Eosinophils in Autoimmune Diseases

Directory of Open Access Journals (Sweden)

Daniela Čiháková

2017-04-01

Full Text Available Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

Eosinophils in Autoimmune Diseases

Science.gov (United States)

Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

2017-01-01

Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

Proteomics of Eosinophil Activation

Directory of Open Access Journals (Sweden)

Deane F. Mosher

2017-09-01

Full Text Available We recently identified and quantified >7,000 proteins in non-activated human peripheral blood eosinophils using liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS and described phosphoproteomic changes that accompany acute activation of eosinophils by interleukin-5 (IL5 (1. These data comprise a treasure trove of information about eosinophils. We illustrate the power of label-free LC–MS/MS quantification by considering four examples: complexity of eosinophil STATs, contribution of immunoproteasome subunits to eosinophil proteasomes, complement of integrin subunits, and contribution of platelet proteins originating from platelet–eosinophil complexes to the overall proteome. We describe how isobaric labeling enables robust sample-to-sample comparisons and relate the 220 phosphosites that changed significantly upon treatment with IL5 to previous studies of eosinophil activation. Finally, we review previous attempts to leverage the power of mass spectrometry to discern differences between eosinophils of healthy subjects and those with eosinophil-associated conditions and point out features of label-free quantification and isobaric labeling that are important in planning future mass spectrometric studies.

Eosinophilic Mucin Otomastoiditis and Otopolyposis: A Progressive Form of Eosinophilic Otitis Media.

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Azadarmaki, Roya; Westra, William; Prasad, Sanjay

2015-09-01

The purpose of this study is to introduce and define a disease entity on a continuum of eosinophilic otitis media: eosinophilic mucin otomastoiditis and otopolyposis. A case of a 66-year-old woman with complicated chronic otitis media is reported. A literature review of the National Library of Medicine's online database, with a focus on eosinophilic otitis media and eosinophilic mucin rhinosinusitis, was performed. The authors report the case of a 66-year-old woman with a history of asthma, chronic rhinosinusitis, nasal polyposis, and chronic otitis media who presented with allergic middle ear mucin and otic polyps. Treatment involved a tympanomastoidectomy with removal of otic polyps and steroid therapy. Eosinophilic mucin otomastoiditis with otopolyposis is a disease entity on a continuum of eosinophilic otitis media. This disease process shares similarities with eosinophilic mucin rhinosinusitis. Otic polypectomy and steroids are suggested therapeutic measures. © The Author(s) 2015.

IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration.

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Johansson, M W; Khanna, M; Bortnov, V; Annis, D S; Nguyen, C L; Mosher, D F

2017-10-01

IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod," which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators. Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin. Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed. After 10 minutes in the presence of IL-5, adherent eosinophils were polarized with PSGL-1 at the nucleopod tip and F-actin distributed diffusely at the opposite end. After 30-60 minutes, the nucleopod had dissipated such that PSGL-1 was localized in a crescent or ring away from the cell periphery, and F-actin was found in podosome-like structures. The periostin layer, detected with monoclonal antibody Stiny-1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase previously implicated in asthma pathogenesis. ADAM8 was not found in podosome-like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti-ADAM8 inhibited migration of IL-5-stimulated eosinophils on periostin. Migrating IL-5-activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny-1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate

Eosinophils from eosinophilic oesophagitis patients have T cell suppressive capacity and express FOXP3.

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Lingblom, C; Wallander, J; Ingelsten, M; Bergquist, H; Bove, M; Saalman, R; Welin, A; Wennerås, C

2017-03-01

Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (T regs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of T regs , was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in T regs . To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE. © 2016 British Society for Immunology.

Eosinophils.

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Radonjic-Hösli, Susanne; Simon, Hans-Uwe

2014-01-01

In 1846, T. Wharton-Jones described a coarsely granular stage in the development of granulocytic cells in animal and human blood. Shortly thereafter, Max Schultze redefined the coarsely granular cells as a type distinct from finely granular cells, rather than just a developmental stage. It was, however, not until 1879, when Paul Ehrlich introduced a method to distinguish granular cells by the staining properties of their granules, that a classification became possible. An intensive staining for eosin, among other aniline dyes, was eponymous for the coarsely granular cell type, which thereupon became referred to as eosinophil granulocyte. Eosinophilia had already been described in many diseases by the late 19th century. The role of these cells, however, today remains a matter of continuing speculation and investigation. Many functions have been attributed to the eosinophil over the years, often linked to increasing knowledge about the granular and cytoplasmatic contents. A better understanding of the regulatory mechanisms of eosinopoiesis has led to the development of knock-out mice strains as well as therapeutic strategies for reducing the eosinophil load in patients. The effect of these therapeutics and the characterization of the knock-out phenotypes have led to a great increase in the knowledge of the role of the eosinophil in disease. Today we think of the eosinophil as a multifunctional cell involved in host defense, tissue damage and remodeling, as well as immunomodulation. © 2014 S. Karger AG, Basel.

Sinusitis with eosinophilic otitis media

International Nuclear Information System (INIS)

Kawano, Toshiro; Ishitoya, Junichi; Tsukuda, Mamoru

2007-01-01

Eosinophilic otitis media is an intractable inflammation of the middle ear combined with bronchial asthma. According to a national epidemiological investigation on eosinophilic otitis media, it is assumed that eosinophilic otitis media are combined with sinusitis in about 74% of their cases. On the other hand, organizational images of eosinophilic otitis media and eosinophilic sinusitis are similar, and steroid therapy is effective together, and it is thought that they are involved in the idea of one airway one disease, but the details of sinusitis combined with the eosinophilic otitis media are unidentified. Therefore, we examined the kinds of the sinusitis combined with eosinophilic otitis media. We diagnosed 18 cases (male: 2 cases, female: 16 cases) (average age: 54.6 years old) as eosinophilic otitis media according to the diagnostic criteria. And, by the CT views of a paranasal sinus, blood tests, existence of the nasal polyp, etc, we investigated the kinds of sinusitis combined with eosinophilic otitis media. It turned out that bronchial asthma was combined with eosinophilic otitis media in 17 of 18 cases (airway hypersensitivity did sthenia of one case, but the asthma did not yet developed), and 6 cases were combined with aspirin induced asthma (AIA), and 3 cases were combined with Churg-Strauss syndromes (CSS). 10 case (55.6%) of 17 eosinophilic otitis media were combined with eosinophilic sinusitis. And 4 cases (22.2%) of 17 eosinophilic otitis media were combined with chronic sinusitis, 4 cases (22.2%) of 17 eosinophilic otitis media were not combined with sinusitis. We concluded that eosinophilic otitis media was not always combined with eosinophilic sinusitis. The idea of one airway one disease was not applied to this examination. (author)

Sinusitis with eosinophilic otitis media

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Kawano, Toshiro; Ishitoya, Junichi [Yokohama City Univ., Medical Center, Yokohama, Kanagawa (Japan); Tsukuda, Mamoru [Yokohama City Univ., Graduate School of Medicine, Yokohama, Kanagawa (Japan)

2007-09-15

Eosinophilic otitis media is an intractable inflammation of the middle ear combined with bronchial asthma. According to a national epidemiological investigation on eosinophilic otitis media, it is assumed that eosinophilic otitis media are combined with sinusitis in about 74% of their cases. On the other hand, organizational images of eosinophilic otitis media and eosinophilic sinusitis are similar, and steroid therapy is effective together, and it is thought that they are involved in the idea of one airway one disease, but the details of sinusitis combined with the eosinophilic otitis media are unidentified. Therefore, we examined the kinds of the sinusitis combined with eosinophilic otitis media. We diagnosed 18 cases (male: 2 cases, female: 16 cases) (average age: 54.6 years old) as eosinophilic otitis media according to the diagnostic criteria. And, by the CT views of a paranasal sinus, blood tests, existence of the nasal polyp, etc, we investigated the kinds of sinusitis combined with eosinophilic otitis media. It turned out that bronchial asthma was combined with eosinophilic otitis media in 17 of 18 cases (airway hypersensitivity did sthenia of one case, but the asthma did not yet developed), and 6 cases were combined with aspirin induced asthma (AIA), and 3 cases were combined with Churg-Strauss syndromes (CSS). 10 case (55.6%) of 17 eosinophilic otitis media were combined with eosinophilic sinusitis. And 4 cases (22.2%) of 17 eosinophilic otitis media were combined with chronic sinusitis, 4 cases (22.2%) of 17 eosinophilic otitis media were not combined with sinusitis. We concluded that eosinophilic otitis media was not always combined with eosinophilic sinusitis. The idea of one airway one disease was not applied to this examination. (author)

Case report

African Journals Online (AJOL)

abp

2015-12-02

Dec 2, 2015 ... Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net) ... The World Health Organization classifies liposarcomas into 5 histologic ... abundant eosinophil and fibrillary cytoplasm.

MHC Class II and CD9 in Human Eosinophils Localize to Detergent-Resistant Membrane Microdomains

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Akuthota, Praveen; Melo, Rossana C. N.; Spencer, Lisa A.

2012-01-01

Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor–stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR–containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4+ T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils. PMID:21885678

MHC Class II and CD9 in human eosinophils localize to detergent-resistant membrane microdomains.

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Akuthota, Praveen; Melo, Rossana C N; Spencer, Lisa A; Weller, Peter F

2012-02-01

Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor-stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR-containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4(+) T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils.

Evidence for a role of eosinophils in blister formation in bullous pemphigoid.

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de Graauw, E; Sitaru, C; Horn, M; Borradori, L; Yousefi, S; Simon, H-U; Simon, D

2017-07-01

Bullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear. To investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal-epidermal separation (DES). In an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium, DNase or blocking F(ab') 2 fragments to CD16, CD18, CD32 and CD64. Dermal-epidermal separation was assessed by light microscopy studies and quantified using Fiji software. Following activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal-epidermal junction of ex vivo skin. Dermal-epidermal separation was significantly reduced by blocking any of the following: Fcγ receptor binding (P = 0.048), eosinophil adhesion (P = 0.046), reactive oxygen species (ROS) production (P = 0.002), degranulation (P eosinophil extracellular trap (EET) formation (P = 0.048). Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. Dermal-epidermal separation by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Blood Eosinophil and Basophil Values Before and After Surgery for Eosinophilic-type Sinonasal Polyps.

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Brescia, Giuseppe; Parrino, Daniela; Zanotti, Claudia; Tealdo, Giulia; Barion, Umberto; Sfriso, Paolo; Marioni, Gino

2018-01-01

Background Blood eosinophil and basophil levels have recently been considered for the purpose of endotyping chronic rhinosinusitis with nasal polyps (CRSwNP). Histologically, eosinophilic-type CRSwNPs have been associated with high recurrence rates after treatment. Objective The present study was the first to compare blood eosinophil and basophil counts in eosinophilic-type CRSwNP patients before and after endoscopic sinus surgery. Methods The study concerned 79 consecutive patients with histologically confirmed eosinophilic-type CRSwNP treated with endoscopic sinus surgery. Results A significant drop in mean blood eosinophil counts and percentages occurred from before to after endoscopic sinus surgery in the cohort as a whole. Mean blood eosinophil counts and percentages were also reduced after surgery in the subcohorts of CRSwNP patients with (i) asthma, (ii) aspirin-exacerbated respiratory disease (AERD), and (iii) no allergy. Although blood eosinophil and basophil counts correlated directly before and after surgery, a statistical reduction in blood basophil counts and percentages after surgery emerged only in the subcohort of nonallergic CRSwNP patients. Conclusion Endoscopic sinus surgery can clear polyps, remove inflammatory tissue, and reduce inflammatory cytokine levels. Consistently with the biological mechanism described, endoscopic sinus surgery could coincide with a reduction in blood eosinophils in eosinophilic-type CRSwNP.

Impaired CD23 and CD62L expression and tissue inhibitors of metalloproteinases secretion by eosinophils in adults with atopic dermatitis.

