil peroxidase.

    PubMed Central

    Olsen, R L; Syse, K; Little, C; Christensen, T B

    1985-01-01

    The large and the small subunits (Mr 50 000 and 10 500 respectively) of human eosinophil peroxidase were isolated by gel filtration under reducing conditions. The subunits were very strongly associated but not apparently cross-linked by disulphide bridges. During storage, the large subunit tended to form aggregates, which required reduction to dissociate them. Amino acid analysis of the performic acid-treated large subunit showed the presence of 19 cysteic acid residues. The small subunit of eosinophil peroxidase had the same Mr value as the small subunit of myeloperoxidase. However, although these subunits have very similar amino acid compositions, they showed different patterns of peptide fragmentation after CNBr treatment. The carbohydrate of eosinophil peroxidase seemed associated exclusively with the large subunit and comprised mannose (4.5%, w/w) and N-acetylglucosamine (0.8%, w/w). The far-u.v.c.d. spectrum of the enzyme indicated the presence of relatively little ordered secondary structure. Images Fig. 3. PMID:4052025

  2. Eosinophilic Angiocentric Fibrosis of the Nasal Septum

    PubMed Central

    Li, Yunchuan; Liu, Honggang; Zang, Hongrui; Wang, Tong; Hu, Bin

    2013-01-01

    Background. Eosinophilic angiocentric fibrosis (EAF) is a rare benign condition of unknown aetiology that causes stenosis of the upper respiratory tract. It is most commonly found at the nasal septum and sinus mucosa causing mucosal thickening and nasal obstructive symptoms. The diagnosis is mainly based on characteristic histologic findings. Case Report. A 27-year-old young woman presented with a slow growing mass at her anterior nasal septum for over eight years. She complained of persistent nasal obstruction, epistaxis, sometimes diffused facial pain, and chronic headache. 3 years ago, the tumor was partially resected for ventilation and a nasal septum perforation was left. Imaging findings indicated soft-tissue thickening of the anterior part of septum and adjacent lateral nasal walls. Pathological examination showed numerous inflammatory cells infiltrates containing eosinophils, fibroinflammatory lesion with a whorled appearance fibrosis which typically surrounded vessels. A diagnosis of eosinophilic angiocentric fibrosis was made. All laboratory tests were unremarkable. Skin prick test was positive. The tumor-like lesion was totally resected. Conclusions. EAF is a rare benign and progressive disorder causing destruction. Combined with radiological imaging of EAF historical findings contribute to the diagnosis. It is important to prevent tumor from recurrence by total resection of the lesion. PMID:23634315

  3. Th2 and eosinophil responses suppress inflammatory arthritis

    PubMed Central

    Chen, Zhu; Andreev, Darja; Oeser, Katharina; Krljanac, Branislav; Hueber, Axel; Kleyer, Arnd; Voehringer, David; Schett, Georg; Bozec, Aline

    2016-01-01

    Th2–eosinophil immune responses are well known for mediating host defence against helminths. Herein we describe a function of Th2–eosinophil responses in counteracting the development of arthritis. In two independent models of arthritis, Nippostrongylus brasiliensis infection leads to Th2 and eosinophil accumulation in the joints associated with robust inhibition of arthritis and protection from bone loss. Mechanistically, this protective effect is dependent on IL-4/IL-13-induced STAT6 pathway. Furthermore, we show that eosinophils play a central role in the modulation of arthritis probably through the increase of anti-inflammatory macrophages into arthritic joints. The presence of these pathways in human disease is confirmed by detection of GATA3-positive cells and eosinophils in the joints of rheumatoid arthritis patients. Taken together, these results demonstrate that eosinophils and helminth-induced activation of the Th2 pathway axis effectively mitigate the course of inflammatory arthritis. PMID:27273006

  4. Th2 and eosinophil responses suppress inflammatory arthritis.

    PubMed

    Chen, Zhu; Andreev, Darja; Oeser, Katharina; Krljanac, Branislav; Hueber, Axel; Kleyer, Arnd; Voehringer, David; Schett, Georg; Bozec, Aline

    2016-01-01

    Th2-eosinophil immune responses are well known for mediating host defence against helminths. Herein we describe a function of Th2-eosinophil responses in counteracting the development of arthritis. In two independent models of arthritis, Nippostrongylus brasiliensis infection leads to Th2 and eosinophil accumulation in the joints associated with robust inhibition of arthritis and protection from bone loss. Mechanistically, this protective effect is dependent on IL-4/IL-13-induced STAT6 pathway. Furthermore, we show that eosinophils play a central role in the modulation of arthritis probably through the increase of anti-inflammatory macrophages into arthritic joints. The presence of these pathways in human disease is confirmed by detection of GATA3-positive cells and eosinophils in the joints of rheumatoid arthritis patients. Taken together, these results demonstrate that eosinophils and helminth-induced activation of the Th2 pathway axis effectively mitigate the course of inflammatory arthritis. PMID:27273006

  5. Eosinophilic esophagitis and food impaction: an instructive case.

    PubMed

    Tilakaratne, Samantha; Day, Andrew; Lemberg, Daniel

    2012-06-01

    Although the key features of eosinophilic esophagitis have been increasingly described over recent years, this entity is still often not considered and consequently diagnosis is often either not made or delayed. Typical endoscopic findings may be present. The diagnosis of eosinophilic esophagitis, however, relies on the histological assessment of mucosal biopsies. This case report highlights a common pattern of presentation of eosinophilic esophagitis and demonstrates the importance of considering this diagnosis. PMID:22798122

  6. Eosinophilic myositis in a slaughtered Korean native cattle

    PubMed Central

    Do, Sun Hee; Jeong, Da-Hee; Chung, Jae-Yong; Park, Jin-Kyu; Yang, Hai-Jie; Yuan, Dong-Wei

    2008-01-01

    Histopathological findings of eosinophilic myositis in the carcass of a slaughtered Korean native cow are presented. Lesions contained massive fibrous septae with vacuolar changes in some lesions, and the hypercontraction and rupturing of muscle bundles, with replacement by eosinophils. Necrosis and severe eosinophil infiltration were observed. Sarcoplasmic fragmentation and atrophy developed. Typical of granuloma, calcified myofibers were focally surrounded by macrophages and numerous inflammatory cells, and multinucleated giant cell formation was evident. PMID:19043319

  7. Cyclin-dependent kinase 5 regulates degranulation in human eosinophils.

    PubMed

    Odemuyiwa, Solomon O; Ilarraza, Ramses; Davoine, Francis; Logan, Michael R; Shayeganpour, Anooshirvan; Wu, Yingqi; Majaesic, Carina; Adamko, Darryl J; Moqbel, Redwan; Lacy, Paige

    2015-04-01

    Degranulation from eosinophils in response to secretagogue stimulation is a regulated process that involves exocytosis of granule proteins through specific signalling pathways. One potential pathway is dependent on cyclin-dependent kinase 5 (Cdk5) and its effector molecules, p35 and p39, which play a central role in neuronal cell exocytosis by phosphorylating Munc18, a regulator of SNARE binding. Emerging evidence suggests a role for Cdk5 in exocytosis in immune cells, although its role in eosinophils is not known. We sought to examine the expression of Cdk5 and its activators in human eosinophils, and to assess the role of Cdk5 in eosinophil degranulation. We used freshly isolated human eosinophils and analysed the expression of Cdk5, p35, p39 and Munc18c by Western blot, RT-PCR, flow cytometry and immunoprecipitation. Cdk5 kinase activity was determined following eosinophil activation. Cdk5 inhibitors were used (roscovitine, AT7519 and small interfering RNA) to determine its role in eosinophil peroxidase (EPX) secretion. Cdk5 was expressed in association with Munc18c, p35 and p39, and phosphorylated following human eosinophil activation with eotaxin/CCL11, platelet-activating factor, and secretory IgA-Sepharose. Cdk5 inhibitors (roscovitine, AT7519) reduced EPX release when cells were stimulated by PMA or secretory IgA. In assays using small interfering RNA knock-down of Cdk5 expression in human eosinophils, we observed inhibition of EPX release. Our findings suggest that in activated eosinophils, Cdk5 is phosphorylated and binds to Munc18c, resulting in Munc18c release from syntaxin-4, allowing SNARE binding and vesicle fusion, with subsequent eosinophil degranulation. Our work identifies a novel role for Cdk5 in eosinophil mediator release by agonist-induced degranulation. PMID:25346443

  8. A quantitative study of eosinophil polymorphs in Hodgkin's disease.

    PubMed

    Fuggle, W J; Crocker, J; Smith, P J

    1984-03-01

    Eosinophil polymorphonuclear leucocytes (polymorphs) were counted in 45 specimens from patients with Hodgkin's disease and five specimens from patients with reactive follicular hyperplasia. The use of chlorazol fast pink BK, a little known stain for eosinophil polymorphs, combined with image analysis facilitated rapid and reliable counting. Significant differences were found between the mean percentages of eosinophil polymorphs in the Rye subtypes of Hodgkin's disease. The numbers of eosinophil polymorphs in specimens from patients with reactive follicular hyperplasia were very low and could not be counted. PMID:6699190

  9. Monitoring nasal allergic inflammation by measuring the concentration of eosinophil cationic protein and eosinophils in nasal secretions.

    PubMed

    Wang, D; Clement, P; Smitz, J; de Waele, M; Derde, M P

    1995-02-01

    Quantitative measurement of the eosinophil cationic protein (ECP) concentration and the percentage of eosinophils in nasal secretions has greatly improved our understanding of the inflammatory process after natural allergen exposure. ECP and eosinophils were measured in the nasal secretions of 40 symptomatic patients with seasonal allergic rhinitis during the pollen season. Results showed a significant relationship between a high concentration of ECP (median: 410 ng/g, range: 6-2380 ng/g) and a high percentage of eosinophils (median: 13.5%, range: 1-85%). This quantitative study again demonstrated that infiltration by eosinophils and release of ECP play a key role in allergic rhinitis. It also suggests that the combined measurement of the percentage of eosinophils together with the ECP concentration in nasal secretions seems to be a very useful model in monitoring and assessing the condition of chronic nasal inflammation in patients with allergic rhinitis. PMID:7604937

  10. Role of P2 Receptors as Modulators of Rat Eosinophil Recruitment in Allergic Inflammation

    PubMed Central

    Alberto, Anael Viana Pinto; Faria, Robson Xavier; de Menezes, Joao Ricardo Lacerda; Surrage, Andrea; da Rocha, Natasha Cristina; Ferreira, Leonardo Gomes Braga; Frutuoso, Valber da Silva; Martins, Marco Aurélio; Alves, Luiz Anastácio

    2016-01-01

    ATP and other nucleotides are released from cells through regulated pathways or following the loss of plasma membrane integrity. Once outside the cell, these compounds can activate P2 receptors: P2X ionotropic receptors and G protein-coupled P2Y receptors. Eosinophils represent major effector cells in the allergic inflammatory response and they are, in fact, associated with several physiological and pathological processes. Here we investigate the expression of P2 receptors and roles of those receptors in murine eosinophils. In this context, our first step was to investigate the expression and functionality of the P2X receptors by patch clamping, our results showed a potency ranking order of ATP>ATPγS> 2meSATP> ADP> αβmeATP> βγmeATP>BzATP> UTP> UDP>cAMP. This data suggest the presence of P2X1, P2X2 and P2X7. Next we evaluate by microfluorimetry the expression of P2Y receptors, our results based in the ranking order of potency (UTP>ATPγS> ATP > UDP> ADP >2meSATP > αβmeATP) suggests the presence of P2Y2, P2Y4, P2Y6 and P2Y11. Moreover, we confirmed our findings by immunofluorescence assays. We also did chemotaxis assays to verify whether nucleotides could induce migration. After 1 or 2 hours of incubation, ATP increased migration of eosinophils, as well as ATPγS, a less hydrolysable analogue of ATP, while suramin a P2 blocker abolished migration. In keeping with this idea, we tested whether these receptors are implicated in the migration of eosinophils to an inflammation site in vivo, using a model of rat allergic pleurisy. In fact, migration of eosinophils has increased when ATP or ATPγS were applied in the pleural cavity, and once more suramin blocked this effect. We have demonstrated that rat eosinophils express P2X and P2Y receptors. In addition, the activation of P2 receptors can increase migration of eosinophils in vitro and in vivo, an effect blocked by suramin. PMID:26784445

  11. Prevalence of eosinophilic oesophagitis in adults presenting with oesophageal food bolus obstruction

    PubMed Central

    Heerasing, Neel; Lee, Shok Yin; Alexander, Sina; Dowling, Damian

    2015-01-01

    AIM: To look at the relationship between eosinophilic oesophagitis (EO) and food bolus impaction in adults. METHODS: We retrospectively analysed medical records of 100 consecutive patients who presented to our hospital with oesophageal food bolus obstruction (FBO) between 2012 and 2014. In this cohort, 96 were adults (64% male), and 4 paediatric patients were excluded from the analysis as our centre did not have paediatric gastroenterologists. Eighty-five adult patients underwent emergency gastroscopy. The food bolus was either advanced into the stomach using the push technique or retrieved using a standard retrieval net. Biopsies were obtained in 51 patients from the proximal and distal parts of the oesophagus at initial gastroscopy. All biopsy specimens were assessed and reviewed by dedicated gastrointestinal pathologists at the Department of Pathology, University Hospital Geelong. The diagnosis of EO was defined and established by the presence of the following histological features: (1) peak eosinophil counts > 20/hpf; (2) eosinophil microabscess; (3) superficial layering of eosinophils; (4) extracellular eosinophil granules; (5) basal cell hyperplasia; (6) dilated intercellular spaces; and (7) subepithelial or lamina propria fibrosis. The histology results of the biopsy specimens were accessed from the pathology database of the hospital and recorded for analysis. RESULTS: Our cohort had a median age of 60. Seventeen/51 (33%) patients had evidence of EO on biopsy findings. The majority of patients with EO were male (71%). Classical endoscopic features of oesophageal rings, furrows or white plaques and exudates were found in 59% of patients with EO. Previous episodes of FBO were present in 12/17 patients and 41% had a history of eczema, hay fever or asthma. Reflux oesophagitis and benign strictures were found in 20/34 patients who did not have biopsies. CONCLUSION: EO is present in approximately one third of patients who are admitted with FBO. Biopsies should be

  12. Eosinophilic esophagitis in adults: An update

    PubMed Central

    Ahmed, Monjur

    2016-01-01

    Eosinophilic esophagitis is a worldwide chronic allergic disease of the esophagus. In the last decade, there is an epidemic of this entity in the western world. Mostly seen in children and young adults, patients present with dysphagia or food impaction in the emergency room. Characteristic endoscopic findings, esophageal eosinophilia and non-responsiveness to proton pump inhibitors help make the diagnosis. Avoidance of food allergens, administration of steroidal anti-inflammatory medications and dilation of the esophagus are the mainstays of treatment. Investigations are ongoing for mucosal healing and optimum maintenance treatment. PMID:27158535

  13. Eosinophilic esophagitis in adults: An update.

    PubMed

    Ahmed, Monjur

    2016-05-01

    Eosinophilic esophagitis is a worldwide chronic allergic disease of the esophagus. In the last decade, there is an epidemic of this entity in the western world. Mostly seen in children and young adults, patients present with dysphagia or food impaction in the emergency room. Characteristic endoscopic findings, esophageal eosinophilia and non-responsiveness to proton pump inhibitors help make the diagnosis. Avoidance of food allergens, administration of steroidal anti-inflammatory medications and dilation of the esophagus are the mainstays of treatment. Investigations are ongoing for mucosal healing and optimum maintenance treatment. PMID:27158535

  14. Eosinophilic density in graft biopsies positive for rejection and blood eosinophil count can predict development of post-transplant digestive tract eosinophilia.

    PubMed

    Bush, Jonathan W; Mohammad, Saeed; Melin-Aldana, Hector; Kagalwalla, Amir F; Arva, Nicoleta C

    2016-06-01

    EGID is a known post-transplant complication. Its etiology has been related to antirejection medication, but other factors may also play a role as only few transplant recipients develop EGID despite standardized treatment. This study aimed to determine whether EGID is associated with rejection events and with a specific phenotype of the rejection-positive graft biopsies in children with solid organ transplant. All patients with liver, heart, and kidney transplant followed at our institution were included in the study. Digestive tract eosinophilia was more common in heart and liver recipients and was a rare event after renal transplantation. Subjects with EGID had higher incidence of rejection and elevated peripheral blood AEC. The first rejection event and high AEC values preceded EGID diagnosis in the majority of patients. Histologically, the initial rejection-positive graft biopsy revealed accentuated eosinophilia in EGID patients compared with non-EGID cohort, which correlated with higher blood eosinophil counts at the time of first rejection episode. Prominent graft tissue and peripheral blood eosinophilia prior to EGID diagnosis suggests a predisposition for eosinophil activation in patients with post-transplant digestive eosinophilic disorder. These parameters can be used as markers for subsequent development of EGID. PMID:26917244

  15. Steroid responsive eosinophilic gastric outlet obstruction in a child

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gastric outlet obstruction is a rare complication of eosinophilic gastroenteritis, most commonly treated surgically. We report a case of eosinophilic gastric outlet obstruction in a child that responded to conservative medical management. A brief review of this clinical entity is also provided....

  16. Histiocytosis X. Unusual-confusing features of eosinophilic granuloma.

    PubMed

    Pomeranz, S J; Proto, A V

    1986-01-01

    We report our experience with seven cases of eosinophilic granuloma in which unusual and/or confusing features were encountered. These features include: histologic confusion with desquamative interstitial pneumonitis, diffuse histiocytic lymphoma, eosinophilic pneumonia; cysts filled with air and/or fluid; radiographic onset in the eighth decade of life; intratracheal mass; and focal parenchymal consolidation. PMID:3484446

  17. An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock.

    PubMed

    Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P

    2015-01-01

    Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration. PMID:26078733

  18. An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock

    PubMed Central

    Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P.

    2015-01-01

    Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration. PMID:26078733

  19. Mepolizumab for the reduction of exacerbations in severe eosinophilic asthma.

    PubMed

    Russell, Richard; Brightling, Christopher

    2016-06-01

    Asthma affects over 300 million people worldwide and is severe in 10% of sufferers. Severe asthma is associated with greater morbidity and mortality particularly as a consequence of frequent exacerbations. Advances in approaches to phenotype the heterogeneity of severe asthma has established the importance of eosinophilic inflammation and emerging new therapies are broadly designed to target T2-mediated eosinophilic inflammation with the aim to reduce exacerbation frequency. Here, we summarize the evidence that eosinophilic asthma is an important pheno(endo)type and identifies a group at risk of exacerbations; that established therapies reduce exacerbations, particularly in eosinophilic severe asthma; and discuss the role of mepolizumab, an IL-5 neutralising monoclonal antibody therapy, in reducing exacerbations in severe eosinophilic asthma compared to established and other emerging therapies. PMID:27058452

  20. Dermal eosinophilic infiltrate in junctional epidermolysis bullosa.

    PubMed

    Saraiya, Ami; Yang, Catherine S; Kim, Jinah; Bercovitch, Lionel; Robinson-Bostom, Leslie; Telang, Gladys

    2015-08-01

    Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by a split in the lamina lucida usually because of mutations in LAMA3, LAMB3 and LAMC2 resulting in absence or reduction of laminin-332. Rare subtypes of JEB have mutations in COL17A1, ITGB4, ITGA6 and ITGA3 leading to reduction or dysfunction of collagen XVII, integrin α6β4 and integrin α3. The classic finding under light microscopy is a paucicellular, subepidermal split. We describe the unusual presence of an eosinophilic infiltrate in the bullae and subjacent dermis in a neonate with JEB, generalized intermediate (formerly known as non-Herlitz-type JEB), discuss the histologic differential diagnosis for a subepidermal blister in a neonate, review the literature regarding cases of epidermolysis bullosa (EB) presenting with inflammatory infiltrates, and discuss mechanisms to explain these findings. This case highlights that eosinophils can rarely be seen in EB and should not mislead the dermatopathologist into diagnosing an autoimmune blistering disorder. PMID:25950805

  1. Eosinophilic esophagitis: From pathophysiology to treatment

    PubMed Central

    D’Alessandro, Alessandra; Esposito, Dario; Pesce, Marcella; Cuomo, Rosario; De Palma, Giovanni Domenico; Sarnelli, Giovanni

    2015-01-01

    Eosinophilic esophagitis (EoE) is a chronic immune disease, characterized by a dense eosinophilic infiltrate in the esophagus, leading to bolus impaction and reflux-like symptoms. Traditionally considered a pediatric disease, the number of adult patients with EoE is continuously increasing, with a relatively higher incidence in western countries. Dysphagia and food impaction represent the main symptoms complained by patients, but gastroesophageal reflux-like symptoms may also be present. Esophageal biopsies are mandatory for the diagnosis of EoE, though clinical manifestations and proton pump inhibitors responsiveness must be taken into consideration. The higher prevalence of EoE in patients suffering from atopic diseases suggests a common background with allergy, however both the etiology and pathophysiology are not completely understood. Elimination diets are considered the first-line therapy in children, but this approach appears less effective in adults patients, who often require steroids; despite medical treatments, EoE is complicated in some cases by esophageal stricture and stenosis, that require additional endoscopic treatments. This review summarizes the evidence on EoE pathophysiology and illustrates the safety and efficacy of the most recent medical and endoscopic treatments. PMID:26600973

  2. Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis

    PubMed Central

    Masterson, Joanne C; McNamee, Eóin N; Fillon, Sophie A; Hosford, Lindsay; Harris, Rachel; Fernando, Shahan D; Jedlicka, Paul; Iwamoto, Ryo; Jacobsen, Elizabeth; Protheroe, Cheryl; Eltzschig, Holger K; Colgan, Sean P; Arita, Makoto; Lee, James J; Furuta, Glenn T

    2015-01-01

    Objective Eosinophils reside in the colonic mucosa and increase significantly during disease. Although a number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the expanding scope of eosinophil-mediated activities indicate that they also regulate local immune responses and modulate tissue inflammation. We sought to define the impact of eosinophils that respond to acute phases of colitis in mice. Design Acute colitis was induced in mice by administration of dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid or oxazolone to C57BL/6J (control) or eosinophil deficient (PHIL) mice. Eosinophils were also depleted from mice using antibodies against interleukin (IL)-5 or by grafting bone marrow from PHIL mice into control mice. Colon tissues were collected and analysed by immunohistochemistry, flow cytometry and reverse transcription PCR; lipids were analysed by mass spectroscopy. Results Eosinophil-deficient mice developed significantly more severe colitis, and their colon tissues contained a greater number of neutrophils, than controls. This compensatory increase in neutrophils was accompanied by increased levels of the chemokines CXCL1 and CXCL2, which attract neutrophils. Lipidomic analyses of colonic tissue from eosinophil-deficient mice identified a deficiency in the docosahexaenoic acid-derived anti-inflammatory mediator 10, 17- dihydroxydocosahexaenoic acid (diHDoHE), namely protectin D1 (PD1). Administration of an exogenous PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of colitis in eosinophil-deficient mice. The PD1-isomer also attenuated neutrophil infiltration and reduced levels of tumour necrosis factor-α, IL-1β, IL-6 and inducible NO-synthase in colons of mice. Finally, in vitro assays identified a direct inhibitory effect of PD1-isomer on neutrophil transepithelial migration. Conclusions Eosinophils exert a protective effect in acute mouse colitis, via production of anti-inflammatory lipid

  3. Integrin Activation States and Eosinophil Recruitment in Asthma

    PubMed Central

    Johansson, Mats W.; Mosher, Deane F.

    2013-01-01

    Eosinophil arrest and recruitment to the airway in asthma are mediated, at least in part, by integrins. Eosinophils express α4β1, α6β1, αLβ2, αMβ2, αXβ2, αDβ2, and α4β7 integrins, which interact with counter-receptors on other cells or ligands in the extracellular matrix. Whether a given integrin-ligand pair mediates cell adhesion and migration depends on the activation state of the integrin. Integrins exist in an inactive bent, an intermediate-activity extended closed, and a high-activity extended open conformation. Integrin activation states can be monitored by conformation-specific monoclonal antibodies (mAbs). Studies in mice indicate that both β1 and β2 integrins mediate eosinophil recruitment to the lung. In vitro studies indicate that α4β1 and αMβ2 are the principal integrins mediating eosinophil adhesion, including to vascular cell adhesion molecule-1 and the novel αMβ2 ligand periostin. In vivo, blood eosinophils have intermediate-activity β1 integrins, as judged by mAb N29, apparently resulting from eosinophil binding of P-selectin on the surface of activated platelets, and have a proportion of their β2 integrins in the intermediate conformation, as judged by mAb KIM-127, apparently due to exposure to low concentrations of interleukin-5 (IL-5). Airway eosinophils recovered by bronchoalveolar lavage (BAL) after segmental antigen challenge have high-activity β1 integrins and high-activity αMβ2 that does not require IL-5. Here we review information on how the activation states of eosinophil β1 and β2 integrins correlate with measurements of eosinophil recruitment and pulmonary function in asthma. Blood eosinophil N29 reactivity is associated with decreased lung function under various circumstances in non-severe asthma and KIM-127 with BAL eosinophil numbers, indicating that intermediate-activity α4β1 and αMβ2 of blood eosinophils are important for eosinophil arrest and consequently for recruitment and aspects of asthma. PMID

  4. Therapeutic Targeting of Eosinophil Adhesion and Accumulation in Allergic Conjunctivitis

    PubMed Central

    Baiula, Monica; Bedini, Andrea; Carbonari, Gioia; Dattoli, Samantha Deianira; Spampinato, Santi

    2012-01-01

    Considerable evidence indicates that eosinophils are important effectors of ocular allergy. Increased worldwide prevalence of allergic eye pathologies has stimulated the identification of novel drug targets, including eosinophils and adhesion molecules. Accumulation of eosinophils in the eye is a key event in the onset and maintenance of allergic inflammation and is mediated by different adhesion molecules. Antihistamines with multiple mechanisms of action can be effective during the early and late phases of allergic conjunctivitis by blocking the interaction between β1 integrins and vascular cell adhesion molecule (VCAM)-1. Small molecule antagonists that target key elements in the process of eosinophil recruitment have been identified and reinforce the validity of α4β1 integrin as a therapeutic target. Glucocorticoids are among the most effective drugs for ocular allergy, but their use is limited by adverse effects. Novel dissociated glucocorticoids can prevent eosinophil accumulation and induce apoptosis of eosinophils, making them promising candidates for ophthalmic drugs. This article reviews recent understanding of the role of adhesion molecules in eosinophil recruitment in the inflamed conjunctiva along with effective treatments for allergic conjunctivitis. PMID:23271999

  5. Eosinophils In Health and Disease: The LIAR Hypothesis

    PubMed Central

    Lee, James J.; Jacobsen, Elizabeth A.; McGarry, Michael P.; Schleimer, Robert P.; Lee, Nancy A.