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de Oliveira Titz, T; Orfali, R L; de Lollo, C; Dos Santos, V G; da Silva Duarte, A J; Sato, M N; Aoki, V

2016-12-01

Eosinophils are multifunctional, polymorphonuclear leucocytes that secrete proteins within cytoplasmic granules, such as cytokines, chemokines, metalloproteinases (MMPs) and metalloproteinases tissue inhibitors (TIMPs). Although eosinophilia is a hallmark of atopic dermatitis (AD), several functional aspects of eosinophils remain unknown. We aimed to evaluate the phenotype and functional response of eosinophils under staphylococcal enterotoxin B (SEB) and Toll-like receptor (TLR)-2/6 (FSL-1) stimulation in the secretion of CCL5, MMPs and TIMPs in adults with AD. Forty-one adult patients with AD and 45 healthy controls enrolled for the study. Phenotype of eosinophils from granulocytes of peripheral blood was analysed by flow cytometry. We performed evaluation of CCL5 (cytometric bead array), MMP and TIMP (ELISA) secretion, in culture supernatants of purified eosinophils stimulated with SEB or TLR2/6 agonist (FSL-1). We found a higher frequency of LIN1 - CCR3 + eosinophils, and decreased expression of CD23 and CD62L receptors in eosinophils of AD patients. There was no difference in MMP and TIMP serum levels between the evaluated groups. However, we detected decreased basal levels of TIMP-1, TIMP-2 and CCL5 in culture supernatants from purified, unstimulated eosinophils from AD patients. In adults with AD, phenotypical features of eosinophils reveal decreased expression of early activation and L-selectin receptors. Regarding the functional profile of purified eosinophils related to tissue remodelling in atopic dermatitis, innate immune stimulation (TLR2/6 agonist and SEB) did not affect the ratio of MMP/TIMPs secretion in AD. Our findings reinforce the potential breakdown in tissue remodelling process mediated by eosinophils in AD. © 2016 European Academy of Dermatology and Venereology.

Eosinophilic myocarditis due to Churg-Strauss syndrome with markedly elevated eosinophil cationic protein.

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Hara, Tomoya; Yamaguchi, Koji; Iwase, Takashi; Kadota, Muneyuki; Bando, Mika; Ogasawara, Kozue; Bando, Sachiko; Ise, Takayuki; Niki, Toshiyuki; Ueda, Yuka; Tomita, Noriko; Taketani, Yoshio; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Sata, Masataka

2013-01-01

A 67-year-old woman with asthma visited our hospital with increasing dyspnea and new-onset paresthesia and purpura in her legs. Physical examination showed a wheeze, pretibial edema, and surrounding purpura. Chest X-rays showed cardiac decompensation and an electrocardiogram revealed a new ST-T change. Laboratory data showed leukocytosis, hypereosinophilia (10,450/μL), troponin T(+), elevated BNP, and markedly elevated eosinophil cationic protein (ECP) (> 150 ng/mL). Echocardiography revealed diffuse left ventricular hypokinesis (ejection fraction 30%) with increased wall thickness. Coronary angiography was normal. Cardiac magnetic resonance imaging implied diffuse myocardial edema and subendocardial late gadolinium enhancement. Skin biopsy of purpura showed superfi cial perivascular dermatitis with remarkable eosinophilic infiltrations. No evidence of drug allergies, parasitic infection, or myeloproliferative disorder was detected. Based on these findings, a diagnosis of eosinophilic myocarditis due to Churg-Strauss syndrome was considered. She was administered prednisolone at a dose of 1 mg/kg, cyclophosphamide, and diuretics. Several markers of eosinophilic myocarditis and heart failure gradually improved, including ECP. She was discharged 30 days later with no cardiac event. Eosinophilic myocarditis is characterized by predominantly eosinophilic infi ltration. Eosinophilic granule proteins, such as ECP and major basic protein, play important roles in the pathogenesis of eosinophilic myocarditis. We experienced a rare case of eosinophilic myocarditis due to Churg-Strauss syndrome. Markedly elevated ECP played an important role in the early diagnosis and subsequent reduction in ECP served as a marker of monitoring. In an asthmatic patient with dyspnea, hypereosinophilia, and vasculitis, Churg-Strauss syndrome with eosinophilic myocarditis should be considered.

Case report

African Journals Online (AJOL)

abp

2014-03-13

Mar 13, 2014 ... Published in partnership with the African Field Epidemiology Network (AFENET). ... publications have been made on this disease around the world [1]. ... abundant cytoplasm, and eosinophilic granular cells with a round.

Inhibition of NF-κB by a cell permeable form of IκBα induces apoptosis in eosinophils

International Nuclear Information System (INIS)

Fujihara, Satoko; Jaffray, Ellis; Farrow, Stuart N.; Rossi, Adriano G.; Haslett, Christopher; Hay, Ronald T.

2005-01-01

An 11 amino acid HIV-TAT peptide can deliver target proteins into a variety of cells in a receptor-independent manner. To generate a highly specific inhibitor of the transcription factor NF-κB, we have fused the TAT-peptide to a version of IκBα that is resistant to signal-induced degradation. TAT-IκBα(S32A, S36A) inhibited NF-κB-dependent transcription in HeLa and A549 cells by retaining NF-κB p65 in the cytoplasm. Introduction of TAT-IκBα(S32A, S36A) into human eosinophils inhibited the nuclear translocation of NF-κB and induced apoptosis. Thus, continuous NF-κB-dependent transcription is important for eosinophil survival. While eosinophils are normally refractive to standard methods of gene delivery, the ability of TAT fusion proteins to be taken up by these cells should enable a detailed molecular analysis of survival pathways in these cells

Eosinophilic Endotype of Asthma.

Science.gov (United States)

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Primary histiocytic sarcoma arising in the head and neck with predominant spindle cell component

Directory of Open Access Journals (Sweden)

Zhao XF

2007-02-01

Full Text Available Abstract This is the first case report of Histiocytic Sarcoma (HS with predominant spindle cell component occurring in the head and neck region of a 41-year-old man. The tumor was composed of sheets of large round to oval cells with pleomorphic vesicular nuclei, prominent nucleoli and abundant eosinophilic cytoplasm. Multinucleated forms, numerous mitoses, and tumor necrosis were also noted. Sheets, fascicles, and whorls of spindle cells with spindled to ovoid vesicular nuclei, small to medium-sized distinct nucleoli, and eosinophilic cytoplasm were frequently observed. Immunohistochemical staining in the tumor cells was positive for CD163, CD68, lysozyme, CD45, and NSE. Focal expression of CD4 and S-100 was also noted. Electron microscopy demonstrated an abundance of lysosomes in the cytoplasm of tumor cells. Chromosome study revealed a 57–80 hyperdiploid [7]/46, XY [13] karyotype, including 3 to 4 copies of various chromosomes. The immunohistochemical and ultrastructural findings confirmed the diagnosis of HS.

Eosinophilic infiltration in Korea: idiopathic?

Energy Technology Data Exchange (ETDEWEB)

Lim, Jae Hoon; Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2006-03-15

Eosinophilia is defined as the presence of more than 500 eosinophils/{mu}L in the peripheral blood, and may be accompanied by eosinophil infiltration in tissues. Focal eosinophilic infiltration in the lungs and liver is relatively common and is often associated with a parasitic infection, drug hypersensitivity, allergic diseases, collagen vascular diseased, and internal malignancies such as Hodgkin's disease, as well as cancer of the lung, stomach, pancreas or ovary. An eosinophilic abscess refers to a lesion of massive eosinophil infiltration and associated destroyed tissue, and an eosinophilic granuloma refers to a lesion consisting of central necrosis and mixed inflammatory cell infiltrates with numerous eosinophils, a number of neutrophils and lymphocytes, and a palisade of epithelioid histiocytes and/or giant cells.

Eosinophilic infiltration in Korea: idiopathic?

International Nuclear Information System (INIS)

Lim, Jae Hoon; Lee, Kyung Soo

2006-01-01

Eosinophilia is defined as the presence of more than 500 eosinophils/μL in the peripheral blood, and may be accompanied by eosinophil infiltration in tissues. Focal eosinophilic infiltration in the lungs and liver is relatively common and is often associated with a parasitic infection, drug hypersensitivity, allergic diseases, collagen vascular diseased, and internal malignancies such as Hodgkin's disease, as well as cancer of the lung, stomach, pancreas or ovary. An eosinophilic abscess refers to a lesion of massive eosinophil infiltration and associated destroyed tissue, and an eosinophilic granuloma refers to a lesion consisting of central necrosis and mixed inflammatory cell infiltrates with numerous eosinophils, a number of neutrophils and lymphocytes, and a palisade of epithelioid histiocytes and/or giant cells

Eosinophilic cystitis in children

International Nuclear Information System (INIS)

Liu Ming; Zhang Yuzhen; Li Yuhua; Wang Qiuyan; Xie Hua

2006-01-01

Objective: To discuss the clinical manifestations and CT findings of eosinophilic cystitis in children. Methods: Nine cases including Six boys and 3 girls, three to 13 years old, mean age of 8.3- year, have symptoms of hematuria, irritative voiding, dysuria and abdominal pain. The eosinophilic cystitis was pathologically proved in 7 patients and eosinophilic granulomatous cystitis in 2 patients, which based on cystoscopic tissue biopsy or surgery retrospectively. Results: Local thickened bladder walls or nodular and sessile masses along the bladder dome showed in four cases with eosinophilic granulomatous cystitis, and the diffusely irregularly thickened bladder wails showed on CT scans in the rest 5 cases with eosinophilic cystitis. Conclusion: CT findings are helpful to reveal the site, size and other features of eosinophilic cystitis in children. But biopsy of the lesion is necessary to rule out other bladder tumor and selecting the proper management. (authors)

Eosinophilic myositis: an updated review.

Science.gov (United States)

Selva-O'Callaghan, A; Trallero-Araguás, E; Grau, J M

2014-01-01

Eosinophilia-associated myopathies are clinically and pathologically heterogeneous conditions characterized by the presence of peripheral and/or muscle eosinophilia. There are at least three distinct subtypes: focal eosinophilic myositis, eosinophilic polymyositis, and eosinophilic perimyositis. Infiltrating eosinophils are not always identified in conventional muscle histologic examination, but the eosinophil major basic protein, whose extracellular diffusion is considered a hallmark of eosinophilic cytotoxicity, is usually detected by immunostaining in muscle biopsy. Whereas focal eosinophilic myositis seems to be a benign and isolated condition, and perimyositis is usually related with the inflammatory infiltrate due to fasciitis, eosinophilic polymyositis can be associated with muscular dystrophy or be a feature of multiorgan hypereosinophilic syndrome. Muscle biopsy remains the cornerstone for the diagnosis. Parasitic infections, connective tissue disorders, hematologic and non-hematologic malignancies, drugs, and toxic substances are the main etiologic agents of eosinophilia-associated myopathy. However, in some cases, no known etiologic factor is identified, and these are considered idiopathic. Glucocorticoids are the mainstay therapy in idiopathic forms. Imatinib and mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, may be useful in patients with eosinophilic myositis as part of a hypereosinophilic syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

Relationship among antineutrophil cytoplasmic antibody, blood urea nitrogen and complement in patients with eosinophilic granulomatosis polyangiitis (Churg-Strauss syndrome).

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Kawakami, Tamihiro; Kimura, Satoko; Takeuchi, Sora; Soma, Yoshinao

2013-07-01

Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterized by a history of asthma, hypereosinophilia. The prevalence of ANCA in EGPA is less common than in other ANCA-associated vasculitis. Increasing evidence of complement activation in the pathogenesis of ANCA-associated vasculitis has been provided by studies in animal models. We examined EGPA patients with cutaneous manifestations as an initial sign and investigated the correlations among clinical, serological and histopathological findings. We focused on differences among ANCA, blood urea nitrogen and complement levels such as complement 3 (C3), C4 and total complement hemolytic activity (CH50). We retrospectively investigated the records of 22 patients (11 male and 11 female) with EGPA admitted to our hospital from 1997-2012. Ten of the 22 patients (46%) were positive for serum myeloperoxidase (MPO)-ANCA. In contrast, all the patients were negative for serum proteinase 3 ANCA. There was a significantly positive correlation between serum CH50 and C4 levels in patients with EGPA. Serum blood urea nitrogen (BUN) levels differed significantly between MPO-ANCA-positive and -negative patients. Serum CH50 levels were higher in MPO-ANCA-positive patients compared to negative patients. Serum BUN levels were higher in elevated CH50 patients compared to normal and low CH50-negative patients. We propose that positive findings for MPO-ANCA with CH50 high activity may be a risk factor for developing renal insufficiency. Assuming there are correlations between the presence of ANCA and complements, earlier diagnosis based on initial efficacious treatment for EGPA. © 2013 Japanese Dermatological Association.

Autoradiography and density gradient separation of technetium-99m-Exametazime (HMPAO) labelled leucocytes reveals selectivity for eosinophils

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Puncher, M.R.B. [Biological Lab., Univ. of Kent, Canterbury (United Kingdom); Blower, P.J. [Nuclear Medicine Dept., Kent and Canterbury Hospital (United Kingdom)

1994-11-01

Technetium-99m-Exametazime (HMPAO) is widely used for radiolabelling leucocytes for localization of infection. The subcellular distribution of radionuclide in the labelled cells and the distribution of radioactivity among the leucocyte population are incompletely understood. Frozen section autoradiography was used to determine quantitatively the distribution of {sup 99m}Tc in leucocytes labelled with {sup 99m}Tc-Exametazime. Sections of rapidly frozen suspensions of labelled leucocytes in plasma were autoradiographed on Ilford K2 emulsion and stained with haematoxylin and eosin. Neutrophils, eosinophils and mononuclear cells were separated by Percoll density gradient centrifugation. Cell nuclei were isolated by a rapid cell-breakage and fractionation method. In a typical experiment mean grain densities [grains/100 {mu}m{sup 2} (ESD)] over cells were: eosinophils 31.2 (18.4), neutrophils 3.5 (3.5), mononuclear cells 4.2 (5.1). Mean grain numbers per cell (ESD) were: eosinophils 13 (6.8), neutrophils 1.3 (1.3), mononuclear cells 1.1 (1.3). These findings were confirmed by separation of labelled leucocytes on discontinuous density gradients. In four separation experiments, the mean activity-per-cell ratio for eosinophils to neutrophils was 10.1 (4.8):1, and for eosinophils to mononuclear cells, 14.1 (6.7):1. The subcellular distribution of the label was investigated using image analysis of autoradiographs and cell fractionation. This revealed no selectivity for nuclear or extranuclear compartments. It may be concluded that {sup 99m}Tc-Exametazime has strong selectivity for eosinophils over other leucocytes but no selectivity for nuclear/cytoplasmic compartments. (orig.)

Eosinophilic Lung Disorders

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... problems characterized by having an increased number of eosinophils (white blood cells) in the lungs. These white ... category of pneumonias that feature increased numbers of eosinophils in the lung tissue. Pneumonia is an inflammatory ...

Human Eosinophils Express Functional CCR7

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Ueki, Shigeharu; Estanislau, Jessica; Weller, Peter F.

2013-01-01

Human eosinophils display directed chemotactic activity toward an array of soluble chemokines. Eosinophils have been observed to migrate to draining lymph nodes in experimental models of allergic inflammation, yet it is unknown whether eosinophils express CCR7, a key chemokine receptor in coordinating leukocyte trafficking to lymph nodes. The purpose of this study is to demonstrate expression of CCR7 by human eosinophils and functional responses to CCL19 and CCL21, the known ligands of CCR7. Human eosinophils were purified by negative selection from healthy donors. CCR7 expression of freshly purified, unstimulated eosinophils and of IL-5–primed eosinophils was determined by flow cytometry and Western blot. Chemotaxis to CCL19 and CCL21 was measured in transwell assays. Shape changes to CCL19 and CCL21 were analyzed by flow cytometry and microscopy. Calcium fluxes of fluo-4 AM–loaded eosinophils were recorded by flow cytometry after chemokine stimulation. ERK phosphorylation of CCL19- and CCL21-stimulated eosinophils was measured by Western blot and Luminex assay. Human eosinophils expressed CCR7 as demonstrated by flow cytometry and Western blots. Eosinophils exhibited detectable cell surface expression of CCR7. IL-5–primed eosinophils exhibited chemotaxis toward CCL19 and CCL21 in a dose-dependent fashion. Upon stimulation with CCL19 or CCL21, IL-5–primed eosinophils demonstrated dose-dependent shape changes with polarization of F-actin and exhibited calcium influxes. Finally, primed eosinophils stimulated with CCL19 or CCL21 exhibited increased phosphorylation of ERK in response to both CCR7 ligands. We demonstrate that human eosinophils express CCR7 and have multipotent responses to the known ligands of CCR7. PMID:23449735

External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma.

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Wagener, A H; de Nijs, S B; Lutter, R; Sousa, A R; Weersink, E J M; Bel, E H; Sterk, P J

2015-02-01

Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE(NO) show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic inflammation. Quantifying the mutual relationships of blood eosinophils, FE(NO), and serum periostin with sputum eosinophils by external validation in two independent cohorts across various severities of asthma. The first cohort consisted of 110 patients with mild to moderate asthma (external validation cohort). The replication cohort consisted of 37 patients with moderate to severe asthma. Both cohorts were evaluated cross-sectionally. Sputum was induced for the assessment of eosinophils. In parallel, blood eosinophil counts, serum periostin concentrations and FENO were assessed. The diagnostic accuracy of these markers to identify eosinophilic asthma (sputum eosinophils ≥3%) was calculated using receiver operating characteristics area under the curve (ROC AUC). In the external validation cohort, ROC AUC for blood eosinophils was 89% (peosinophilic from non-eosinophilic airway inflammation (ROC AUC=55%, p=0.44). When combining these three variables, no improvement was seen. The diagnostic value of blood eosinophils was confirmed in the replication cohort (ROC AUC 85%, peosinophils had the highest accuracy in the identification of sputum eosinophilia in asthma. The use of blood eosinophils can facilitate individualised treatment and management of asthma. NTR1846 and NTR2364. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical features of so-called eosinophilic rhinosinusitis. With a view to screening for eosinophilic rhinosinusitis

International Nuclear Information System (INIS)

Sakuma, Yasunori; Ishitoya, Junichi; Kimura, Machiko; Hirose, Shouji; Takahashi, Masahiro; Tsukuda, Mamoru

2006-01-01

The concept of so-called eosinophilic sinusitis has recently come to be understood, but since the definition and the diagnostic criteria for this intractable form of sinusitis are unclear, we reviewed the clinical features of 104 patients (16 with eosinophilic sinusitis and 88 with non-eosionphilic sinusitis) who underwent endonasal sinus surgery in our department. So-called eosinophilic sinusitis was usually accompanied by severe bronchial asthma, and the characteristic clinical findings of so-called eosinophilic sinusitis were an increase in peripheral blood eosinophil count, a paranasal sinus shadow in computed tomograms (CT score), and a high ethmoid sinus/maxillary sinus score ratio (E/M ratio) in our study. We determined the cutoff value to review sensitivity, specificity and correct diagnosis rate in screening for eosinophilic sinusitis. When we judged using three cutoff values, a peripheral blood eosinophil count≥500/μ1, CT score≥13 and E/M ratio≥1, a sensitivity of 69%, specificity of 97% and correct diagnosis rate of 81%. On the other hand, when we judged using two cutoff value, peripheral blood eosinophil count≥500/μ1 and E/M ratio≥1, sensitivity of 75%, specificity of 94% and correct diagnosis rate of 88%. Because all three studies can be performed in outpatient clinics, we concluded that they are useful as a method of screening for so-called eosinophilic sinusitis without the need for histological examinations for eosinophil infiltration of nasal polyps in biopsy specimens. (author)

Eosinophils in lichen sclerosus et atrophicus.

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Keith, Phillip J; Wolz, Michael M; Peters, Margot S

2015-10-01

The classic histopathologic features of lichen sclerosus et atrophicus (LS) include lymphoplasmacytic inflammation below a zone of dermal edema and sclerosis. The presence of eosinophils in LS has received little attention, but the finding of tissue eosinophils, particularly eosinophilic spongiosis in LS, has been suggested as a marker for the coexistence of autoimmune bullous disease or allergic contact dermatitis (or both). We sought to determine whether the histopathologic presence of dermal eosinophils or eosinophilic spongiosis (or both) in biopsies from patients with LS is associated with autoimmune bullous disease, autoimmune connective tissue disease or allergic contact dermatitis. A retrospective review of the histopathology and medical records of 235 patients with LS who were evaluated from June 1992 to June 2012 was performed. Sixty-nine patients (29%) had eosinophils on histopathology. Among patients with associated diseases, a statistically significant association between the eosinophil cohort and the cohort without eosinophils was not detected. The importance of eosinophils is uncertain, but our data suggest that the finding of tissue eosinophils alone is not sufficient to prompt an extensive workup for additional diagnoses. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome and pulmonary thromboembolism: an overlooked concomitance

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Vilma Takayasu

2013-06-01

Full Text Available The Eosinophilic Granulomatosis with Polyangiitis (formerly Churg- Strauss Syndrome (EGPA is a systemic inflammatory disease characterized by the presence of rhinitis, asthma, peripheral eosinophilia, and vasculitis—the latter being characteristic of the late stage of the disease. After several years from the onset of the disease, small- and medium-sized vessel vasculitis ensues, undertaking various organs and systems. Upper and lower airways, skin, nervous system, gastrointestinal tract, heart, and kidneys are the most commonly involved organs. It is believed that tissue injury is the result of processes mediated by antineutrophil cytoplasmic antibody (ANCA, or toxic mediators released by eosinophils. Although it is classified as ANCA-associated vasculitis, these autoantibodies are present in only 40% of cases. The authors report the case of a patient with EGPA, who had a history of asthma, peripheral and central neuropathy, palpable purpura, gastrointestinal micro perforation, peripheral eosinophilia, and the presence of myeloperoxidase-antineutrophil cytoplasmic antibody. Inflammatory parameters improved after the initiation of treatment, but 1 month after hospital discharge the patient developed symptoms compatible with pulmonary embolism and died. Thrombophilia that occurs in EGPA is due to the interaction between the inflammatory response and eosinophilia with the clotting system resulting in a pro-thrombotic state. Although not yet well-determined, the authors call attention to the possibility of the impact of thromboembolic events on the prognosis of patients with EGPA. In addition to the adequate immunosuppressive treatment, prophylaxis and treatment for thrombosis should never be overlooked.

Eosinophilic panniculitis.

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Samlaska, C P; de Lorimier, A J; Heldman, L S

1995-03-01

Eosinophillic panniculitis is a poorly defined entity with variable clinical features. We report a case of rapidly enlarging, asymptomatic subcutaneous scalp nodules in a 6-year-old black boy with atopic dermatitis. The nodules resolved spontaneously over two to three days. Biopsy specimens were remarkable for eosinophilic panniculitis without evidence of epidermal change or vasculitis. We believe that this is the youngest reported patient with this disorder.

Eosinophils, probiotics, and the microbiome.

Science.gov (United States)

Rosenberg, Helene F; Masterson, Joanne C; Furuta, Glenn T

2016-11-01

There is currently substantial interest in the therapeutic properties of probiotic microorganisms as recent research suggests that oral administration of specific bacterial strains may reduce inflammation and alter the nature of endogenous microflora in the gastrointestinal tract. Eosinophils are multifunctional tissue leukocytes, prominent among the resident cells of the gastrointestinal mucosa that promote local immunity. Recent studies with genetically altered mice indicate that eosinophils not only participate in maintaining gut homeostasis, but that the absence of eosinophils may have significant impact on the nature of the endogenous gut microflora and responses to gut pathogens, notably Clostridium difficile Furthermore, in human subjects, there is an intriguing relationship between eosinophils, allergic inflammation, and the nature of the lung microflora, notably a distinct association between eosinophil infiltration and detection of bacteria of the phylum Actinobacteria. Among topics for future research, it will be important to determine whether homeostatic mechanisms involve direct interactions between eosinophils and bacteria or whether they involve primarily eosinophil-mediated responses to cytokine signaling in the local microenvironment. Likewise, although is it clear that eosinophils can and do interact with bacteria in vivo, their ability to discern between pathogenic and probiotic species in various settings remains to be explored. © Society for Leukocyte Biology.