    2010-01-01

    Discussions of eosinophils are often descriptions of end-stage effector cells with destructive capabilities mediated predominantly by released cytotoxic cationic granule proteins. Moreover, eosinophils in the medical literature are invariably associated with the pathologies linked with helminth infections or allergic diseases such as asthma. This has led to an almost fatalist view of eosinophil effector functions and associated therapeutic strategies targeting these cells that would make even William of Ockham proud - eosinophil effector functions have physiological consequences that increase patient morbidity/mortality and “the only good eosinophils are dead eosinophils”. Unfortunately, the strengths of dogmas are also their greatest weaknesses. Namely, while the repetitive proclamation of dogmatic concepts by authoritative sources (i.e., reviews, meeting proceedings, textbooks, etc.) builds consensus within the medical community and lower the entropies surrounding difficult issues, they often ignore not easily explained details and place diminished importance on alternative hypotheses. The goal of this perspective is two fold: (i) We will review recent observations regarding eosinophils and their activities as well as reinterpret earlier data as part of the synthesis of a new paradigm. In this paradigm, we hypothesize that eosinophils accumulate at unique sites in response to cell turnover or in response to local stem cell activity(ies). We further suggest that this accumulation is part of one or more mechanisms regulating tissue homeostasis. Specifically, instead of immune cells exclusively mediating innate host defense, we suggest that accumulating tissue eosinophils are actually regulators of Local Immunity And/or Remodeling/Repair in both health and disease - The LIAR Hypothesis; (ii) We want to be inflammatory (pun intended!) and challenge the currently common perspective of eosinophils as destructive end-stage effector cells. Our hope is to create more

  6. Nasal Eosinophilic Angiocentric Fibrosis with Orbital Extension.

    PubMed

    Faramarzi, Mohammad; Dadgarnia, Mohammad Hossein; Moghimi, Mansour; Sharouny, Hadi; Behniafard, Nasim

    2015-09-01

    Eosinophilic angiocentric fibrosis (EAF) is an extremely rare, chronic, benign, idiopathic disorder that mostly affects the upper respiratory tract, particularly the nasal cavity, and features progressive submucosal perivascular fibrosis. To the best of our knowledge, only seven cases of EAF with orbital involvement have been reported. We report a case of sinonasal EAF with orbital extension that presented with left nasolacrimal duct obstruction. A 35-year-old man presented with left epiphora, proptosis, anterolateral globe displacement and nasal obstruction. Endoscopic sinus examination showed a firm, gritty, creamy, yellow, fibrous, adherent mass of maxillary sinus. Diagnosis was established with histopathological examination of excisional biopsy of the lesion. Although EAF is very rare, it should be considered in the differential diagnosis of lesions of upper airway tract, particularly the nasal cavity. Biopsy is necessary for diagnosis and treatment planning. Resecting of the involved tissues completely is essential for prevention of recurrence. PMID:25601283

  7. Spontaneous resolution of lumbar vertebral eosinophilic granuloma.

    PubMed

    Bavbek, M; Atalay, B; Altinörs, N; Caner, H

    2004-02-01

    Eosinophilic granuloma (EG) is a rare disease but is more common in adults than children. It's often self-limiting. Spinal involvement is rare. It is the localized and most benign form of Langerhans' cell histiocytosis (previously known as histiocytosis X), characterised by lytic lesions in one or more bones. Spontaneous resolution of vertebral body lesions is very rare. In this case, the patient had one EG in a cervical vertebra and a similar lesion in a lumbar vertebra. This case is important because it featured a symptomatic lesion in the cervical spine accompanied by an asymptomatic lesion in a lumbar vertebra. We treated the cervical lesion by surgical fusion and followed the lumbar lesion up conservatively, with the patient in a corset. After 8 years of follow-up, control MRI showed that the lumbar lesion had spontaneously resolved. PMID:14963750

  8. Major neutrophil functions subverted by Porphyromonas gingivalis

    PubMed Central

    Olsen, Ingar; Hajishengallis, George

    2016-01-01

    Polymorphonuclear leukocytes (neutrophils) constitute an integrated component of the innate host defense in the gingival sulcus/periodontal pocket. However, the keystone periodontal pathogen Porphyromonas gingivalis has in the course of evolution developed a number of capacities to subvert this defense to its own advantage. The present review describes the major mechanisms that P. gingivalis uses to subvert neutrophil homeostasis, such as impaired recruitment and chemotaxis, resistance to granule-derived antimicrobial agents and to the oxidative burst, inhibition of phagocytic killing while promoting a nutritionally favorable inflammatory response, and delay of neutrophil apoptosis. Studies in animal models have shown that at least some of these mechanisms promote the dysbiotic transformation of the periodontal polymicrobial community, thereby leading to inflammation and bone loss. It is apparent that neutrophil–P. gingivalis interactions and subversion of innate immunity are key contributing factors to the pathogenesis of periodontal disease. PMID:26993626

  9. An Overview of the Diagnosis and Management of Eosinophilic Esophagitis

    PubMed Central

    Singla, Manish B; Moawad, Fouad J

    2016-01-01

    Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by symptoms of esophageal dysfunction and eosinophilic infiltration of the esophageal mucosa. The diagnosis requires esophageal biopsies demonstrating at least 15 eosinophils per high-powered field following a course of high-dose proton pump inhibitors. Management of EoE consists of the three Ds: drugs, dietary therapy, and esophageal dilation. In this review, we discuss the epidemiology, pathogenesis, diagnosis, and treatment of EoE to include the role of emerging therapies. PMID:26986655

  10. A case of feline gastrointestinal eosinophilic sclerosing fibroplasia.

    PubMed

    Suzuki, Manabu; Onchi, Miyako; Ozaki, Masakazu

    2013-03-01

    Feline gastrointestinal eosinophilic sclerosing fibroplasia was diagnosed in an 8-month-old Scottish fold that had a primary gastrointestinal mass involving the stomach, duodenum and mesenteric lymph nodes. Histopathologically, the most characteristic feature of this mass was granulation tissue with eosinophil infiltration and hyperplasia of sclerosing collagen fiber. Immunohistochemically, large spindle-shaped cells were positive for smooth muscle actin and vimentin. This case emphasizes the importance of feline gastrointestinal eosinophilic sclerosing fibroplasia as a differential diagnosis of gastrointestinal neoplastic lesions such as osteosarcoma and mast cell tumor in cats. PMID:23723568

  11. Biologic Therapies Targeting Eosinophils: Current Status and Future Prospects

    PubMed Central

    Legrand, Fanny; Klion, Amy

    2015-01-01

    The recent explosion in the number of biologic therapies in clinical development for the treatment of eosinophilic disorders is unprecedented. As these agents become available for clinical use, the selection of the most appropriate agent for a given patient will become increasingly complicated. The aims of this review are twofold: 1) to present the lessons learned from clinical trials using the first generation of eosinophil-targeted biologics (anti-IL-5 antibodies), and 2) to discuss the advantages and potential limitations of currently available and novel targeted therapies to treat eosinophilic disorders. PMID:25754717

  12. Chronic Eosinophilic Leukemia Presenting Predominantly with Cutaneous Manifestations

    PubMed Central

    Vidyadharan, Suja; Joseph, Bebisha; Nair, Sukumaran Pradeep

    2016-01-01

    A 37-year-old male presented with severe oral and genital mucosal ulcers, lichenoid eruption and twenty-nail dystrophy. Systemic examination was normal, except for anemia. On investigations, he was found to have persistently elevated peripheral eosinophilia, absolute eosinophil count >5000/mm3, bone marrow showing increased eosinophilic precursors, and infiltration by atypical cells. The serum vitamin B12 levels were grossly elevated, and Philadelphia chromosome study was negative. Thus, a diagnosis of chronic eosinophilic leukemia was made. The patient showed excellent response to imatinib mesylate. We are reporting a rare type of leukemia presenting with predominantly cutaneous manifestations. PMID:27512192

  13. Development of Eosinophilic Fasciitis during Infliximab Therapy for Psoriatic Arthritis

    PubMed Central

    Hariman, Richard; Patel, Payal; Strouse, Jennifer; Collins, Michael P.; Rosenthal, Ann

    2016-01-01

    Eosinophilic fasciitis (EF) is a rare disorder involving chronic inflammation of the fascia and connective tissue surrounding muscles, nerves, and blood vessels. While its pathogenesis is not entirely understood, this disorder is thought to be autoimmune or allergic in nature. We present here a case of a 59-year-old male who developed peripheral eosinophilia and subsequent eosinophilic fasciitis during treatment with infliximab. To our knowledge, eosinophilic fasciitis has not been previously described in patients during treatment with an inhibitor of tumor necrosis factor α. PMID:27293946

  14. Chronic Eosinophilic Leukemia Presenting Predominantly with Cutaneous Manifestations.

    PubMed

    Vidyadharan, Suja; Joseph, Bebisha; Nair, Sukumaran Pradeep

    2016-01-01

    A 37-year-old male presented with severe oral and genital mucosal ulcers, lichenoid eruption and twenty-nail dystrophy. Systemic examination was normal, except for anemia. On investigations, he was found to have persistently elevated peripheral eosinophilia, absolute eosinophil count >5000/mm(3), bone marrow showing increased eosinophilic precursors, and infiltration by atypical cells. The serum vitamin B12 levels were grossly elevated, and Philadelphia chromosome study was negative. Thus, a diagnosis of chronic eosinophilic leukemia was made. The patient showed excellent response to imatinib mesylate. We are reporting a rare type of leukemia presenting with predominantly cutaneous manifestations. PMID:27512192

  15. Disseminated eosinophilic disease resembling idiopathic hypereosinophilic syndrome in a dog.

    PubMed

    Aroch, I; Perl, S; Markovics, A

    2001-09-29

    True idiopathic hypereosinophilic syndrome has been described in human beings and cats, but not in dogs. The syndrome is characterised by prolonged unexplained peripheral mature eosinophilia, the infiltration of many organs by eosinophils, organ dysfunction and a fatal outcome. This paper describes an idiopathic disseminated eosinophilic disease in a dog involving various organs, manly the heart and the lungs, accompanied by a leukemoid eosinophilic response, and a fatal outcome. The histopathological findings included the infiltration of the myocardium, lung parenchyma, liver, spleen, lymph nodes and skeletal muscles with eosiniphils. PMID:11601516

  16. Immunohistochemical detection of deposits of eosinophil-derived neurotoxin and eosinophil peroxidase in the myocardium of patients with Chagas' disease.

    PubMed Central

    Molina, H A; Kierszenbaum, F

    1988-01-01

    An immunohistochemical study of eosinophil distribution in the inflammatory cell infiltrates of four different types of myocardial lesions associated with Chagas' disease--caused by Trypanosoma cruzi--showed larger numbers of these cells in areas presenting tissue necrosis and degeneration, most notably in patients with the most severe myocarditis from a histopathological stand-point. Using antisera specific for human eosinophil-derived neurotoxin or eosinophil peroxidase, we detected deposits of these secretion products on myofibres and in the interstitium of chagasic myocardium displaying necrosis and degeneration but rarely in other types of lesions. These deposits were not detectable in the myocardium of non-chagasic patients who had died from myocardial infarction (acute or in the scarring stage) or myocarditis secondary to bacterial endocarditis. When human eosinophil-derived neurotoxin was incubated with myoblast monolayers there was a significant cell injury, detachment and lysis. These effects were abrogated by yeast RNA, added as a competitive ribonuclease substrate, and inhibited by the ribonuclease inhibitor RNasin, suggesting that the ribonuclease activity of the eosinophil-derived neurotoxin was involved in the effect. These results suggest a link between eosinophil infiltration and necrosis in chagasic myocardial lesions and point to EDN, and perhaps other toxic eosinophil secretion products, as possible mediators of tissue damage. Images Figure 1 Figure 2 PMID:3049321

  17. EGYPTIAN EOSINOPHILIC AND INFECTIOUS MENINGOENCEPHA- LITIS AND THEIR IMPACT ON PSYCHOLOGICAL ASPECTS.

    PubMed

    El-Bahnasawy, Mamdouh M M; El Feky, Mohammad Reda; Morsy, Ayman T A; Ismail, Mousa A M; Morsy, Tosson A

    2016-04-01

    Meningoencephalitis is an acute inflammation of the brain and spinal cord & their covering protective membranes. Meningitis can be life-threatening because of the inflammation's proximity to the brain and spinal cord; therefore, the condition is classified as a medical emergency. The commonest symptoms of meningitis are headache and neck stiffness associated with fever, confusion or altered consciousness, vomiting, and an inability to tolerate light (photophobia) or loud noises (phonophobia). Children often exhibit only nonspecific symptoms, such as irritability and drowsiness. If a rash is present, it may indicate a particular cause of meningitis; for instance, meningitis caused by meningococcal bacteria may be accompanied by a characteristic rash. A broad variety of allergic, infectious, neoplastic, and idiopathic diseases are associated with increased blood and/or tissue eosinophilia and range in severity from self-limited conditions to life-threatening disorders. Although accepted upper limits of normal blood eosinophil numbers vary somewhat, a value above 600 eosinophils /microL of blood is abnormal in the vast majority of cases. Generally speaking, there are several possible causes of eosinophils in the CSF; undoubtedly parasitic infection is one of the main causes. PMID:27363042

  18. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma.

    PubMed

    Pelaia, Girolamo; Vatrella, Alessandro; Busceti, Maria Teresa; Gallelli, Luca; Calabrese, Cecilia; Terracciano, Rosa; Maselli, Rosario

    2015-01-01

    Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments. PMID:25878402

  19. Eosinophilic gastroenteritis: a challenge to diagnose and treat.

    PubMed

    Phaw, Naw April; Tsai, Her Hsin

    2016-01-01

    The patient presented with bloody diarrhoea, and crampy abdominal pains. She was diagnosed with eosinophilic gastroenteritis (EGE) after the finding of persistently high peripheral eosinophil counts and histology of endoscopic biopsies. She responded to steroids but became dependent on it and her symptoms recurred on steroid tapering. There was little improvement with alternative treatment such as budesonides, azathioprine and montelukast. Surprisingly her symptoms improved significantly after she was treated with clarithromycin for chest infection and she was continued on clarithromycin. Her eosinophil counts fell dramatically and follow-up CT (thorax, abdomen and pelvic) scan showed the mucosal thickening had improved. She became completely free of the symptoms since she was on clarithromycin and her eosinophils counts fell within the normal range during the follow-up. PMID:27613263

  20. Diagnosis and management of eosinophilic asthma: a US perspective

    PubMed Central

    Walford, Hannah H; Doherty, Taylor A

    2014-01-01

    Eosinophilic asthma is now recognized as an important subphenotype of asthma based on the pattern of inflammatory cellular infiltrate in the airway. Eosinophilic asthma can be associated with increased asthma severity, atopy, late-onset disease, and steroid refractoriness. Induced sputum cell count is the gold standard for identifying eosinophilic inflammation in asthma although several noninvasive biomarkers, including fractional exhaled nitric oxide and periostin, are emerging as potential surrogates. As novel therapies and biologic agents become increasingly available, there is an increased need for specific phenotype-directed treatment strategies. Greater recognition and understanding of the unique immunopathology of this asthma phenotype has important implications for management of the disease and the potential to improve patient outcomes. The present review provides a summary of the clinical features, pathogenesis, diagnosis, and management of eosinophilic asthma. PMID:24748808

  1. Recurrent Postpartum Eosinophilic Pneumonia Presenting as Acute Respiratory Distress Syndrome

    PubMed Central

    Ucar, Elif Yilmazel; Araz, Omer; Yilmaz, Nafiye; Akgun, Metin

    2011-01-01

    Eosinophilic pneumonia (EP) is a rare disease of the lung. We aimed to present atypical course of two EP cases. They were admitted to our hospital because of acute respiratory distress syndrome (ARDS) in postpartum period. Eosinophilia was detected in bronchoscopic bronchoalveolar lavage and laboratory examination. In these cases, no spesific cause for eosinophilic pneumonia was determined and steroid treatment was started. After the treatment, the patients were in full recovery which were confirmed by clinical and radiological investigations, readmitted to our clinic with relapses of ARDS. The patients have received regular treatment for 1 year. Our cases were neither fitting the classic definitions of acute eosinophilic pneumonia nor chronic eosinophilic pneumonia. Therefore, we wanted to contribute additional data in the literature by sharing these interesting cases. PMID:25610194

  2. Cellular Mechanisms Underlying Eosinophilic and Neutrophilic Airway Inflammation in Asthma

    PubMed Central

    Vatrella, Alessandro; Busceti, Maria Teresa; Gallelli, Luca; Calabrese, Cecilia; Terracciano, Rosa

    2015-01-01

    Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments. PMID:25878402

  3. UNUSUAL EOSINOPHILIC GRANULE CELL PROLIFERATION IN COHO SALMON (ONCHORHYNCHUS KISUTCH)

    EPA Science Inventory

    Proliferative lesions comprised of eosinophilic granule cells (EGCs) extended throughout the gastrointestinal tract of several mature, spawning coho salmon Oncorhynchus kisutch (Walbaum). istological examination of the tumour showed extensive proliferation and infiltration of EGC...

  4. Eosinophilic Gastroenteritis as a Rare Cause of Recurrent Epigastric Pain

    PubMed Central

    Safari, Mohammad Taghi; Shahrokh, Shabnam; Miri, Mohammad Bagher; Ehsani Ardakani, Mohammad Javad

    2016-01-01

    Eosinophilic gastroenteritis (EGE) is a rare inflammatory disorder of gastrointestinal tract characterized by eosinophilic infiltration of the bowel wall. It can mimic many gastrointestinal disorders due to its wide spectrum of presentations. Diagnose is mostly based on excluding other disorders and a high suspicion. Here we report a case of 26 year old man with a history of sever epigastric pain followed by nausea, vomiting since a few days before admission with final diagnosis of EGE.

  5. Co-existent eosinophilic gastroenteritis and hypothalamic-pituitary dysfunction.

    PubMed Central

    Haeney, M. R.; Wilson, R. J.

    1977-01-01

    A case of eosinophilic gastroenteritis in a 42-year-old man is described. The patient had diarrhoea, faecal blood loss, a protein-losing enteropathy, malabsorption of fat, xylose and vitamin B12. Co-existent hypopituitarism, diabetes insipidus and hypothalamic dysfunction was demonstrated. Complete clinical recovery occurred with pituitary replacement therapy alone. The association of this endocrine abnormality with the picture of eosinophilic gastroenteritis has not previously been described. Images Fig. 1 PMID:882484

  6. [MORPHOLOGICAL FEATURES OF NEUTROPHILS AND EOSINOPHILS GRANULES IN SAPPHIRE MINKS].

    PubMed

    Uzenbaeva, L B; Kizhina, A G; Ilyukha, V A

    2015-01-01

    It has been established that sapphire minks have abnormality of subcellular structure of blood and bone marrow neutrophils and eosinophils. The abnormality consists in forming of abnormal "giant" granules. The si- ze and the number of abnormal granules significantly change during maturation of leucocytes in bone marrow. We have found differences between abnormal granules forming in neutrophils and eosinophils that depend on the maturing stage and the cells life cycle duration as well as morphofunctional features of these granulocytes. PMID:26863773

  7. Toward the Proteome of the Human Peripheral Blood Eosinophil

    PubMed Central

    Straub, Christof; Pazdrak, Konrad; Young, Travis W.; Stafford, Susan J.; Wu, Zheng; Wiktorowicz, John E.; Haag, Anthony M.; English, Robert D.; Soman, Kizhake V.; Kurosky, Alexander

    2010-01-01

    Eosinophils are granular leukocytes that have significant roles in many inflammatory and immunoregulatory responses, especially asthma and allergic diseases. We have undertaken a fairly comprehensive proteomic analysis of purified peripheral blood eosinophils from normal human donors primarily employing 2-dimensional gel electrophoresis with protein spot identification by matrix-assisted laser desorption/ionization mass spectrometry. Protein subfractionation methods employed included isoelectric focusing (Zoom® Fractionator) and subcellular fractionation using differential protein solubilization. We have identified 3,141 proteins which had Mascot expectation scores of 10−3 or less. Of these 426 were unique and non-redundant of which 231 were novel proteins not previously reported to occur in eosinophils. Ingenuity Pathway Analysis showed that some 70% of the non-redundant proteins could be subdivided into categories that are clearly related to currently known eosinophil biological activities. Cytoskeletal and associated proteins predominated among the proteins identified. Extensive protein posttranslational modifications were evident, many of which have not been previously reported that reflected the dynamic character of the eosinophil. This dataset of eosinophilic proteins will prove valuable in comparative studies of disease versus normal states and for studies of gender differences and polymorphic variation among individuals. PMID:21048890

  8. Elimination and elemental diet therapy in eosinophilic oesophagitis.

    PubMed

    Warners, M J; Vlieg-Boerstra, B J; Bredenoord, A J

    2015-10-01

    Eosinophilic oesophagitis (EoE) is a chronic immune-mediated disorder of the oesophagus. The incidence of EoE has been raised substantially and EoE has recently become the most prevalent cause of dysphagia among the adolescents. Food and aeroallergens are believed to play a major role in the pathogenesis. Current treatment includes topical steroids and dietary therapy. Dietary therapy with elimination of causative allergens could provide a durable long-term solution. Dietary therapy in EoE consists of in elemental and empiric elimination diets. Elemental diet with amino acid-based formula is most effective in achieving disease remission but poor taste makes adherence challenging. Empiric elimination diet based on avoidance of most common food allergens offers moderate response rates, the usefulness of allergy test-directed elimination diets is questioned by low response rates. In conclusion, dietary treatments for EoE seem promising, but further refinement is required before it can become standard care. PMID:26552778

  9. Clara cells drive eosinophil accumulation in allergic asthma.

    PubMed

    Sonar, S S; Ehmke, M; Marsh, L M; Dietze, J; Dudda, J C; Conrad, M L; Renz, H; Nockher, W A

    2012-02-01

    Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the "immunomodulatory barrier" of the airway epithelium. To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 μg endotoxin-free ovalbumin in conjunction with naphthalene-induced Clara cell depletion. Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung. These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma. PMID:21828027

  10. Clinical features of Eosinophilic esophagitis in children and adults.

    PubMed

    Miehlke, Stephan

    2015-10-01

    Eosinophilic esophagitis (EoE) may affect humans at any age with a predominance for Caucasian males. The clinical manifestation of EoE varies depending on the patient's age. Infants and young children may primarily present with unspecific symptoms such as feeding problems, vomiting and abdominal pain. In adolescents and adults, dysphagia and food impactation become the predominant symptoms. EoE should also be considered in cases of refractory heartburn in both children and adults. Concomitant allergic diseases such as asthma, rhinitis and eczema, as well as peripheral eosinophilia and elevated total serum IgE values are common in pediatric and adult EoE patients. EoE seems to be primarily a food antigen-driven disease, whereas in adults, aeroallergen sensitization may dominate. Endoscopic features of EoE include mucosal edema, furrows, exudates, corrugated rings, strictures, and the so-called crepe paper sign. There appears to be a shift from an inflammatory-predominant phenotype in young childhood towards a more fibrotic phenotype in adolescents and adults. Long-term follow studies suggest that EoE is a chronic and potentially progressive disease causing recurring dysphagia in the majority of cases. The prevalence of strictures significantly increases with the duration of untreated disease, stressing the importance of early diagnosis and consequent treatment of EoE. PMID:26552773

  11. Eosinophil hematopoietins antagonize the programmed cell death of eosinophils. Cytokine and glucocorticoid effects on eosinophils maintained by endothelial cell-conditioned medium.