External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma

NARCIS (Netherlands)

Wagener, A. H.; de Nijs, S. B.; Lutter, R.; Sousa, A. R.; Weersink, E. J. M.; Bel, E. H.; Sterk, P. J.

2015-01-01

Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE(NO) show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic

Expression of cysLT1 and cysLT2 Receptor in Chronic Hyperplastic Eosinophilic Sinusitis

International Nuclear Information System (INIS)

Ouyang, Yuhui; Kamijo, Atsushi; Murata, Shin-ichi; Okamoto, Atsushi; Endo, Shuichiro; Katoh, Ryohei; Masuyama, Keisuke

2009-01-01

Elevated production of cysteinyl leukotrienes (cysLTs) from sinus tissues and abundant sinus eosinophils are characteristic features of chronic hyperplastic eosinophilic sinusitis (CHS). CysLTs exert their action through G-protein-coupled receptors named cysLTs receptor type I (cysLT1R) and type II (cysLT2R). These expressions of cysLT receptors in the sinus mucosa have yet to be clarified and the relationship between eosinophilia and the expression of these receptors remains obscure. We compared the expressions of cysLT1R and cysLT2R in the sinus mucosa in patients with CHS, non-eosinophilic chronic sinusitis (NECS), and control sinus tissues; and analyzed the correlation between the expression of CysLTRs and the presence of sinus eosinophils by immunohistochemistry and real-time PCR. A significantly higher percentage of eosinophils expressing cysLT2R protein was observed in patients with CHS compared with NECS and controls. In addition, cysLT2R mRNA expression in CHS was significantly higher than in NECS and controls. Furthermore, a positive correlation was observed between cysLT2R mRNA expression and the number of infiltrated eosinophils. In contrast, the cysLT1R mRNA expression did not differ significantly among these groups. The effect of cysLTs on sinus eosinophils may be mediated through the cysLT2R in patients with CHS. These results may suggest the therapeutic benefit of cysLT2R antagonists in CHS

Acute eosinophilic pneumonia: a case report

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Jung, Gyoo; Sik; Oh, Kyung Seung; Kim, Jong Min; Huh, Jin Do; Joh, Young Duk; Jang, Tae Won; Jung, Man Hong [Kosin Medical College, Busan (Korea, Republic of)

1995-10-15

Acute eosinophilic pneumonia is one of a recently described idiopathic eosinophilic lung disease, which differs from chronic eosinophilic pneumonia. Patients with acute eosinophilic pneumonia develop acute onset of dyspnea, hypoxemia, diffuse pulmonary infiltrates and pleural effusion on chest radiograph, and show an increase in number of eosinophils in bronchoalveolar lavage fluid or lung biopsy specimen. Prompt and complete response to corticosteroid therapy without any recurrence is characteristically seen in patient with this disease. Although the etiology of acute eosinophilic pneumonia is not known, it has been suggested to be related to a hypersensitivity phenomenon to an unidentified inhaled antigen. We report four cases of acute eosinophilic pneumonia presented with acute onset of dyspnea, diffuse pulmonary infiltrates on chest radiograph, and eosinophilia in bronchoalveolar lavage fluid in previously healthy adults.

Acute eosinophilic pneumonia: a case report

International Nuclear Information System (INIS)

Jung, Gyoo; Sik; Oh, Kyung Seung; Kim, Jong Min; Huh, Jin Do; Joh, Young Duk; Jang, Tae Won; Jung, Man Hong

1995-01-01

Acute eosinophilic pneumonia is one of a recently described idiopathic eosinophilic lung disease, which differs from chronic eosinophilic pneumonia. Patients with acute eosinophilic pneumonia develop acute onset of dyspnea, hypoxemia, diffuse pulmonary infiltrates and pleural effusion on chest radiograph, and show an increase in number of eosinophils in bronchoalveolar lavage fluid or lung biopsy specimen. Prompt and complete response to corticosteroid therapy without any recurrence is characteristically seen in patient with this disease. Although the etiology of acute eosinophilic pneumonia is not known, it has been suggested to be related to a hypersensitivity phenomenon to an unidentified inhaled antigen. We report four cases of acute eosinophilic pneumonia presented with acute onset of dyspnea, diffuse pulmonary infiltrates on chest radiograph, and eosinophilia in bronchoalveolar lavage fluid in previously healthy adults

The Regulatory Function of Eosinophils.

Science.gov (United States)

Wen, Ting; Rothenberg, Marc E

2016-10-01

Eosinophils are a minority circulating granulocyte classically viewed as being involved in host defense against parasites and promoting allergic reactions. However, a series of new regulatory functions for these cells have been identified in the past decade. During homeostasis, eosinophils develop in the bone marrow and migrate from the blood into target tissues following an eotaxin gradient, with interleukin-5 being a key cytokine for eosinophil proliferation, survival, and priming. In multiple target tissues, eosinophils actively regulate a variety of immune functions through their vast arsenal of granule products and cytokines, as well as direct cellular interaction with cells in proximity. The immunologic regulation of eosinophils extends from innate immunity to adaptive immunity and also involves non-immune cells. Herein, we summarize recent findings regarding novel roles of murine and human eosinophils, focusing on interactions with other hematopoietic cells. We also review new experimental tools available and remaining questions to uncover a greater understanding of this enigmatic cell.

Radioimmunoassay of human eosinophil cationic protein

International Nuclear Information System (INIS)

Venge, P.; Roxin, L.E.; Olsson, I.

1977-01-01

A radioimmunosorbent assay has been developed which allows the detection in serum of a cationic protein derived from eosinophil granulocytes. In 34 healthy individuals the mean level was 31 μg/l. with a range of 5 to 55 μg/l. The serum concentration of 'eosinophil' cationic protein was correlated (P<0.001) to the number of eosinophil granulocytes in peripheral blood. Quantitiation of 'eosinophil' cationic protein in serum might be useful in the study of eosinophil granulocyte turnover and function in vivo. (author)

Eosinophilic Esophagitis (EoE)

Science.gov (United States)

... specific responses in allergy? » Dietary Therapy and Nutrition Management of Eosinophilic Esophagitis: A Work Group Report of the American Academy of Allergy, Asthma, and Immunology » Eosinophilic esophagitis can ...

Radiographic and pathologic observations of eosinophilic gastroenteritis

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Jung, Lae Won [Busan Nationa University College of Medicine, Busan (Korea, Republic of); Hong, Sook Hee; Lee, Jung Dal [Busan Gospel Hospital, Busan (Korea, Republic of)

1974-10-15

This report presents two cases with eosinophilic gastroenteritis in detail. The radiographic and pathologic features of eosinophilic gastroenteritis are summarized with emphasis on the differential diagnostic features. Radiographic eosinophilic gastritis should be differentiated from gastric carcinoma and lymphoma, and eosinophilic enteritis from intestinal tuberculosis and intussusception of the small bowel in Korea where these entities are prevent. Eosinophilic gastroenteritis is pathologically characterized by diffuse infiltration of the submucosa and muscle coats with eosinophilic in conjunction with hypertrophy of individual muscle fibers. This leads to thickening of the gastrointestinal wall resulting in narrowing and obstruction of the lumen. Eosinophilic venulitis is another characteristic feature which is helpful for differentiation this entity from a parasitic infection.

Radiographic and pathologic observations of eosinophilic gastroenteritis

International Nuclear Information System (INIS)

Jung, Lae Won; Hong, Sook Hee; Lee, Jung Dal

1974-01-01

This report presents two cases with eosinophilic gastroenteritis in detail. The radiographic and pathologic features of eosinophilic gastroenteritis are summarized with emphasis on the differential diagnostic features. Radiographic eosinophilic gastritis should be differentiated from gastric carcinoma and lymphoma, and eosinophilic enteritis from intestinal tuberculosis and intussusception of the small bowel in Korea where these entities are prevent. Eosinophilic gastroenteritis is pathologically characterized by diffuse infiltration of the submucosa and muscle coats with eosinophilic in conjunction with hypertrophy of individual muscle fibers. This leads to thickening of the gastrointestinal wall resulting in narrowing and obstruction of the lumen. Eosinophilic venulitis is another characteristic feature which is helpful for differentiation this entity from a parasitic infection

Differentiation of eosinophilic leukemia EoL-1 cells into eosinophils induced by histone deacetylase inhibitors.

Science.gov (United States)

Ishihara, Kenji; Takahashi, Aki; Kaneko, Motoko; Sugeno, Hiroki; Hirasawa, Noriyasu; Hong, JangJa; Zee, OkPyo; Ohuchi, Kazuo

2007-03-06

EoL-1 cells differentiate into eosinophils in the presence of n-butyrate, but the mechanism has remained to be elucidated. Because n-butyrate can inhibit histone deacetylases, we hypothesized that the inhibition of histone deacetylases induces the differentiation of EoL-1 cells into eosinophils. In this study, using n-butyrate and two other histone deacetylase inhibitors, apicidin and trichostatin A, we have analyzed the relationship between the inhibition of histone deacetylases and the differentiation into eosinophils in EoL-1 cells. It was demonstrated that apicidin and n-butyrate induced a continuous acetylation of histones H4 and H3, inhibited the proliferation of EoL-1 cells without attenuating the level of FIP1L1-PDGFRA mRNA, and induced the expression of markers for mature eosinophils such as integrin beta7, CCR1, and CCR3 on EoL-1 cells, while trichostatin A evoked a transient acetylation of histones and induced no differentiation into eosinophils. These findings suggest that the continuous inhibition of histone deacetylases in EoL-1 cells induces the differentiation into mature eosinophils.

Comparison of Toxocariasis Frequency in Hyper- eosinophilic and Non-Eosinophilic Individuals Referred to Abadan Health Centers

Directory of Open Access Journals (Sweden)

Sharif Maraghi

2014-07-01

Full Text Available Background: Toxocariasis is a zoonotic helminthic infection of humans and animals caused by the larvae of intestinal parasites of dogs and cats (Toxocara canis and Toxocara cati, respectively. These nematodes develop in to their adult stage in the intestines of cats and dogs. Three clinical entities have been recognized in humans; visceral larva migrans, ocular larva migrans and covert toxocariasis. Eosinophilia is a common finding in infected patients Objectives: In this study the frequency of toxocariasis in eosinophilic and non-eosinophilic individuals referred to the laboratory of Abadan health centers was compared. Materials and Methods: Serum samples were collected from individuals attending the laboratory of health centers for any medical problem and were tested for complet blood count (CBC. The samples of patients were divided in to two groups, those with more than 10% peripheral eosinophils, as the eosinophilic group (n = 54 and those with normal eosinophils (0-3% as the non-eosinophilic group (n = 54. Samples were examined for anti-oxocara IgG by the enzyme linked immunosorbent assay (ELISA and confirmed western blotting. Results: Anti-oxocara IgG was detected in the sera of six (11.11% cases from the eosinophilic group and two (3.7% of the non-eosinophilic group by the ELISA method, but all had negative results for the western blot analysis. Conclusions: The results of this study indicated that the eosinophilic individuals might beexposed to other helminthic infections or allergic agents. Further studies are required with more samples with different ages and occupations.

Humoral immunity provides resident intestinal eosinophils access to luminal antigen via eosinophil-expressed low affinity Fc gamma receptors

Science.gov (United States)

Smith, Kalmia M.; Rahman, Raiann S.; Spencer, Lisa A.