    PubMed Central

    Her, E; Frazer, J; Austen, K F; Owen, W F

    1991-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) was established as the constitutive and elicited human umbilical vein endothelial cell-derived eosinophil viability-sustaining factor. Stimulation of endothelium cell monolayers with IL-1 alpha (5 U/ml) increased the 48-h elaboration of GM-CSF from a mean of 3.2 to a mean of 8.2 pM (P less than 0.05). Dexamethasone (100 nM) decreased the constitutive GM-CSF elaboration by 49% (P less than 0.001) but did not diminish production by IL-1 alpha-stimulated endothelium. However, eosinophil viability decreased by 21% in dexamethasone-pretreated IL-1 alpha-stimulated endothelial cell-conditioned medium (P less than 0.05), which suggested viability antagonism by glucocorticoids. After 24 h of culture, eosinophil viability for replicate cells in enriched medium alone or with 1 pM GM-CSF decreased from means of 43 and 75% to means of 21 and 54%, respectively, when dexamethasone was included (P less than 0.05). However, 10 pM GM-CSF, IL-3, or IL-5 protected the cells against dexamethasone and against endonuclease-specific DNA fragmentation. In this model system of eosinophil-tissue interactions, dexamethasone prevents the endothelial cells from inducing a pathobiologic phenotypic change in the eosinophil by suppression of GM-CSF elaboration to concentrations that are not cytoprotective. Cytokine priming by GM-CSF, IL-3, or IL-5 may account for the differential responsiveness of select eosinophilic disorders to glucocorticoids. Images PMID:1752957

  12. Redox thermodynamics of lactoperoxidase and eosinophil peroxidase.

    PubMed

    Battistuzzi, Gianantonio; Bellei, Marzia; Vlasits, Jutta; Banerjee, Srijib; Furtmüller, Paul G; Sola, Marco; Obinger, Christian

    2010-02-01

    Eosinophil peroxidase (EPO) and lactoperoxidase (LPO) are important constituents of the innate immune system of mammals. These heme enzymes belong to the peroxidase-cyclooxygenase superfamily and catalyze the oxidation of thiocyanate, bromide and nitrite to hypothiocyanate, hypobromous acid and nitrogen dioxide that are toxic for invading pathogens. In order to gain a better understanding of the observed differences in substrate specificity and oxidation capacity in relation to heme and protein structure, a comprehensive spectro-electrochemical investigation was performed. The reduction potential (E degrees ') of the Fe(III)/Fe(II) couple of EPO and LPO was determined to be -126mV and -176mV, respectively (25 degrees C, pH 7.0). Variable temperature experiments show that EPO and LPO feature different reduction thermodynamics. In particular, reduction of ferric EPO is enthalpically and entropically disfavored, whereas in LPO the entropic term, which selectively stabilizes the oxidized form, prevails on the enthalpic term that favors reduction of Fe(III). The data are discussed with respect to the architecture of the heme cavity and the substrate channel. Comparison with published data for myeloperoxidase demonstrates the effect of heme to protein linkages and heme distortion on the redox chemistry of mammalian peroxidases and in consequence on the enzymatic properties of these physiologically important oxidoreductases. PMID:19944669

  13. Management of Eosinophilic Esophagitis During Pregnancy.

    PubMed

    Burk, Caitlin M; Long, Millie D; Dellon, Evan S

    2016-07-01

    There are currently limited data on the management of eosinophilic esophagitis (EoE) during pregnancy. At our center, however, we have followed several pregnant women with EoE and others have asked pertinent questions in pre-pregnancy counseling. The relatively young age of patients with EoE implies that many practitioners will also encounter patients with these questions. In this review, we use four cases to prompt a discussion about concerns focused on the safety of steroids and diet therapy during pregnancy and breast-feeding, potential nutritional risks with dietary elimination, how to optimize therapy, and whether endoscopic evaluation for monitoring of disease activity is safe during pregnancy and breast-feeding. An additional concern is whether the disease could progress during pregnancy and breast-feeding if no therapies are used. Although there are no studies specifically examining pregnant EoE patients, we have reviewed the literature relevant to this population as informed by the treatment of inflammatory bowel disease patients during pregnancy, where these issues have been studied in more depth. Providers who care for EoE patients who could become pregnant should familiarize themselves with these issues. PMID:26888769

  14. Diagnosis and classification of eosinophilic fasciitis.

    PubMed

    Pinal-Fernandez, I; Selva-O' Callaghan, A; Grau, J M

    2014-01-01

    Eosinophilic fasciitis (EF) is a rare scleroderma-like syndrome with an unknown etiology and pathogenesis that should be considered an immune-allergic disorder. Painful swelling with progressive induration and thickening of the skin and soft tissues of the limbs and trunk are the clinical hallmarks of the disease. Peripheral blood eosinophilia, hypergammaglobulinemia, and elevated erythrocyte sedimentation rate are the main laboratory findings. Full-thickness wedge biopsy of the clinically affected skin showing inflammation and thickening of deep fascia is essential to establish the diagnosis. The differential diagnosis includes systemic sclerosis and other scleroderma subsets such as morphea, and epidemic fasciitis syndromes caused by toxic agents such as the myalgia-eosinophilia syndrome and toxic oil syndrome. Peripheral T cell lymphomas should also be ruled out. The diagnosis of EF can be established by clinical, laboratory and histological findings, but universally accepted international diagnostic criteria are lacking. Corticosteroids are efficacious and remain the standard therapy for EF, although some patients may improve spontaneously. PMID:24424187

  15. Eosinophilic Fasciitis Associated with Mycoplasma arginini Infection

    PubMed Central

    Silló, Pálma; Pintér, Dóra; Ostorházi, Eszter; Mazán, Mercedes; Wikonkál, Norbert; Pónyai, Katinka; Volokhov, Dmitriy V.; Chizhikov, Vladimir E.; Szathmary, Susan; Stipkovits, Laszlo

    2012-01-01

    Eosinophilic fasciitis (EF) with generalized sclerodermiform skin lesions developed over a 19-month period in a previously healthy 23-year-old man. Although we confirmed EF by skin histology and laboratory tests, the recurrent fevers and the clinical observation of sclerotic prepuce with urethritis indicated further bacteriological analysis by conventional microbiological and DNA-based tests. Urethra cultures were positive for an arginine-hydrolyzing mycoplasma and Ureaplasma urealyticum. The patient also had serum IgM antibodies to Mycoplasma pneumoniae using enzyme-linked immunosorbent assay (ELISA)-based qualitative detection. Mycoplasma arginini was isolated from two independent venous blood serum samples and was identified by conventional microbiological tests and sequencing of the 16S rRNA and rpoB genes (GenBank sequence accession numbers HM179555 and HM179556, respectively). M. arginini genomic DNA also was detected by species-specific PCR in the skin lesion biopsy sample. Treatment with corticosteroids and long-term courses of selected antibiotics led to remission of skin symptoms and normalization of laboratory values. This report provides the first evidence of EF associated with mycoplasma infection and the second report of human infection with M. arginini and therefore suggests that this mycoplasma infection might have contributed to the pathogenesis of the disease. PMID:22189109

  16. Eosinophilic Esophagitis: An Evidence-Based Approach to Therapy.

    PubMed

    González-Cervera, J; Lucendo, A J

    2016-01-01

    In recent years, several randomized controlled trials and meta-analyses have evaluated the efficacy of the various therapeutic options available for treating patients with eosinophilic esophagitis, including dietary modifications, proton pump inhibitors, topical corticosteroids, and endoscopic esophageal dilation. Proton pump inhibitors are currently considered the first-line treatment for eosinophilic esophagitis, achieving histological remission and improvement of symptoms in 50.5% and 60.8% of patients, respectively. The efficacy of topical corticosteroids in eosinophilic esophagitis has been assessed in several trials. Meta-analyses summarizing results indicate that budesonide and fluticasone propionate are significantly superior to placebo, both in decreasing eosinophil densities in the esophageal mucosa and in relieving symptoms. However, owing to differences in drug delivery, viscous budesonide seems to be the best pharmacological therapy for eosinophilic esophagitis. Results for dietary modifications have been mixed depending on the type of diet prescribed. Thus, while exclusive amino acid-based elemental diets are the most effective in inducing histological remission of eosinophilic esophagitis (90.8%), their severe drawbacks limit their implementation in clinical practice. Allergy testing-based food elimination provides a suboptimal remission rate of 45.5%, although this is lower in adults than in children (32.2% vs 47.9%, respectively). In addition, the various available studies are highly heterogeneous. Empirical 6-food elimination diets were shown to be the best diet-based therapy, with a homogeneous remission rate of 72%. Simpler, more convenient empirical schemes have also been evaluated. The aim of this review is to provide an evidence-based overview on the efficacy of the options available for treatment of eosinophilic esophagitis along with a practical management algorithm. PMID:27012011

  17. Eosinophilic gastroenteritis associated with eosinophilic cystitis: Computed tomography and magnetic resonance imaging findings.

    PubMed

    Han, Shu-Gao; Chen, Ying; Qian, Zi-Hua; Yang, Li; Yu, Ri-Sheng; Zhu, Xiu-Liang; Li, Qing-Hai; Chen, Qian

    2015-03-14

    Eosinophilic gastroenteritis (EG) is a rare, distinct clinical entity, and EG associated with eosinophilic cystitis (EC) is extremely rare and has not been well documented. Here, we report two cases of EG and coexistent EC along with findings from computed tomography (CT) and magnetic resonance imaging (MRI). An 18-year-old male with a history of hematuria, urgency and occasional urodynia for two weeks and a 34-year-old male with a history of abdominal distention for one week were admitted to our hospital. Abdominal contrast-enhanced CT in both patients revealed wall thickening in different parts of the gastrointestinal tract with inhomogeneous reinforcement, coexistent with local or diffuse bladder wall thickening with progressive enhancement, and also showed that the bladder mucosal lining was nondestructive. Pelvic MRI showed that the local or diffuse thickened bladder wall was iso-intense on T1-weighted images, hypo-intense on T2-weighted images, and slightly restricted on diffusion weighted imaging (DWI) in one case. After therapy, the thickened wall of the gastrointestinal tract and urinary bladder had improved markedly in the two cases. To the best of our knowledge, this is the first report on the radiological imaging of EG and coexistent EC by both CT and MRI and the first with DWI findings. PMID:25780317

  18. Nitric oxide regulates human eosinophil adhesion mechanisms in vitro by changing integrin expression and activity on the eosinophil cell surface

    PubMed Central

    Conran, N; Ferreira, H H A; Lorand-Metze, I; Thomazzi, S M; Antunes, E; de Nucci, G

    2001-01-01

    The nitric oxide synthase (NOS) inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), inhibits both rat and human eosinophil chemotaxis in vitro. Here, the role of nitric oxide (NO) in human eosinophil cell surface integrin expression and function was investigated. Human peripheral blood eosinophils were treated with L-NAME (0.01 – 1.0 mM) and their adhesion to human fibronectin and serum observed. Adhesion of cells to fibronectin and serum increased by 24.0±4.6 and 43.8±4.7%, respectively, when eosinophils were treated with 1.0 mM L-NAME. Increased adhesion by L-NAME could be abolished when cells were co-incubated with VLA-4- and Mac-1-specific monoclonal antibodies (mAbs). The NO donor, sodium nitroprusside (2.5 mM), significantly inhibited eosinophil adhesion to fibronectin and serum by 34.3±4.5 and 45.2±5.6%, respectively. This inhibition was accompanied by a 4 fold increase in the levels of intracellular cyclic GMP. Flow cytometrical analysis demonstrated that L-NAME induced an increased expression of CD11b (Mac-1) on the eosinophil cell surface of 36.3±7.4%. L-NAME had no effect upon CD49d (VLA-4) expression. Treatment of human eosinophils, in vitro, with H-[1,2,4] oxadiazolo quinoxalin-1-one (ODQ) (0.1 mM), an inhibitor of soluble guanylate cyclase, also significantly increased eosinophil adhesion to fibronectin and serum by 73.5±17.9 and 91.7±12.9%, respectively. This increase in adhesion could also be inhibited by co-incubation with the Mac-1 and VLA-4-specific mAbs. In conclusion, results indicate that NO, via a cyclic GMP-dependent mechanism, inhibits the adhesion of human eosinophils to the extracellular matrix (ECM). This inhibition is accompanied by a decrease in the expression and function of the eosinophil's adhesion molecules, in particular, the expression of the Mac-1 integrin and the function of the VLA-4 integrin. PMID:11588118

  19. Modulation of human eosinophil polymorphonuclear leukocyte migration and function.

    PubMed Central

    Goetzl, E. J.