2016-01-01

Eosinophils are native to the healthy gastrointestinal tract, and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g. food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct antigen engagement elicits eosinophil effector functions including degranulation and antigen presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food antigens by a columnar epithelium might similarly engage food antigens. Using an intestinal ligated loop model in mice, here we determined that resident intestinal eosinophils acquire antigen from the lumen of antigen-sensitized but not naïve mice in vivo. Antigen acquisition was immunoglobulin-dependent; intestinal eosinophils were unable to acquire antigen in sensitized immunoglobulin-deficient mice, and passive immunization with immune serum or antigen-specific IgG was sufficient to enable intestinal eosinophils in otherwise naïve mice to acquire antigen in vivo. Intestinal eosinophils expressed low affinity IgG receptors, and the activating receptor FcγRIII was necessary for immunoglobulin-mediated acquisition of antigens by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food antigens in sensitized mice via FcγRIII antigen focusing, and may therefore participate in antigen-driven secondary immune responses to oral antigens. PMID:27683752

Humoral Immunity Provides Resident Intestinal Eosinophils Access to Luminal Antigen via Eosinophil-Expressed Low-Affinity Fcγ Receptors.

Science.gov (United States)

Smith, Kalmia M; Rahman, Raiann S; Spencer, Lisa A

2016-11-01

Eosinophils are native to the healthy gastrointestinal tract and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g., food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct Ag engagement elicits eosinophil effector functions, including degranulation and Ag presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food Ags by a columnar epithelium might similarly engage food Ags. Using an intestinal ligated loop model in mice, in this study we determined that resident intestinal eosinophils acquire Ag from the lumen of Ag-sensitized but not naive mice in vivo. Ag acquisition was Ig-dependent; intestinal eosinophils were unable to acquire Ag in sensitized Ig-deficient mice, and passive immunization with immune serum or Ag-specific IgG was sufficient to enable intestinal eosinophils in otherwise naive mice to acquire Ag in vivo. Intestinal eosinophils expressed low-affinity IgG receptors, and the activating receptor FcγRIII was necessary for Ig-mediated acquisition of Ags by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food Ags in sensitized mice via FcγRIII Ag focusing and that they may therefore participate in Ag-driven secondary immune responses to oral Ags. Copyright © 2016 by The American Association of Immunologists, Inc.

Cytoplasmic assembly of snRNP particles from stored proteins and newly transcribed snRNA's in L929 mouse fibroblasts

International Nuclear Information System (INIS)

Sauterer, R.A.; Feeney, R.J.; Zieve, G.W.

1988-01-01

Newly synthesized snRNAs appear transiently in the cytoplasm where they assemble into ribonucleoprotein particles, the snRNP particles, before returning permanently to the interphase nucleus. In this report, bona fide cytoplasmic fractions, prepared by cell enucleation, are used for a quantitative analysis of snRNP assembly in growing mouse fibroblasts. The half-lives and abundances of the snRNP precursors in the cytoplasm and the rates of snRNP assembly are calculated in L929 cells. With the exception of U6, the major snRNAs are stable RNA species; U1 is almost totally stable while U2 has a half-life of about two cell cycles. In contrast, the majority of newly synthesized U6 decays with a half-life of about 15 h. The relative abundances of the newly synthesized snRNA species U1, U2, U3, U4 and U6 in the cytoplasm are determined by Northern hybridization using cloned probes and are approximately 2% of their nuclear abundance. The half-lives of the two major snRNA precursors in the cytoplasm (U1 and U2) are approximately 20 min as determined by labeling to steady state. The relative abundance of the snRNP B protein in the cytoplasm is determined by Western blotting with the Sm class of autoantibodies and is approximately 25% of the nuclear abundance. Kinetic studies, using the Sm antiserum to immunoprecipitate the methionine-labeled snRNP proteins, suggest that the B protein has a half-life of 90 to 120 min in the cytoplasm. These data are discussed and suggest that there is a large pool of more stable snRNP proteins in the cytoplasm available for assembly with the less abundant but more rapidly turning-over snRNAs

Eosinophils in vasculitis: characteristics and roles in pathogenesis

Science.gov (United States)

Khoury, Paneez; Grayson, Peter C.; Klion, Amy D.

2016-01-01

Eosinophils are multifunctional granular leukocytes that are implicated in the pathogenesis of a wide variety of disorders, including asthma, helminth infection, and rare hypereosinophilic syndromes. Although peripheral and tissue eosinophilia can be a feature of many types of small-vessel and medium-vessel vasculitis, the role of eosinophils has been best studied in eosinophilic granulomatosis with polyangiitis (EGPA), where eosinophils are a characteristic finding in all three clinical stages of the disorder. Whereas numerous studies have demonstrated an association between the presence of eosinophils and markers of eosinophil activation in the blood and tissues of patients with EGPA, the precise role of eosinophils in disease pathogenesis has been difficult to ascertain owing to the complexity of the disease process. In this regard, results of clinical trials using novel agents that specifically target eosinophils are providing the first direct evidence of a central role of eosinophils in EGPA. This Review focuses on the aspects of eosinophil biology most relevant to the pathogenesis of vasculitis and provides an update of current knowledge regarding the role of eosinophils in EGPA and other vasculitides. PMID:25003763

Activation states of blood eosinophils in asthma

Science.gov (United States)

Johansson, Mats W.

2014-01-01

Asthma is characterized by airway inflammation rich in eosinophils. Airway eosinophilia is associated with exacerbations and has been suggested to play a role in airway remodeling. Recruitment of eosinophils from the circulation requires that blood eosinophils become activated, leading to their arrest on the endothelium and extravasation. Circulating eosinophils can be envisioned as potentially being in different activation states, including non-activated, pre-activated or “primed”, or fully activated. In addition, the circulation can potentially be deficient of pre-activated or activated eosinophils, because such cells have marginated on activated endothelium or extravasated into the tissue. A number of eosinophil-surface proteins, including CD69, L-selectin, intercellular adhesion molecule-1 (ICAM-1, CD54), CD44, P-selectin glycoprotein ligand-1 (PSGL-1, CD162), cytokine receptors, Fc receptors, integrins including αM integrin (CD11b), and activated conformations of Fc receptors and integrins have been proposed to report cell activation. Variation in eosinophil activation states may be associated with asthma activity. Eosinophil-surface proteins proposed to be activation markers, with a particular focus on integrins, and evidence for associations between activation states of blood eosinophils and features of asthma are reviewed here. Partial activation of β1 and β2 integrins on blood eosinophils, reported by monoclonal antibodies (mAb) N29 and KIM-127, is associated with impaired pulmonary function and airway eosinophilia, respectively, in non-severe asthma. The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre-activated cells, in severe disease. PMID:24552191

Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma

NARCIS (Netherlands)

Meijer, RJ; Postma, DS; Kauffman, HF; Arends, LR; Koeter, GH; Kerstjens, HAM

Background There is a large variability in clinical response to corticosteroid treatment in patients with asthma. Several markers of inflammation like eosinophils and eosinophil cationic protein (ECP), as well as exhaled nitric oxide (NO), are good candidates to predict clinical response. Aim We

[Antineutrophil cytoplasmic antibodies associated with infective endocarditis: Literature review].

Science.gov (United States)

Langlois, V; Marie, I

2017-07-01

Antineutrophil cytoplasmic antibodies (ANCA) associated with infective endocarditis are a rare disorder. The condition can mimic primary systemic vasculitis (i.e. granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis). Thus, a wrong diagnosis of valvular involvement related to primary systemic vasculitis can be made in patients exhibiting ANCA associated with infective endocarditis. Because treatment of both conditions is different, this wrong diagnosis will lead to dramatic consequences in these latter patients. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of ANCA associated with infective endocarditis. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Production of monoclonal antibodies reactive with ovine eosinophils

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Meeusen Els NT

2007-09-01

Full Text Available Abstract Background There is strong evidence implicating eosinophils in host defence against parasites as well as allergic disease pathologies. However, a lack of reagents such as monoclonal antibodies (mAbs specific for eosinophils has made it difficult to confirm the functional role of eosinophils in such disease conditions. Using an established mammary model of allergic inflammation in sheep, large numbers of inflammatory cells enriched for eosinophils were collected from parasite-stimulated mammary glands and used for the generation of mAbs against ovine eosinophils. Results A panel of mAbs was raised against ovine eosinophils of which two were shown to be highly specific for eosinophils. The reactivity of mAbs 3.252 and 1.2 identified eosinophils from various cell and tissue preparations with no detectable reactivity on cells of myeloid or lymphoid lineage, tissue mast cells, dendritic cells, epithelial cells or other connective tissues. Two other mAbs generated in this study (mAbs 4.4 and 4.10 were found to have reactivity for both eosinophils and neutrophils. Conclusion This study describes the production of new reagents to identify eosinophils (as well as granulocytes in sheep that will be useful in studying the role of eosinophils in disease pathologies in parasite and allergy models.

Xenopus egg cytoplasm with intact actin.

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Field, Christine M; Nguyen, Phuong A; Ishihara, Keisuke; Groen, Aaron C; Mitchison, Timothy J

2014-01-01

We report optimized methods for preparing Xenopus egg extracts without cytochalasin D, that we term "actin-intact egg extract." These are undiluted egg cytoplasm that contains abundant organelles, and glycogen which supplies energy, and represents the least perturbed cell-free cytoplasm preparation we know of. We used this system to probe cell cycle regulation of actin and myosin-II dynamics (Field et al., 2011), and to reconstitute the large, interphase asters that organize early Xenopus embryos (Mitchison et al., 2012; Wühr, Tan, Parker, Detrich, & Mitchison, 2010). Actin-intact Xenopus egg extracts are useful for analysis of actin dynamics, and interaction of actin with other cytoplasmic systems, in a cell-free system that closely mimics egg physiology, and more generally for probing the biochemistry and biophysics of the egg, zygote, and early embryo. Detailed protocols are provided along with assays used to check cell cycle state and tips for handling and storing undiluted egg extracts. © 2014 Elsevier Inc. All rights reserved.

Eosinophils: The unsung heroes in cancer?

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Varricchi, Gilda; Galdiero, Maria Rosaria; Loffredo, Stefania; Lucarini, Valeria; Marone, Giancarlo; Mattei, Fabrizio; Marone, Gianni; Schiavoni, Giovanna

2018-01-01

Prolonged low-grade inflammation or smoldering inflammation is a hallmark of a cancer. Eosinophils are components of the immune microenvironment that modulates tumor initiation and progression. Although canonically associated with a detrimental role in allergic disorders, these cells can induce a protective immune response against helminthes, viral and bacterial pathogens. Eosinophils are a source of anti-tumorigenic (e.g., TNF-α, granzyme, cationic proteins, and IL-18) and protumorigenic molecules (e.g., pro-angiogenic factors) depending on the milieu. In several neoplasias (e.g., melanoma, gastric, colorectal, oral and prostate cancer) eosinophils play an anti-tumorigenic role, in others (e.g., Hodgkin's lymphoma, cervical carcinoma) have been linked to poor prognosis, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of eosinophils and their mediators could be cancer-dependent. The microlocalization (e.g., peritumoral vs intratumoral) of eosinophils could be another important aspect in the initiation/progression of solid and hematological tumors. Increasing evidence in experimental models indicates that activation/recruitment of eosinophils could represent a new therapeutic strategy for certain tumors (e.g., melanoma). Many unanswered questions should be addressed before we understand whether eosinophils are an ally, adversary or neutral bystanders in different types of human cancers.

Cisplatin-Induced Eosinophilic Pneumonia

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Hideharu Ideguchi

2014-01-01

Full Text Available A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.

Eosinophils mediate protective immunity against secondary nematode infection.

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Huang, Lu; Gebreselassie, Nebiat G; Gagliardo, Lucille F; Ruyechan, Maura C; Luber, Kierstin L; Lee, Nancy A; Lee, James J; Appleton, Judith A

2015-01-01

Eosinophils are versatile cells that regulate innate and adaptive immunity, influence metabolism and tissue repair, and contribute to allergic lung disease. Within the context of immunity to parasitic worm infections, eosinophils are prominent yet highly varied in function. We have shown previously that when mice undergo primary infection with the parasitic nematode Trichinella spiralis, eosinophils play an important immune regulatory role that promotes larval growth and survival in skeletal muscle. In this study, we aimed to address the function of eosinophils in secondary infection with T. spiralis. By infecting eosinophil-ablated mice, we found that eosinophils are dispensable for immunity that clears adult worms or controls fecundity in secondary infection. In contrast, eosinophil ablation had a pronounced effect on secondary infection of skeletal muscle by migratory newborn larvae. Restoring eosinophils to previously infected, ablated mice caused them to limit muscle larvae burdens. Passive immunization of naive, ablated mice with sera or Ig from infected donors, together with transfer of eosinophils, served to limit the number of newborn larvae that migrated in tissue and colonized skeletal muscle. Results from these in vivo studies are consistent with earlier findings that eosinophils bind to larvae in the presence of Abs in vitro. Although our previous findings showed that eosinophils protect the parasite in primary infection, these new data show that eosinophils protect the host in secondary infection. Copyright © 2014 by The American Association of Immunologists, Inc.

Peritumoral eosinophils predict recurrence in colorectal cancer.

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Harbaum, Lars; Pollheimer, Marion J; Kornprat, Peter; Lindtner, Richard A; Bokemeyer, Carsten; Langner, Cord

2015-03-01

In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; Peosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58-0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52-0.93; P=0.01)-independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients independent of the overall tumor-associated inflammatory response. Evaluation of peritumoral eosinophils represents a promising

Regulatory Eosinophils Suppress T Cells Partly through Galectin-10.

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Lingblom, Christine; Andersson, Jennie; Andersson, Kerstin; Wennerås, Christine

2017-06-15

Eosinophils have the capacity to regulate the function of T cell subsets. Our aim was to test the hypothesis of the existence of a regulatory subset of eosinophils. Human eosinophils were incubated with T cells that were stimulated with allogeneic leukocytes or CD3/CD28 cross-linking. After 2 d of coculture, 11% of the eosinophils gained CD16 expression. A CD16 hi subset of eosinophils, encompassing 1-5% of all eosinophils, was also identified in the blood of healthy subjects. FACS sorting showed that these CD16 hi eosinophils were significantly stronger suppressors of T cell proliferation than were conventional CD16 neg eosinophils. Human eosinophils contain stores of the immunoregulatory protein galectin-10. We found that Ab-mediated neutralization of galectin-10 partially abrogated the suppressive function of the eosinophils. Moreover, recombinant galectin-10 by itself was able to suppress T cell proliferation. Finally, we detected galectin-10-containing immune synapses between eosinophils and lymphocytes. To conclude, we describe a subset of suppressive eosinophils expressing CD16 that may escape detection because CD16-based negative selection is the standard procedure for the isolation of human eosinophils. Moreover, we show that galectin-10 functions as a T cell-suppressive molecule in eosinophils. Copyright © 2017 by The American Association of Immunologists, Inc.

Eosinophilic Pancreatitis: A Rare Cause of Recurrent Acute Pancreatitis

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Jennifer Reppucci

2017-03-01

Full Text Available Eosinophilic pancreatitis is a rare form of recurrent acute pancreatitis that demonstrates distinct histologic features, including diffuse, periductal, acinar, and septal inflammatory infiltrates comprised of a pure or predominant population of eosinophils, eosinophilic phlebitis and arteritis, and localized eosinophilic infiltrates with pseudocyst formation. It is associated with elevated serum immunoglobulin E levels, an elevated eosinophil count with systemic manifestations, and eosinophilic infiltrates in other organs of the gastrointestinal tract. We present a case of eosinophilic pancreatitis in a 44-year-old man who was diagnosed after pancreatic resection for recurrent bouts of acute pancreatitis. While the gross and histologic evaluations matched other reported cases of eosinophilic pancreatitis, our patient had only minimal peripheral eosinophilia, no reported history of symptoms related to elevated eosinophilia or immunoglobulin E, and only mild eosinophilic infiltrates in his gallbladder.

Clinical characteristics of eosinophilic asthma exacerbations

DEFF Research Database (Denmark)

Bjerregaard, Asger; Laing, Ingrid A; Backer, Vibeke

2017-01-01

blood cell counts and a screening for common respiratory viruses and bacteria. An eosinophilic exacerbation (EE) was defined as having sputum eosinophils ≥ 3% and a non-eosinophilic exacerbation as NEE). RESULTS: A total of 47 patients were enrolled; 37 (79%) had successful sputum induction...... at baseline, of whom 43% had sputum eosinophils ≥3% (EE). Patients with EE had a significantly lower forced expiratory volume in 1 s (FEV1 ) % predicted (70.8%, P = 0.03) than patients with NEE (83.6%). Furthermore, EE patients were more likely to require supplemental oxygen during admission (63% vs 14%, P...... = 0.002). The prevalence of respiratory viruses was the same in EE and NEE patients (44% vs 52%, P = 0.60), as was bacterial infection (6% vs 14%, P = 0.44). Fractional expiratory nitric oxide (FeNO) correlated with sputum %-eosinophils (ρ = 0.57, P

Chronic eosinophilic pneumonia: a case report

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Heo, Tae Haeng; Park, Jeong Hee; Lim, Jong Nam; Shin, Hyun Jun; Jeon, Hae Jeong [College of Medicine, Kon-Kuk University, Seoul (Korea, Republic of)

1995-05-15

Chronic eosinophilic pneumonia is a rare disease characterized by chronic infiltration of the lung with eosinophils, usually associated with peripheral eosinophilia. In 65% of cases, the chest radiograph shows typical nonsegmental air-space consolidation confined to the outer third of the lung, and in 25% of cases, the 'photographic negative of pulmonary edema' Typical lung manifestations with peripheral eosinophilia are characteristic of chronic eosinophilic pneumonia. In the remaining cases, radiographic findings are nonspecific and require lung biopsy for confirmation. We report a case of chronic eosinophilic pneumonia in which chest radiograph and CT scans revealed bilateral patchy or diffuse opacity with nodules scattered throughout the lungs.

Eosinophils in helminth infection: defenders and dupes

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Huang, Lu; Appleton, Judith A.

2016-01-01

Eosinophilia is a central feature of the host response to helminth infection. Larval stages of parasitic worms are killed in vitro by eosinophils in the presence of specific antibodies or complement. These findings established host defense as the paradigm for eosinophil function. Recently, studies in eosinophil-ablated mouse strains have revealed an expanded repertoire of immunoregulatory functions for this cell. Other reports document crucial roles for eosinophils in tissue homeostasis and metabolism, processes that are central to the establishment and maintenance of parasitic worms in their hosts. In this review, we summarize current understanding of the significance of eosinophils at the host-parasite interface, highlighting their distinct functions during primary and secondary exposure. PMID:27262918

Eosinophils: important players in humoral immunity.

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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. © 2015 British Society for Immunology.

Leukemia -- Eosinophilic

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... social workers, and patient advocates. Cancer.Net Guide Leukemia - Eosinophilic Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

Evidence for eosinophil degranulation in acute appendicitis

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Santosh G

2008-04-01

Full Text Available Finding of increased numbers of eosinophils in the muscle in cases of acute appendicitis has led to the hypothesis that it may have an allergic origin. This study aimed to measure the eosinophil degranulation resulting in a rise in the serum of eosinophil granule proteins that would be expected in such cases. The levels of serum eosinophil cationic protein (ECP measured by chemiluminescence assay in acute appendicitis were compared, with those of appropriate controls. Mean (95% CI serum ECP (µg/L levels were: acute appendicitis 45.3 (27.7-63.0; normal appendix 22.7 (16.0-29.3; asthma 24.2 (4.6-43.8; and healthy volunteers 13.2 (8.3-18.1. In cases of acute appendicitis, there is an inverse relationship between duration of symptoms and serum ECP. However, this was not statistically significant. Significant local eosinophil activation and degranulation occurs in acute appendicitis, enough to cause a rise in serum levels of eosinophil chemotactic protein

Imipenem/cilastatin-induced acute eosinophilic pneumonia.

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

2016-03-04

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. 2016 BMJ Publishing Group Ltd.

Eosinophilic colitis in infants.

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Lozinsky, Adriana Chebar; Morais, Mauro Batista de

2014-01-01

To review the literature for clinical data on infants with allergic or eosinophilic colitis. MEDLINE search of all indexes was performed using the words "colitis or proctocolitis and eosinophilic" or "colitis or proctocolitis and allergic" between 1966 and February of 2013. All articles that described patients' characteristics were selected. A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263) of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 per high-power field) in 89.3% (236/264) of patients. Most patients showed improvement with the removal of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients). Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow's milk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Eosinophilic colitis in infants

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Adriana Chebar Lozinsky

2014-01-01

Full Text Available OBJECTIVE: To review the literature for clinical data on infants with allergic or eosinophilic colitis. DATA SOURCE: MEDLINE search of all indexes was performed using the words ''colitis or procto-colitis and eosinophilic'' or ''colitis or proctocolitis and allergic'' between 1966 and February of 2013. All articles that described patients' characteristics were selected. DATA SYNTHESIS: A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263 of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 perhigh-power field in 89.3% (236/264 of patients. Most patients showed improvement with theremoval of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients. CONCLUSIONS: Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow'smilk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure.

Eosinophils: changing perspectives in health and disease

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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

Esophageal involvement in eosinophilic gastroenteritis

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Matzinger, M A; Daneman, A

1983-02-01

The radiologic appearance of esophageal involvement due to eosinophilic gastroenteritis in a 15-year-old boy is presented. The lower two thirds of the esophagus was narrowed and the peristalsis diminished. The mucosa appeared smooth. This is the fourth reported case of esophageal involvement in eosinophilic gastroenteritis.

Eosinophilic Fasciitis Associated with Myositis

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Yuko Adachi

2015-04-01

Full Text Available Eosinophilic fasciitis is clinically characterized by symmetrical scleroderma-like indurations of the skin with pain. The histological features are fascial inflammation with lymphocytes and eosinophils as well as thickened and fibrotic fascia. Lymphocytic infiltration and degeneration of the underlying muscle are rarely observed. We report a 69-year-old Japanese woman who presented with multiple areas of glossy induration and painful peau d'orange-like lesions on the chest and four extremities. T2-weighted magnetic resonance imaging showed significant hyperintense thickening of the fascia of the lower extremities. Histopathological examination of a biopsy specimen from the induration showed marked fibrinoid degeneration of the fascia and the neighboring muscle with mixed cellular infiltration of lymphocytes and eosinophils. The predominant CD8+ lymphocytic infiltrates were observed by immunohistological study. A diagnosis of eosinophilic fasciitis with myositis was made. Oral administration of prednisolone and discontinuation of exercise significantly improved the lesions and pain.

Eosinophils in mucosal immune responses

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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

Genetics Home Reference: PDGFRB-associated chronic eosinophilic leukemia

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... associated chronic eosinophilic leukemia PDGFRB-associated chronic eosinophilic leukemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description PDGFRB -associated chronic eosinophilic leukemia is a type of cancer of blood-forming ...

Human versus mouse eosinophils: "that which we call an eosinophil, by any other name would stain as red".

Science.gov (United States)

Lee, James J; Jacobsen, Elizabeth A; Ochkur, Sergei I; McGarry, Michael P; Condjella, Rachel M; Doyle, Alfred D; Luo, Huijun; Zellner, Katie R; Protheroe, Cheryl A; Willetts, Lian; Lesuer, William E; Colbert, Dana C; Helmers, Richard A; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A

2012-09-01

The respective life histories of human subjects and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiologic pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils, their effector functions, or both. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide experimental details comparing and contrasting eosinophils and eosinophil effector functions in human subjects versus mice. In particular, our review will provide a summation and an easy-to-use reference guide to important studies demonstrating that although differences exist, more often than not, their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function but instead species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN). Detection by enzyme-linked immunosorbent assay and purification from normal human urine

DEFF Research Database (Denmark)

Reimert, C M; Minuva, U; Kharazmi, A

1991-01-01

Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN) is one of the cationic proteins found in the granules of the human eosinophilic granulocytes. EPX was purified from extracts of granules isolated from blood buffy coat cells of healthy donors. Polyclonal anti-EPX antibodies were...