    1976-01-01

    Eosinophil migration toward a concentration gradient of a chemotactic factor is regulated at four levels. Diverse immunologic pathways generate stimuli with eosinophil chemotactic activity, including the complement products C5a and a fragment of C3a and the peptide products of mast cells and basophils activated by IgE-mediated reactions, such as eosinophil chemotactic factor of anaphylaxis (ECF-A) and other oligopeptides. The intrinsic preferential leukocyte activity of the chemotactic stimuli represents the second level of modulation, with ECF-A and other mast cell-derived peptides exhibiting the most selective action on eosinophils. The third level of control of eosinophil chemotaxis is composed of inactivators and inhibitors of chemotactic stimuli and is exemplified by degradation of C5a by anaphylatoxin inactivator or chemotactic factor inactivator and of ECF-A by carboxypeptidase-A or aminopeptidases. The activity of ECF-A is uniquely suppressed by equimolar quantities of its NH2- terminal tripeptide substituent, presumably by eosinophil membrane receptor competition. Factors comprising the fourth level of regulation, which alter eosinophil responsiveness to chemotactic stimuli, include the chemotactic factors themselves, through deactivation; nonchemotactic inhibitors such as the COOH-terminal tripeptide substituent of ECF-A, the neutrophil-immobilizing factor (NIF), the phagocytosis-enhancing factor Thr-Lys-Pro-Arg, and histamine at concentrations greater than 400 ng/ml; and nonchemotactic enhancing principles represented by ascorbate and by histamine at concentrations of 30 ng/ml or less. Local concentrations of eosinophils called to and immobilized at the site of a hypersenitivity reaction may express their regulatory functions by degrading the chemical mediators elaborated including histamine, slow-reacting substance of anaphylaxis (SRS-A), and platelet-activating factor (PAF) by way of their content of histaminase, arylsulfatase B, and phospholipase D

  20. Advances in Clinical Management of Eosinophilic Esophagitis

    PubMed Central

    Dellon, Evan S.; Liacouras, Chris A.

    2014-01-01

    EoE is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsies, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE). We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histologic features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and PPI-REE. It is also important to consider the epidemiology of EoE (current incidence of 1/10,000 new cases per year and prevalence of 0.5-1/1,000 cases per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and non-directed empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenostic complications of EoE. There are number of unresolved issues in EoE, including phenotypes, optimal treatment endpoints, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines—EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians. PMID:25109885

  1. Degranulation patterns of eosinophils in advanced gastric carcinoma: an electron microscopic study.

    PubMed

    Caruso, R A; Ieni, A; Fedele, F; Zuccalà, V; Riccardo, M; Parisi, E; Parisi, A

    2005-01-01

    Recruitment and activation of eosinophils have been studied intensely in asthma and other allergic diseases. Less is known about the infiltration and degranulation patterns of eosinophils in the tumor stroma. Seven cases of advanced gastric carcinomas were found to be massively infiltrated by eosinophils and studied by light and electron microscopy. Gastric carcinomas, despite having similar numbers of tissue eosinophils, exhibited markedly different degranulation patterns. In 2 cases, resting nondegranulating eosinophils were found. Piecemeal degranulation was the predominant mode of secretion from eosinophils localized within the tumor stroma in 4 cases. Eosinophil exocytosis and cytolysis were rarely observed. In 1 case, crystals morphologically similar to Charcot-Leyden crystals were observed at the extracellular level as well as in phagosomes of tissue macrophages, confirming active sequestrations of eosinophil Charcot-Leyden protein by macrophages in vivo. In the same case, eosinophils showed characteristic features of early and late apoptotic changes, such as condensed chromatin, focal dilatation of nuclear envelope, and preserved plasma membrane. Morphological association between apoptotic eosinophils and deposition of granules in the tumor stroma was found. Extracellular deposition of intact granules from apoptotic eosinophils was distinct from eosinophilic (necrotic) cytolysis, and has reported previously in experimental studies in vitro. To the knowledge of the authors, this case represents the first report of late apoptotic eosinophils that release their granules within the tumor stroma in a human gastric carcinoma. PMID:15931778

  2. Clinical usefulness of mepolizumab in severe eosinophilic asthma.

    PubMed

    Menzella, Francesco; Lusuardi, Mirco; Montanari, Gloria; Galeone, Carla; Facciolongo, Nicola; Zucchi, Luigi

    2016-01-01

    Asthma is a chronic inflammatory disorder of the airways with variable clinical severity from very mild and occasional symptoms to recurrent critical exacerbations, at risk of fatal or near-fatal outcome, in a small percentage of patients. Within the different inflammatory cascades involved in asthma, eosinophils play a central role in the pathogenesis and largely influence disease severity. Interleukin-5 (IL-5) is the main cytokine controlling eosinophil activity and proliferation at the site of inflammation. Mepolizumab was the first biological humanized anti-IL-5 monoclonal antibody tested in randomized clinical trials on eosinophilic asthma and other eosinophilic diseases. On the basis of several positive clinical efficacy data, it has recently been approved by the US Food and Drug Administration for the treatment of severe eosinophilic asthma. Unfortunately, high costs are at present a critical issue. Future studies will probably help in the correct selection of a potential "responder phenotype", allowing the prescription of this promising therapy to appropriate patients and best define cost-effectiveness issues. PMID:27354806

  3. Eosinophilic esophagitis: New insights in pathogenesis and therapy.

    PubMed

    Guarino, Michele Pier Luca; Cicala, Michele; Behar, Jose

    2016-02-01

    Eosinophilic esophagitis (EoE) is a clinico-pathological entity with esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus that may persist despite treatment with proton pump inhibitors. This eosinophilic infiltration is usually absent in the stomach, small intestine and colon, although there are a number of reports of patients with a multi-organ involvement. EoE is associated with abnormalities involving TH2-dependent immunity, with multiple environmental factors strongly contributing to disease expression. The layer of the esophagus affected by the eosinophilic infiltration causes the specific symptoms. Esophageal involvement results mostly in dysphagia for solids that can be severe enough to cause recurrent esophageal obstruction with typical endoscopic features suggesting esophageal remodeling and pathological changes of eosinophilic infiltration of the mucosa, sub-epithelial fibrosis and muscle hypertrophy. This disease is frequently associated with other allergic conditions such as allergic asthma, allergic dermatitis and eosinophilia. The treatment of patients with EoE depends on the severity of the symptoms and of the inflammatory process as well as to their response to a gradual step-up treatment. The first line of treatment consists of steroid containing local inhalers. If unresponsive they are then treated with oral steroids. Intravenous interleukin blockers seem to have a consistent positive therapeutic effect. PMID:26855813

  4. Eosinophilic Myocarditis due to Toxocariasis: Not a Rare Cause

    PubMed Central

    Shibazaki, Shunichi; Eguchi, Shunsuke; Endo, Takashi; Wakabayashi, Tadamasa; Araki, Makoto; Gu, Yoshiaki; Imai, Taku; Asano, Kouji; Taniuchi, Norihide

    2016-01-01

    Myocarditis is a clinically important disease because of the high mortality. From the perspective of treatment strategy, eosinophilic myocarditis should be distinguished from other types of myocarditis. Toxocariasis, caused by Toxocara canis or Toxocara cati, is known as a cause of eosinophilic myocarditis but is considered rare. As it is an unpopular disease, eosinophilic myocarditis due to toxocariasis may be underdiagnosed. We experienced two cases of eosinophilic myocarditis due to toxocariasis from different geographical areas in quick succession between 2013 and 2014. Case 1 is 32-year-old man. Case 2 is 66-year-old woman. In both cases, diagnosis was done by endomyocardial biopsy and IgG-ELISA against Toxocara excretory-secretory antigen. Only a corticosteroid was used in Case  1, whereas a corticosteroid and albendazole were used in Case  2 as induction therapy. Both patients recovered. Albendazole was also used in Case  1 to prevent recurrence after induction therapy. Eosinophilic myocarditis by toxocariasis may in actuality not be a rare disease, and corticosteroid is an effective drug as induction therapy even before use of albendazole. PMID:27123346

  5. EDTA-dependent pseudothrombocytopenia complicated by eosinophilic pneumonia.

    PubMed

    Ohashi, Naoko; Nakamura, Kensuke; Inokuchi, Ryota; Sato, Hajime; Tokunaga, Kurato; Fukuda, Tatsuma; Nakajima, Susumu; Yahagi, Naoki

    2013-07-01

    EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is a phenomenon that occurs in vitro when EDTA reacts with harvested blood. EDTA-dependent pseudothrombocytopenia usually does not indicate thrombocytopenia in vivo. Here, we report the first case of EDTA-PTCP complicated by eosinophilic pneumonia. A 70-year-old man with rectal cancer was admitted to the hospital for a liver abscess and rectal cancer. At the time of admission, his platelet count was 20,000/μL, but a peripheral blood smear showed platelet aggregation and the platelet count for a kanamycin-added EDTA blood sample was 180,000/μL. The patient's respiratory status worsened after treatment for the liver abscess and rectal cancer. The patient's bronchoalveolar lavage contained 45% eosinophils, and a diagnosis of acute eosinophilic pneumonia was made. In recent studies, the occurrence of eosinophilic disease has been shown in idiopathic thrombocytopenic purpura. EDTA-dependent pseudothrombocytopenia is an in vitro phenomenon, although platelet activation that results in eosinophil invasion may occur in severe cases. PMID:23702069

  6. Bullous delayed pressure urticaria: pathogenic role for eosinophilic granulocytes?

    PubMed

    Kerstan, A; Rose, C; Simon, D; Simon, H-U; Bröcker, E-B; Trautmann, A; Leverkus, M

    2005-08-01

    Bullous delayed pressure urticaria (DPU) is a rare variant of DPU. Treatment of DPU is difficult and the underlying pathogenic mechanism of DPU remains elusive. We report a 72-year-old man with DPU and associated chronic urticaria as well as delayed urticarial dermographism. Pressure challenge gave rise to a deep weal covered by multiple vesicles and bullae after 24 h. Histological examination of a skin biopsy specimen obtained 24 h after pressure challenge demonstrated intraepidermal bullae filled with eosinophils accompanied by a dense, predominantly eosinophilic infiltrate in the dermis. Whereas the numbers and morphology of mast cells were unaltered, the extracellular deposition of eosinophil cationic protein revealed evidence for eosinophil activation. Concomitantly, both CD4+ and CD8+ T lymphocytes were present in the infiltrate and expressed interleukin 5. As bullous DPU may represent the maximal variant of DPU, the investigation of the cellular infiltrate and the chemokines/cytokines released may reveal potential pathogenic mechanisms. A possible effector role of eosinophilic granulocytes, T-cell subsets and mast cells is discussed. PMID:16086763

  7. Familial aggregation and segregation analysis of eosinophil levels.

    PubMed

    Holberg, C J; Halonen, M; Wright, A L; Martinez, F D

    1999-11-01

    The number of circulating eosinophils is associated with the risk of asthma in population samples. Therefore, eosinophil levels may be an intermediate phenotype for asthma amenable to genetic analysis. We examined familial aggregation of the number of eosinophils x 10(6) L(-1) and the percentage of eosinophils based on a 300 count differential in 644 Hispanic and non-Hispanic white families, with 2, 097 subjects, enrolled in the Tucson Children's Respiratory Study. Both measures were adjusted for age, season and year at the time blood was drawn, sex, and ethnicity. Segregation analysis was conducted in the 458 non-Hispanic white families, as there were no significant familial correlations in the Hispanic families, and there was significant heterogeneity by ethnic group. Familial correlations (rho) in the non-Hispanic white families were as follows: mother-father, 0.05; mother-child, 0.18 (p < 0.001); father-child, 0.07; sibling-sibling, 0.31 (p < 0.001). Without covariates analyses indicated a polygenic/multifactorial mode of inheritance. After adjusting for current and past asthma an oligogenic mode of inheritance was suggested, plus additional residual familial components that were mainly maternally mediated. This study supports the notion of multiple, relatively common genes interacting to determine genetic susceptibility to asthma. Holberg CJ, Halonen M, Wright AL, Martinez FD. Familial aggregation and segregation analysis of eosinophil levels. PMID:10556128

  8. Integrins are Mechanosensors That Modulate Human Eosinophil Activation

    PubMed Central

    Ahmadzai, Mustafa; Small, Mike; Sehmi, Roma; Gauvreau, Gail; Janssen, Luke J.