EOSINOPHILS: MULTIFACETED BIOLOGIC PROPERTIES AND ROLES IN HEALTH AND DISEASE

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Kita, Hirohito

2011-01-01

Summary Eosinophils are leukocytes resident in mucosal tissues. During Th2-type inflammation, eosinophils are recruited from bone marrow and blood to the sites of immune response. While eosinophils have been considered end-stage cells involved in host protection against parasite infection and immunopathology in hypersensitivity disease, recent studies changed this perspective. Eosinophils are now considered multifunctional leukocytes involved in tissue homeostasis, modulation of adaptive immune responses, and innate immunity to certain microbes. Eosinophils are capable of producing immunoregulatory cytokines and are actively involved in regulation of Th2-type immune responses. However, such new information does not preclude earlier observations showing that eosinophils, in particular human eosinophils, are also effector cells with pro-inflammatory and destructive capabilities. Eosinophils with activation phenotypes are observed in biological specimens from patients with disease, and deposition of eosinophil products is readily seen in the affected tissues from these patients. Therefore, it would be reasonable to consider the eosinophil a multifaceted leukocyte that contributes to various physiological and pathological processes depending on their location and activation status. This review summarizes the emerging concept of the multifaceted immunobiology of eosinophils and discusses the roles of eosinophils in health and disease and the challenges and perspectives in the field. PMID:21682744

Blood eosinophil levels as a biomarker in COPD.

Science.gov (United States)

Brusselle, Guy; Pavord, Ian D; Landis, Sarah; Pascoe, Steven; Lettis, Sally; Morjaria, Nikhil; Barnes, Neil; Hilton, Emma

2018-05-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder and patients respond differently to treatment. Blood eosinophils are a potential biomarker to stratify patient subsets for COPD therapy. We reviewed the value of blood eosinophils in predicting exacerbation risk and response to corticosteroid treatment in the available literature (PubMed articles in English; keywords: "COPD" and "eosinophil"; published prior to May 2017). Overall, clinical data suggest that in patients with a history of COPD exacerbations, a higher blood eosinophil count predicts an increased risk of future exacerbations and is associated with improved response to treatment with inhaled corticosteroids (in combination with long-acting bronchodilator[s]). Blood eosinophils are therefore a promising biomarker for phenotyping patients with COPD, although prospective studies are needed to assess blood eosinophils as a biomarker of corticosteroid response for this. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human vs. Mouse Eosinophils: “That which we call an eosinophil, by any other name would stain as red”

Science.gov (United States)

Lee, James J.; Jacobsen, Elizabeth A.; Ochkur, Sergei I; McGarry, Michael P.; Condjella, Rachel M.; Doyle, Alfred D.; Luo, Huijun; Zellner, Katie R.; Protheroe, Cheryl A.; Willetts, Lian; LeSuer, William E.; Colbert, Dana C.; Helmers, Richard A.; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A.

2012-01-01

The respective life histories of humans and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiological pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils and/or their effector functions. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide the experimental details, comparing and contrasting eosinophils and eosinophil effector functions in humans vs. mice. In particular, our review will provide a summation and an easy to use reference guide to important studies demonstrating that while differences exist, more often than not their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function, but instead, species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients. PMID:22935586

Eosinophilic Esophagitis: MedlinePlus Health Topic

Science.gov (United States)

... Esophagitis (EoE) (American Academy of Allergy, Asthma, and Immunology) Also in Spanish Latest News Eosinophilic Esophagitis May ... Pediatric and Adolescent Patients (American College of Gastroenterology) Topic Image Related Health Topics Eosinophilic Disorders Esophagus Disorders ...

Preparation and surface labeling of murine eosinophils

International Nuclear Information System (INIS)

Burgess, A.W.; Cruise, K.M.; Mitchell, G.F.; Watt, S.M.

1980-01-01

Eosinophilic polymorphonuclear leukocytes were isolated from the peritoneal cavity of BALB/c mice infected with the parasite Mesocestoides corti. Approximately 4 x 10 7 eosinophils (purity, 50%) could be harvested from each mouse. A high yield and purity of eosinophils was obtained from the peritoneal cells of infected male BALB/c mice using density centrifugation on a gradient of slightly hypotonic colloidal silica sol (Percoll). After initial irradiation of the mice to lower the lymphocyte contamination, subsequent density gradient (and where nescessary sedimentation velocity) centrifugation yielded 10 8 eosinophils (purity >95%) from six to eight mice. It was also possible to isolate small numbers of eosinophils (2 x 10 4 cells/minute, purity >99%) without irradiating the mice. This could be achieved by separating the density gradient purified peritoneal cells by light-scatter on a Becton-Dickinson cell sorter (FACS II). Analysis of proteins extracted from eosinophils using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed a group of high molecular weight proteins (between 250K and 160K) which were not as distinctive in the neutrophil profile. Surface labeling was performed, before the cell separation, by using 125 I and 1,3,4,6-tetrachloro-3α,6α-diphenylglycoluril. Only five 125 I-labeled proteins were detected initially (all with apparent molecular weights >50,000). No 125 I appeared to be associated with actin under the conditions used for surface labeling. Four of the eosinophil surface labeled proteins corresponded to surface labeled proteins on neutrophils, but the major surface component of the eosinophils (MW 79,000) appeared to be smaller than the major neutrophil protein (MW 90,000). (author)

Eosinophilic esophagitis

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... of the American Academy of Allergy, Asthma and Immunology. Dietary therapy and nutrition management of eosinophilic esophagitis: ... of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol Pract . 2017;5(2): ...

Atypical presentations of eosinophilic fasciitis

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Tulin Ergun

2016-01-01

Full Text Available Eosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia.

Cyclin-dependent kinase 5 regulates degranulation in human eosinophils.

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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. © 2014 John Wiley & Sons Ltd.

Eosinophilic fasciitis

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Karolina Niklas

2015-01-01

Full Text Available Eosinophilic fasciitis is a rare connective tissue disease with unclear etiology and pathogenesis. It is classified as a scleroderma-like syndrome. The disease is characterized by fibrosis of the skin and subcutaneous tissues with significant thickening of fascia. Visceral involvement is rare. Characteristic feature in laboratory tests is peripheral blood eosinophilia. Differential diagnosis should be performed, including ruling out systemic sclerosis, nephrogenic systemic fibrosis, eosinophilia-myalgia syndrome, scleromyxedema, hypereosinophilic syndrome or Churg-Strauss syndrome. Final diagnosis is confirmed by histopathological examination. In treatment of the disease corticosteroids and/or immunosuppressive drugs are used. Some other drugs showed activity in this disease e.g. dapsone, infiximab or rituximab. Prognosis is rather good but sometimes a long-term treatment is necessary. In this paper we summarized the current knowledge on eosinophilic fasciitis.

Histopathologic diagnosis of eosinophilic conditions in the gastrointestinal tract.

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Hurrell, Jennifer M; Genta, Robert M; Melton, Shelby D

2011-09-01

Eosinophils, a constitutive component of the columnar-lined gastrointestinal tract, play an essential role in allergic responses and parasitic infections. The tissue density of these cells also increases in a variety of conditions of uncertain etiology. With the exception of the esophageal squamous epithelium, in which no eosinophils are normally present, the population of normal eosinophils in the remainder of the luminal gut is poorly defined. Therefore, histopathologists must rely on their subjective judgment to determine when a diagnosis of eosinophilic gastritis, enteritis, or colitis should be rendered. Eosinophilic esophagitis is currently the best defined and most studied eosinophilic condition of the digestive tract; therefore, the confidence in accurate diagnosis is increasing. In contrast, the characteristic clinicopathologic features of eosinophilic conditions affecting other parts of the digestive tract remain somewhat elusive. This review was designed to present pathologists with simple and practical information for the biopsy-based histopathologic diagnosis of eosinophilic esophagitis, gastritis, enteritis, and colitis. It was prepared by critically reviewing more than 200 articles on the topic, along with incorporating evidence accumulated through our own collective experience. We anticipate that by increasing pathologists' confidence in reporting these abnormal but often nameless eosinophilic infiltrates, we can help better define and characterize their significance.

Eosinophilic Chronic Rhinosinusitis in Japan

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Junichi Ishitoya

Full Text Available ABSTRACT: Chronic rhinosinusitis is a heterogeneous disease. In Europe and the United States, it has recently been divided into two subgroups: chronic rhinosinusitis with nasal polyps (CRSwNP and chronic rhinosinusitis without nasal polyps (CRSsNP. The majority of CRSwNP cases have a strong tendency to recur after surgery and show eosinophil-dominant inflammation. However, this definition has proved difficult to apply in Japan and East Asia, because more than half of the CRSwNP cases do not exhibit eosinophil-dominant inflammation in these areas of the world. In Japan in the 1990s, refractory CRSwNP to the standard treatment was focused on in clinical studies and the term ''eosinophilic chronic rhinosinusitis'' (ECRS was introduced to identify this subgroup of chronic rhinosinusitis in 2001.ECRS is different from non-ECRS in terms of many clinical features: symptom appearance, occurrence site of nasal polyps, CT scan findings, the histology of nasal polyps, blood examination findings, clinical course after surgery, and co-morbid asthma, etc. In this review, we describe these clinical features and mention how to make a clinical diagnosis of ECRS as well as how to treat it. Finally, we discuss the pathophysiology of ECRS. The concept of ECRS in Japan would be applicable for CRSwNP in other countries including Europe and the United States. KEY WORDS: chronic rhinosinusitis, clinical feature, diagnosis, eosinophilic chronic rhinosinusitis, eosinophils

T-helper 2 cytokines, transforming growth factor β1, and eosinophil products induce fibrogenesis and alter muscle motility in patients with eosinophilic esophagitis.

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Rieder, Florian; Nonevski, Ilche; Ma, Jie; Ouyang, Zhufeng; West, Gail; Protheroe, Cheryl; DePetris, Giovanni; Schirbel, Anja; Lapinski, James; Goldblum, John; Bonfield, Tracey; Lopez, Rocio; Harnett, Karen; Lee, James; Hirano, Ikuo; Falk, Gary; Biancani, Piero; Fiocchi, Claudio

2014-05-01

Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEFs), human esophageal muscle cells (HEMCs), and esophageal muscle strips to eosinophil-derived products. Biopsy specimens were collected via endoscopy from the upper, middle, and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls). Primary cultures of esophageal fibroblasts and muscle cells were derived from 12 freshly resected human esophagectomy specimens. Eosinophil distribution was investigated by histologic analyses of full-thickness esophageal tissue. Active secretion of EoE-related mediators was assessed from medium underlying mucosal biopsy cultures. We quantified production of fibronectin and collagen I by HEF and HEMC in response to eosinophil products. We also measured the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by, and adhesion of human eosinophils to, HEFs and HEMCs. Eosinophil products were tested in an esophageal muscle contraction assay. Activated eosinophils were present in all esophageal layers. Significantly higher concentrations of eosinophil-related mediators were secreted spontaneously in mucosal biopsy specimens from patients with EoE than controls. Exposure of HEFs and HEMCs to increasing concentrations of eosinophil products or co-culture with eosinophils caused HEFs and HEMCs to increase secretion of fibronectin and collagen I; this was inhibited by blocking transforming growth factor β1 and p38 mitogen-activated protein kinase signaling. Eosinophil binding to HEFs and HEMCs increased after incubation of mesenchymal cells with eosinophil-derived products, and decreased after blockade of transforming growth factor β1 and p38 mitogen-activated protein kinase blockade. Eosinophil products reduced

Actin polymerisation at the cytoplasmic face of eukaryotic nuclei

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David-Watine Brigitte

2006-05-01

Full Text Available Abstract Background There exists abundant molecular and ultra-structural evidence to suggest that cytoplasmic actin can physically interact with the nuclear envelope (NE membrane system. However, this interaction has yet to be characterised in living interphase cells. Results Using a fluorescent conjugate of the actin binding drug cytochalasin D (CD-BODIPY we provide evidence that polymerising actin accumulates in vicinity to the NE. In addition, both transiently expressed fluorescent actin and cytoplasmic micro-injection of fluorescent actin resulted in accumulation of actin at the NE-membrane. Consistent with the idea that the cytoplasmic phase of NE-membranes can support this novel pool of perinuclear actin polymerisation we show that isolated, intact, differentiated primary hepatocyte nuclei support actin polymerisation in vitro. Further this phenomenon was inhibited by treatments hindering steric access to outer-nuclear-membrane proteins (e.g. wheat germ agglutinin, anti-nesprin and anti-nucleoporin antibodies. Conclusion We conclude that actin polymerisation occurs around interphase nuclei of living cells at the cytoplasmic phase of NE-membranes.