    2015-01-01

    Eosinophil migration to the lung is primarily regulated by the eosinophil-selective family of eotaxin chemokines, which mobilize intracellular calcium (Ca2+) and orchestrate myriad changes in cell structure and function. Eosinophil function is also known to be flow-dependent, although the molecular cognate of this mechanical response has yet to be adequately characterized. Using confocal fluorescence microscopy, we determined the effects of fluid shear stress on intracellular calcium concentration ([Ca2+]i) in human peripheral blood eosinophils by perfusing cells in a parallel-plate flow chamber. Our results indicate that fluid perfusion evokes a calcium response that leads to cell flattening, increase in cell area, shape change, and non-directional migration. None of these changes are seen in the absence of a flow stimulus, and all are blocked by chelation of intracellular Ca2+ using BAPTA. These changes are enhanced by stimulating the cells with eotaxin-1. The perfusion-induced calcium response (PICR) could be blocked by pre-treating cells with selective (CDP-323) and non-selective (RGD tripeptides) integrin receptor antagonists, suggesting that α4β7/α4β1 integrins mediate this response. Overall, our study provides the first pharmacological description of a molecular mechanosensor that may collaborate with the eotaxin-1 signaling program in order to control human eosinophil activation. PMID:26539194

  9. Diagnosis and Treatment of Eosinophilic Esophagitis in Adults.

    PubMed

    Kavitt, Robert T; Hirano, Ikuo; Vaezi, Michael F

    2016-09-01

    Eosinophilic esophagitis is a relatively recently discovered disease of increasing incidence and prevalence and is a common cause of dysphagia and food bolus impaction. The definition of eosinophilic esophagitis continues to evolve, most recently with the characterization of proton pump inhibitor-responsive esophageal eosinophilia. The number of high-quality prospective, controlled trials guiding therapeutic decisions in eosinophilic esophagitis has increased steadily over the past several years. Treatment options at present focus on dietary therapy, particularly implementation of a 6-food elimination diet, and medical therapy, primarily the use of swallowed, topical corticosteroids. Proton pump inhibitors play an important role in current management. Conservative esophageal dilation is effective at ameliorating dysphagia in symptomatic patients with esophageal strictures. We conducted an evidence-based review of the diagnosis and treatment options in adults with eosinophilic esophagitis. The understanding of eosinophilic esophagitis continues to be refined. Continued validation of appropriate endpoints, however, is essential to establish the efficacy of existing and novel therapeutic approaches. PMID:27155108

  10. Activated mouse eosinophils protect against lethal respiratory virus infection

    PubMed Central

    Percopo, Caroline M.; Dyer, Kimberly D.; Ochkur, Sergei I.; Luo, Janice L.; Fischer, Elizabeth R.; Lee, James J.; Lee, Nancy A.; Domachowske, Joseph B.

    2014-01-01

    Eosinophils are recruited to the airways as a prominent feature of the asthmatic inflammatory response where they are broadly perceived as promoting pathophysiology. Respiratory virus infections exacerbate established asthma; however, the role of eosinophils and the nature of their interactions with respiratory viruses remain uncertain. To explore these questions, we established acute infection with the rodent pneumovirus, pneumonia virus of mice (PVM), in 3 distinct mouse models of Th2 cytokine–driven asthmatic inflammation. We found that eosinophils recruited to the airways of otherwise naïve mice in response to Aspergillus fumigatus, but not ovalbumin sensitization and challenge, are activated by and degranulate specifically in response to PVM infection. Furthermore, we demonstrate that activated eosinophils from both Aspergillus antigen and cytokine-driven asthma models are profoundly antiviral and promote survival in response to an otherwise lethal PVM infection. Thus, although activated eosinophils within a Th2-polarized inflammatory response may have pathophysiologic features, they are also efficient and effective mediators of antiviral host defense. PMID:24297871

  11. Eosinophilic esophagitis: New insights in pathogenesis and therapy

    PubMed Central

    Guarino, Michele Pier Luca; Cicala, Michele; Behar, Jose

    2016-01-01

    Eosinophilic esophagitis (EoE) is a clinico-pathological entity with esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus that may persist despite treatment with proton pump inhibitors. This eosinophilic infiltration is usually absent in the stomach, small intestine and colon, although there are a number of reports of patients with a multi-organ involvement. EoE is associated with abnormalities involving TH2-dependent immunity, with multiple environmental factors strongly contributing to disease expression. The layer of the esophagus affected by the eosinophilic infiltration causes the specific symptoms. Esophageal involvement results mostly in dysphagia for solids that can be severe enough to cause recurrent esophageal obstruction with typical endoscopic features suggesting esophageal remodeling and pathological changes of eosinophilic infiltration of the mucosa, sub-epithelial fibrosis and muscle hypertrophy. This disease is frequently associated with other allergic conditions such as allergic asthma, allergic dermatitis and eosinophilia. The treatment of patients with EoE depends on the severity of the symptoms and of the inflammatory process as well as to their response to a gradual step-up treatment. The first line of treatment consists of steroid containing local inhalers. If unresponsive they are then treated with oral steroids. Intravenous interleukin blockers seem to have a consistent positive therapeutic effect. PMID:26855813

  12. Clinical usefulness of mepolizumab in severe eosinophilic asthma

    PubMed Central

    Menzella, Francesco; Lusuardi, Mirco; Montanari, Gloria; Galeone, Carla; Facciolongo, Nicola; Zucchi, Luigi

    2016-01-01

    Asthma is a chronic inflammatory disorder of the airways with variable clinical severity from very mild and occasional symptoms to recurrent critical exacerbations, at risk of fatal or near-fatal outcome, in a small percentage of patients. Within the different inflammatory cascades involved in asthma, eosinophils play a central role in the pathogenesis and largely influence disease severity. Interleukin-5 (IL-5) is the main cytokine controlling eosinophil activity and proliferation at the site of inflammation. Mepolizumab was the first biological humanized anti-IL-5 monoclonal antibody tested in randomized clinical trials on eosinophilic asthma and other eosinophilic diseases. On the basis of several positive clinical efficacy data, it has recently been approved by the US Food and Drug Administration for the treatment of severe eosinophilic asthma. Unfortunately, high costs are at present a critical issue. Future studies will probably help in the correct selection of a potential “responder phenotype”, allowing the prescription of this promising therapy to appropriate patients and best define cost-effectiveness issues. PMID:27354806

  13. Fecal microbiota transplantation and prednisone for severe eosinophilic gastroenteritis

    PubMed Central

    Dai, Yi-Xuan; Shi, Chuan-Bing; Cui, Bo-Ta; Wang, Min; Ji, Guo-Zhong; Zhang, Fa-Ming

    2014-01-01

    Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations. We describe a case of severe eosinophilic gastroenteritis presenting as frequent bowel obstruction and diarrhea in a 35-year-old man. The patient was misdiagnosed and underwent surgery because of intestinal obstruction when he was first admitted to a local hospital. Then he was misdiagnosed as having Crohn’s disease in another university teaching hospital. Finally, the patient asked for further treatment from our hospital because of the on-going clinical trial for treating refractory Crohn’s disease by fecal microbiota transplantation. Physical examination revealed a slight distended abdomen with diffuse tenderness. Laboratory investigation showed the total number of normal leukocytes with neutrophilia as 90.5%, as well as eosinopenia, monocytopenia and lymphocytopenia. Barium radiography and sigmoidoscopy confirmed inflammatory stenosis of the sigmoid colon. We diagnosed the patient as having eosinophilic gastroenteritis by multi-examinations. The patient was treated by fecal microbiota transplantation combined with oral prednisone, and was free from gastrointestinal symptoms at the time when we reported his disease. This case highlights the importance of awareness of manifestations of a rare disease like eosinophilic gastroenteritis. PMID:25473198

  14. Unusual presentations of eosinophilic gastroenteritis: two case reports.

    PubMed

    Leal, Regina; Fayad, Leonardo; Vieira, Daniella; Figueiredo, Teresa; Lopes, Aldemae; Carvalho, Roberta; Dantas-Corrêa, Esther; Schiavon, Leonardo; Narciso-Schiavon, Janaína

    2014-06-01

    Eosinophilic gastroenteritis is a rare disease that is characterized by eosinophil infiltration in one or multiple segments of the gastrointestinal tract. The etiology of this condition remains unknown. Eosinophilic gastroenteritis has heterogeneous clinical manifestations that depend upon the location and depth of infiltration in the gastrointestinal tract, and eosinophilia may or may not be present. This article reports two cases of eosinophilic gastroenteritis. The first is that of a 49-year-old woman with abdominal pain, ascites, eosinophilia, and a history of asthma. The second case is that of a 69-year-old male with a history of loss of appetite, belching, postprandial fullness, heartburn, and a 5-kilogram weight loss over a period of 9 months; ultimately, the patient was diagnosed with a gastric outlet obstruction due to pyloric stenosis. The rare character of eosinophilic gastroenteritis and its varied clinical presentations often lead to delayed diagnoses and complications. Case reports may help to disseminate knowledge about the disease, thereby increasing the likelihood of early diagnosis and intervention to prevent complications. PMID:25141324

  15. Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo

    PubMed Central

    Chu, Derek K.; Jimenez-Saiz, Rodrigo; Verschoor, Christopher P.; Walker, Tina D.; Goncharova, Susanna; Llop-Guevara, Alba; Shen, Pamela; Gordon, Melissa E.; Barra, Nicole G.; Bassett, Jennifer D.; Kong, Joshua; Fattouh, Ramzi; McCoy, Kathy D.; Bowdish, Dawn M.; Erjefält, Jonas S.; Pabst, Oliver; Humbles, Alison A.; Kolbeck, Roland; Waserman, Susan

    2014-01-01

    Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4+/+ or il4−/− eosinophils. Eosinophils controlled CD103+ dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity. PMID:25071163

  16. Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo.

    PubMed

    Chu, Derek K; Jimenez-Saiz, Rodrigo; Verschoor, Christopher P; Walker, Tina D; Goncharova, Susanna; Llop-Guevara, Alba; Shen, Pamela; Gordon, Melissa E; Barra, Nicole G; Bassett, Jennifer D; Kong, Joshua; Fattouh, Ramzi; McCoy, Kathy D; Bowdish, Dawn M; Erjefält, Jonas S; Pabst, Oliver; Humbles, Alison A; Kolbeck, Roland; Waserman, Susan; Jordana, Manel

    2014-07-28

    Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils. Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity. PMID:25071163

  17. Recent Progress in the Research of Eosinophilic Esophagitis and Gastroenteritis.

    PubMed

    Kinoshita, Yoshikazu; Ishimura, Norihisa; Oshima, Naoki; Mikami, Hironobu; Okimoto, Eiko; Jiao, Di Jin; Ishihara, Shunji

    2016-01-01

    Eosinophilic esophagitis (EoE) and gastroenteritis are allergic gastrointestinal diseases mainly caused by food allergens. The number of patients with EoE is rapidly increasing in both Western and Asian countries. Basic knowledge of these diseases has mainly come from studies of EoE and Th2 type allergic reactions, including IL-5, IL-13, and IL-15, thymic stromal protein, and eotaxin 3, which are considered to have important roles. For a diagnosis of EoE, endoscopic abnormalities and histological confirmation of dense eosinophile infiltration in the esophageal epithelial layer are important, in addition to identifying dysphagia symptoms. As for eosinophilic gastroenteritis, blood test findings are more useful and the role of an endoscopic examination is reduced. For both diseases, the infection rate of Helicobacter pylori is lower than in healthy controls. Glucocorticoid administration is standard treatment for these diseases, while proton pump inhibitors are frequently effective for EoE. PMID:26789117

  18. Diagnostic approach to eosinophilic oesophagitis: Pearls and pitfalls.

    PubMed

    Schoepfer, Alain

    2015-10-01

    Eosinophilic oesophagitis (EoE) has first been described a little over 20 years ago. EoE has been defined by a panel of international experts as a "chronic, immune/antigen-mediated, oesophageal disease, characterized clinically by symptoms related to oesophageal dysfunction and histologically by eosinophil-predominant inflammation". A value of ≥ 15 eosinophils has been defined as histologic diagnostic cutoff. Other conditions associated with oesophageal eosinophilia, such as gastro-oesophageal reflux disease (GERD), PPI-responsive oesophageal eosinophilia, or Crohn's disease should be excluded before EoE can be diagnosed. This review highlights the latest insights regarding the diagnosis and differential diagnosis of EoE. PMID:26552777

  19. A case of an unexplained eosinophilic myocarditis in a dog.

    PubMed

    Keeshen, T P; Chalkley, M; Stauthammer, C

    2016-09-01

    An 8-year-old spayed female Munsterlander was evaluated for a chronic low grade fever and a two month history of exercise intolerance. On physical examination, tachycardia and a grade II/VI right systolic heart murmur were detected. Echocardiography revealed marked thickening of the atrial and ventricular walls with mixed echogenicity and concentric hypertrophy of the left and right ventricles and equivocal systolic dysfunction. Serum cardiac troponin I level was markedly elevated. Endomyocardial biopsy was attempted; however, the patient arrested during the procedure and resuscitation was unsuccessful. Post-mortem examination revealed severe, chronic atrial and ventricular eosinophilic myocarditis associated with marked interstitial fibrosis. Serological testing, histopathology and immunohistochemistry staining did not reveal an underlying infectious agent or neoplasm. To our knowledge, this is the first reported case of primary eosinophilic myocarditis in the absence of a peripheral eosinophilia and multi-organ eosinophilic inflammation in a dog. PMID:27170173

  20. Heparin reduces nonspecific eosinophil staining artifacts in mass cytometry experiments.

    PubMed

    Rahman, Adeeb H; Tordesillas, Leticia; Berin, M Cecilia

    2016-06-01

    The analysis of heterogeneous cell samples by mass cytometry (CyTOF) relies on the assumption that metal labeled antibodies accurately bind to their target antigens. We report a previously unappreciated experimental artifact of non-specific antibody binding by eosinophils during intracellular CyTOF analysis of human whole blood samples. We hypothesized that this non-specific binding results from a charge-based interaction between the metal-labeled antibodies and highly cationic proteins found in eosinophillic granules and found that this non-specific staining artifact could be reduced to background levels with a simple blocking protocol using heparin as a competing anionic protein. This protocol eliminates a potential source of erroneous data interpretation in all experiments involving intracellular staining of human whole blood samples, and allows accurate assessment of dynamic changes in intracellular proteins in eosinophils by CyTOF. © 2016 International Society for Advancement of Cytometry. PMID:27061608

  1. Eosinophilic ulcer of the tongue--Case report.

    PubMed

    Didona, Dario; Paolino, Giovanni; Donati, Michele; Didona, Biagio; Calvieri, Stefano

    2015-01-01

    Eosinophilic ulcer of the oral mucosa is a rare, self-limiting, chronic and benign lesion of unknown pathogenesis that affects the oral mucosa. We present the case of a 65 year-old Caucasian female with a five month history of a painful ulcer on the lateral side of her tongue. The ulcer was not adhered to the underlying structures and there was no evidence of regional lymph node involvement. Laboratory examinations and X-rays revealed no abnormalities. Topical treatments had been performed without any improvement. Histopathological examination showed an ulcerated surface and mixed inflammatory infiltrate with several eosinophils extending into the mucosa and submucosa. No cellular atypia was observed. Based on the patient-s history and mucosal biopsy, a final diagnosis of eosinophilic ulcer of the oral mucosa was made. PMID:26312683

  2. Eosinophilic pancreatitis: Three case reports and literature review

    PubMed Central

    TIAN, LIN; FU, PENG; DONG, XIANGHUI; QI, JIPING; ZHU, HONG

    2016-01-01

    Eosinophilic pancreatitis (EP) is a rare form of chronic pancreatitis characterized by localized or diffuse eosinophilic infiltration of the pancreas and elevated serum immunoglobulin E levels. EP is difficult to distinguish from pancreatic cancer on the basis of clinical symptoms and the results of auxiliary examination alone. A retrospective analysis of the clinicopathological characteristics and laboratory, imaging, and pathology results of 3 patients with EP, who were initially diagnosed with pancreatic malignancy, was performed. EP is an allergic disease with non-specific clinical manifestations that is difficult to distinguish from pancreatic cancer based exclusively on clinical symptoms and auxiliary examination, resulting in the need for invasive procedures to confirm the diagnosis. An increase in the eosinophil count in the peripheral blood and pathological examination are essential for the diagnosis of EP. PMID:27073662

  3. Childhood-onset eosinophilic granulomatosis with polyangiitis: a rare childhood vasculitis mimicking anthrax and eosinophilic leukaemia.

    PubMed

    Sahin, Sezgin; Adrovic, Amra; Barut, Kenan; Kasapcopur, Ozgur

    2016-01-01

    A 14-year-old boy previously misdiagnosed as having cutaneous anthrax was referred with a 2-month history of multiple wide and deep ulceronecrotic lesions in the lower extremities, which occurred after contact with animals. Skin biopsy was compatible with vasculitis. Further examination at our hospital elicited eosinophilia and a history of asthma. On the second day of hospitalisation, he developed deep vein thrombosis. A diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) was established and intravenous methylprednisolone was administered. The patient showed remarkable improvement of the cutaneous lesions. Diagnosis of EGPA is challenging in the vasculitic phase and necessitates a detailed history that specifically questions the patient for an asthma background. This case illustrates a severe cutaneous presentation of EGPA and emphasises the difficulty of diagnosis as a result of overlapped signs and symptoms with cutaneous anthrax and leukaemia. EGPA should be kept in mind in the differential diagnosis of cutaneous lesions associated with eosinophilia. PMID:26887883

  4. Role of Eosinophil Granulocytes in Allergic Airway Inflammation Endotypes.

    PubMed

    Amin, K; Janson, C; Bystrom, J

    2016-08-01

    Eosinophil granulocytes are intriguing members of the innate immunity system that have been considered important defenders during parasitic diseases as well as culprits during allergy-associated inflammatory diseases. Novel studies have, however, found new homoeostasis-maintaining roles for the cell. Recent clinical trials blocking different Th2 cytokines have uncovered that asthma is heterogeneous entity and forms different characteristic endotypes. Although eosinophils are present in allergic asthma with early onset, the cells may not be essential for the pathology. The cells are, however, likely disease causing in asthma with a late onset, which is often associated with chronic rhinosinusitis. Assessment of eosinophilia, fraction exhaled nitric oxide (FeNO) and periostin are markers that have emerged useful in assessing and monitoring asthma severity and endotype. Current scientific knowledge suggests that eosinophils are recruited by the inflammatory environment, activated by the innate interleukin (IL)-33 and prevented from apoptosis by both lymphocytes and innate immune cells such as type two innate immune cells. Eosinophils contain four specific granule proteins that exhibit an array of toxic and immune-modulatory activates. The granule proteins can be released by different mechanisms. Additionally, eosinophils contain a number of inflammatory cytokines and lipid mediators as well as radical oxygen species that might contribute to the disease both by the recruitment of other cells and the direct damage to supporting cells, leading to exacerbations and tissue fibrosis. This review aimed to outline current knowledge how eosinophils are recruited, activated and mediate damage to tissues and therapies used to control the cells. PMID:27167590

  5. Unsedated transnasal esophagoscopy for monitoring therapy in pediatric eosinophilic esophagitis

    PubMed Central

    Friedlander, Joel A.; DeBoer, Emily M.; Soden, Jason S.; Furuta, Glenn T.; Menard-Katcher, Calies D.; Atkins, Dan; Fleischer, David M.; Kramer, Robert E.; Deterding, Robin R.; Capocelli, Kelley E.; Prager, Jeremy D.

    2015-01-01

    Background and Aims Unsedated transnasal endoscopy (TNE) is safer and less costly than sedated EGD. The aim of this study was to evaluate the performance of TNE with biopsies in monitoring the esophageal mucosa of pediatric patients with eosinophilic esophagitis. Methods Patients between 8 and 17 years of age with eosinophilic esophagitis and their parents were enrolled. Unsedated TNE was performed. A 2.8-mm (1.2-mm channel) or a 4-mm flexible bronchoscope (2-mm channel) was used, and esophageal biopsy specimens were obtained. Biopsy specimen analysis, duration, adverse events, and billing charges of TNE were assessed. Immediately after TNE and a minimum of 2 weeks later, a modified Group Health Association of America 9 survey and a preference questionnaire were completed, respectively. Results Twenty-one of 22 enrolled patients underwent TNE. TNE was performed with no serious adverse events. Histopathological analysis revealed 0 eosinophils per high-power field (n = 12), fewer than 15 eosinophils per high-power field (n = 4), and more than 15 eosinophils per high-power field (n = 5). The total epithelial surface area of mucosal biopsy samples from either TNE Forceps (1.2 mm or 2 mm biopsy channel forceps) compared with those obtained during the subject’s previous EGD by using standard endoscopic forceps was not statistically different (P = .308 [1.2 mm]/P = .492 [2 mm]). All parents and 76.2% of subjects would undergo the TNE again. TNE was preferred over EGD by 85.7% of parents and 52.4% of subjects. The modified Group Health Association of America 9 survey revealed a high degree of satisfaction (average, 43.19 ± 2.6; maximum score, 45). Charges associated with TNE were 60.1% lower than for previous EGDs. Conclusions Unsedated TNE is an effective, lower-cost procedure for monitoring the esophageal mucosa of children with eosinophilic esophagitis. PMID:26142551

  6. Chronic eosinophilic leukemia in a cat: cytochemical and immunophenotypical features.

    PubMed

    Gelain, Maria Elena; Antoniazzi, Elisa; Bertazzolo, Walter; Zaccolo, Maurizia; Comazzi, Stefano

    2006-12-01

    A 3-year-old, male, domestic shorthaired cat was presented with a 3-day history of anorexia and depression. The cat was moderately dehydrated, had pale, slightly icteric, mucous membranes, oral ulcerations, and mild hepatosplenomegaly. A feline leukemia virus (FeLV) antigen test was positive. CBC results obtained at initial presentation included severe normocytic, normochromic, nonregenerative anemia, severe thrombocytopenia, and marked leukocytosis (>100,000/microL) with 77% eosinophils. After 15 days of treatment with prednisone and doxycycline, the cat had persistent severe nonregenerative anemia (HCT 3.4%), thrombocytopenia (28,000/microL), and extreme eosinophilia (total eosinophils, 123.1 x 10(3)/microL; segmented 103.0 x 10(3)/microL; immature 20.1 X 10(3)/microL). Cytologic examination of aspirates from bone marrow, liver, lymph nodes, and spleen revealed a predominance of mature and immature eosinophils, many with dysplastic changes. The M:E ratio was 96.4. On histopathologic examination, multiple organs were infiltrated by eosinophilic granulocytes. Neoplastic cells in blood and bone marrow stained positive for alkaline phosphatase and were negative for myeloperoxidase, chloroacetate esterase, and alpha-naphthyl acetate esterase. On flow cytometric analysis of peripheral blood, the neoplastic cells were positive for CD11b and CD14. These findings were consistent with chronic eosinophilic leukemia. To our knowledge, this is the first report of chronic eosinophilic leukemia in a cat associated with naturally acquired FeLV infection, in which flow cytometry was used to characterize the neoplastic cells. PMID:17123254

  7. Primary Eosinophilic Gastritis in a Child with Gastric Outlet Obstruction.

    PubMed

    Katiyar, Richa; Patne, Shashikant C U; Dixit, Vinod Kumar; Sharma, Shiv Prasad

    2016-06-01

    A 3-year-old girl presented with multiple episodes of vomiting, fever, and hematemesis for the past 2 months. Except for hemoglobin, her rests of the laboratory tests were unremarkable. Her barium X-ray showed absence of the duodenal bulb and the C-loop. Her endoscopy showed deformed stomach with multiple ulcers and diverticuli. The gastric outlet was not visualized. Distal gastrectomy with gastro-duodenal anastomosis was performed. Histopathological findings revealed transmural dense infiltrates of eosinophils, consistent with eosinophilic gastritis. PMID:26768007

  8. Recent advances in the recognition and management of eosinophilic esophagitis

    PubMed Central

    Eustace, Gregory; Gui, Xianyong; Iacucci, Marietta

    2015-01-01

    The incidence and recognition of eosinophilic esophagitis is increasing. Pathophysiological understanding of eosinophilic esophagitis is improving and an immunological reaction to ingested food is likely to play a significant role. Patients present with dysphagia and food bolus obstruction. Both histological and endoscopic criteria have been developed and validated. Dietary therapy, topical steroid therapy, proton pump inhibitors and endoscopic dilation are the main approaches to therapy; however, novel targeted therapies are being developed. Among the food items commonly implicated are wheat, dairy, nuts, soy, shellfish and eggs. A multidisciplinary approach to management in dedicated clinics may yield the best results. PMID:26076223

  9. Spontaneous intramural esophageal dissection: an unusual onset of eosinophilic esophagitis.

    PubMed

    Ibáñez-Sanz, Gemma; Rodríguez Alonso, Lorena; Romero Martínez, Natalia M

    2016-03-01

    A 35-year-old man, with a history of rhinitis, eczema and a dubious achalasia was admitted due to chest pain and sialorrhea. Upper endoscopy showed a little hole and a narrowing of the distal esophagus. A CT-scan with oral contrast exposed a discontinuity of the lumen of the middle third of the esophagus and a dissection of submucosal space 16 cm long. The patient recovered after parenteral nutrition. After four months, an esophageal endoscopic showed transient whitish exudates, longitudinal furrows and esophageal lacerations. The biopsies illustrated significant eosinophilic inflammation, eosinophilic microabscesses and basal cell hyperplasia. PMID:26949147

  10. Eosinophilic esophagitis as paraneoplastic syndrome in a patient with ganglioneuroblastoma.

    PubMed

    Prader, S; Spalinger, J; Caduff, J; Hürlimann, S; Rischewski, J

    2015-05-01

    A 16-month-old boy presented with failure to thrive despite sufficient caloric intake, hypersalivation, abdominal pain, chronic diarrhea and blepharitis. An eosinophilic esophagitis (EoE) was diagnosed by esophageal biopsy. Dietary restrictions and topical steroid treatment lead to no improvement. Further diagnostic work-up revealed an intrathoracal, paraspinal ganglioneuroblastoma. After operative extirpation of the tumour, all initial symptoms resolved. An esophageal control biopsy 4 weeks after tumour resection was normal. This is the first report of eosinophilic esophagitis as part of a paraneoplastic syndrome in a patient with a malignant disease other than a carcinoma. PMID:25985452