Cytoplasmic tail domain of glycoprotein B is essential for HHV-6 infection

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Mahmoud, Nora F. [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Faculty of Pharmacy, Suez Canal University, Ismailia (Egypt); Jasirwan, Chyntia [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, University of Indonesia (Indonesia); Kanemoto, Satoshi; Wakata, Aika; Wang, Bochao; Hata, Yuuki [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Nagamata, Satoshi [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe (Japan); Kawabata, Akiko [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Tang, Huamin [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Immunology, Nanjing Medical University, Nanjing (China); Mori, Yasuko, E-mail: ymori@med.kobe-u.ac.jp [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan)

2016-03-15

Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans-Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation. - Highlights: • Glycoprotein B (gB) is highly conserved among herpesviruses. • HHV-6 gB is also abundantly expressed in virions. • In the present study, we showed the function of HHV-6 gB cytoplasmic tail domain (CTD). • We found that deletion of gB CTD impairs the intracellular transport of gB protein to the trans-Golgi network (TGN), and CTD of gB is critical for HHV-6 propagation.

Cytoplasmic tail domain of glycoprotein B is essential for HHV-6 infection

International Nuclear Information System (INIS)

Mahmoud, Nora F.; Jasirwan, Chyntia; Kanemoto, Satoshi; Wakata, Aika; Wang, Bochao; Hata, Yuuki; Nagamata, Satoshi; Kawabata, Akiko; Tang, Huamin; Mori, Yasuko

2016-01-01

Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans-Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation. - Highlights: • Glycoprotein B (gB) is highly conserved among herpesviruses. • HHV-6 gB is also abundantly expressed in virions. • In the present study, we showed the function of HHV-6 gB cytoplasmic tail domain (CTD). • We found that deletion of gB CTD impairs the intracellular transport of gB protein to the trans-Golgi network (TGN), and CTD of gB is critical for HHV-6 propagation.

Human eosinophils constitutively express a unique serine protease, PRSS33.

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Toyama, Sumika; Okada, Naoko; Matsuda, Akio; Morita, Hideaki; Saito, Hirohisa; Fujisawa, Takao; Nakae, Susumu; Karasuyama, Hajime; Matsumoto, Kenji

2017-07-01

Eosinophils play important roles in asthma, especially airway remodeling, by producing various granule proteins, chemical mediators, cytokines, chemokines and proteases. However, protease production by eosinophils is not fully understood. In the present study, we investigated the production of eosinophil-specific proteases/proteinases by transcriptome analysis. Human eosinophils and other cells were purified from peripheral blood by density gradient sedimentation and negative/positive selections using immunomagnetic beads. Protease/proteinase expression in eosinophils and release into the supernatant were evaluated by microarray analysis, qPCR, ELISA, flow cytometry and immunofluorescence staining before and after stimulation with eosinophil-activating cytokines and secretagogues. mRNAs for extracellular matrix proteins in human normal fibroblasts were measured by qPCR after exposure to recombinant protease serine 33 (PRSS33) protein (rPRSS33), created with a baculovirus system. Human eosinophils expressed relatively high levels of mRNA for metalloproteinase 25 (MMP25), a disintegrin and metalloprotease 8 (ADAM8), ADAM10, ADAM19 and PRSS33. Expression of PRSS33 was the highest and eosinophil-specific. PRSS33 mRNA expression was not affected by eosinophil-activating cytokines. Immunofluorescence staining showed that PRSS33 was co-localized with an eosinophil granule protein. PRSS33 was not detected in the culture supernatant of eosinophils even after stimulation with secretagogues, but its cell surface expression was increased. rPRSS33 stimulation of human fibroblasts increased expression of collagen and fibronectin mRNAs, at least in part via protease-activated receptor-2 activation. Activated eosinophils may induce fibroblast extracellular matrix protein synthesis via cell surface expression of PRSS33, which would at least partly explain eosinophils' role(s) in airway remodeling. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier

Eosinophils from Physiology to Disease: A Comprehensive Review

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Yacoub, Mona-Rita; Ripa, Marco; Mannina, Daniele; Cariddi, Adriana; Saporiti, Nicoletta; Ciceri, Fabio; Castagna, Antonella; Dagna, Lorenzo

2018-01-01

Despite being the second least represented granulocyte subpopulation in the circulating blood, eosinophils are receiving a growing interest from the scientific community, due to their complex pathophysiological role in a broad range of local and systemic inflammatory diseases as well as in cancer and thrombosis. Eosinophils are crucial for the control of parasitic infections, but increasing evidence suggests that they are also involved in vital defensive tasks against bacterial and viral pathogens including HIV. On the other side of the coin, eosinophil potential to provide a strong defensive response against invading microbes through the release of a large array of compounds can prove toxic to the host tissues and dysregulate haemostasis. Increasing knowledge of eosinophil biological behaviour is leading to major changes in established paradigms for the classification and diagnosis of several allergic and autoimmune diseases and has paved the way to a “golden age” of eosinophil-targeted agents. In this review, we provide a comprehensive update on the pathophysiological role of eosinophils in host defence, inflammation, and cancer and discuss potential clinical implications in light of recent therapeutic advances. PMID:29619379

Eosinophilic esophagitis-endoscopic distinguishing findings

OpenAIRE

Caetano, Ana Célia; Gonçalves, Raquel; Rolanda, Carla

2012-01-01

Eosinophilic esophagitis (EE) is the most frequent condition found in a group of gastrointestinal disorders called eosinophilic gastrointestinal diseases. The hypothetical pathophysiological mechanism is related to a hypersensitivity reaction. Gastroesophageal reflux disease- like complaints not ameliorated by acid blockade or occasional symptoms of dysphagia or food impaction are likely presentations of EE. Due to its unclear pathogenesis and unspecific symptoms, it is difficult to diagnose ...

Management guidelines of eosinophilic esophagitis in childhood

DEFF Research Database (Denmark)

Papadopoulou, A; Koletzko, S; Heuschkel, R

2014-01-01

OBJECTIVES: Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. With few exceptions, 15 eosinophils per high-power field...... was obtained during 3 face-to-face meetings of the Gastroenterology Committee and 1 teleconference. RESULTS: The cornerstone of treatment is an elimination diet (targeted or empiric elimination diet, amino acid-based formula) and/or swallowed, topical corticosteroids. Systemic corticosteroids are reserved...

Thrombomodulin inhibits the activation of eosinophils and mast cells.

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

2015-01-01

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

Eosinophils from hematopoietic stem cell recipients suppress allogeneic T cell proliferation.

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Andersson, Jennie; Cromvik, Julia; Ingelsten, Madeleine; Lingblom, Christine; Andersson, Kerstin; Johansson, Jan-Erik; Wennerås, Christine

2014-12-01

Eosinophilia has been associated with less severe graft-versus-host disease (GVHD), but the underlying mechanism is unknown. We hypothesized that eosinophils diminish allogeneic T cell activation in patients with chronic GVHD. The capacity of eosinophils derived from healthy subjects and hematopoietic stem cell (HSC) transplant recipients, with or without chronic GVHD, to reduce allogeneic T cell proliferation was evaluated using a mixed leukocyte reaction. Eosinophil-mediated inhibition of proliferation was observed for the eosinophils of both healthy subjects and patients who underwent HSC transplantation. Eosinophils from patients with and without chronic GVHD were equally suppressive. Healthy eosinophils required cell-to-cell contact for their suppressive capacity, which was directed against CD4(+) T cells and CD8(+) T cells. Neither eosinophilic cationic protein, eosinophil-derived neurotoxin, indoleamine 2,3-dioxygenase, or increased numbers of regulatory T cells could account for the suppressive effect of healthy eosinophils. Real-time quantitative PCR analysis revealed significantly increased mRNA levels of the immunoregulatory protein galectin-10 in the eosinophils of both chronic GVHD patients and patients without GVHD, as compared with those from healthy subjects. The upregulation of galectin-10 expression in eosinophils from patients suggests a stimulatory effect of HSC transplantation in itself on eosinophilic galectin-10 expression, regardless of chronic GVHD status. To conclude, eosinophils from HSC transplant recipients and healthy subjects have a T cell suppressive capacity. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Eosinophilic Esophagitis: Relevance of Mast Cell Infiltration.

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

2018-05-17

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

Regulation of Spontaneous Eosinophil Apoptosis—A Neglected Area of Importance

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Pinja Ilmarinen

2014-01-01

Full Text Available Asthma is characterized by the accumulation of eosinophils in the airways in most phenotypes. Eosinophils are inflammatory cells that require an external survival-prolonging stimulus such as granulocyte macrophage-colony-stimulating factor (GM-CSF, interleukin (IL-5, or IL-3 for survival. In their absence, eosinophils are programmed to die by spontaneous apoptosis in a few days. Eosinophil apoptosis can be accelerated by Fas ligation or by pharmacological agents such as glucocorticoids. Evidence exists for the relevance of these survival-prolonging and pro-apoptotic agents in the regulation of eosinophilic inflammation in inflamed airways. Much less is known about the physiological significance and mechanisms of spontaneous eosinophil apoptosis even though it forms the basis of regulation of eosinophil longevity by pathophysiological factors and pharmacological agents. This review concentrates on discussing the mechanisms of spontaneous eosinophil apoptosis compared to those of glucocorticoid- and Fas-induced apoptosis. We aim to answer the question whether the external apoptotic stimuli only augment the ongoing pathway of spontaneous apoptosis or truly activate a specific pathway.

Eosinophilic cystitis

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Mosholt, Karina Sif Søndergaard; Dahl, Claus; Azawi, Nessn Htum

2014-01-01

Eosinophilic cystitis (EC) is a rare disease. We describe three cases, where presentations of the disease are similar. To highlight probable causes of the disease, symptoms, clinical findings and treatment modalities, we reviewed 56 cases over a 10-year period. The most common symptoms were...

Esophagitis dissecans associated with eosinophilic esophagitis in an adolescent

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Marjorie-Anne R. Guerra

2015-03-01

Full Text Available Esophagitis dissecans superficialis and eosinophilic esophagitis are distinct esophageal pathologies with characteristic clinical and histologic findings. Esophagitis dissecans superficialis is a rare finding on endoscopy consisting of the peeling of large fragments of esophageal mucosa. Histology shows sloughing of the epithelium and parakeratosis. Eosinophilic esophagitis is an allergic disease of the esophagus characterized by eosinophilic inflammation of the epithelium and symptoms of esophageal dysfunction. Both of these esophageal processes have been associated with other diseases, but there is no known association between them. We describe a case of esophagitis dissecans superficialis and eosinophilic esophagitis in an adolescent patient. To our knowledge, this is the first case describing an association between esophageal dissecans superficialis and eosinophilic esophagitis.

The potential implication of eosinophil activation in the pathogenesis ...

African Journals Online (AJOL)

Ehab

The potential implication of eosinophil activation in the pathogenesis of childhood asthma. INTRODUCTION. Asthma is recognized as an eosinophil mediated inflammation of the airways1. Eosinophils are major contributors to the damage in the airways of asthmatic patients which when activated, degranulate and release ...

Mast cells and eosinophils in invasive breast carcinoma

International Nuclear Information System (INIS)

Amini, Rose-Marie; Aaltonen, Kirsimari; Nevanlinna, Heli; Carvalho, Ricardo; Salonen, Laura; Heikkilä, Päivi; Blomqvist, Carl

2007-01-01

Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas. Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome. Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours. A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers

Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis

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Sato, Hiroki; Nakajima, Nao; Takahashi, Kazuya; Hasegawa, Go; Mizuno, Ken-ichi; Hashimoto, Satoru; Ikarashi, Satoshi; Hayashi, Kazunao; Honda, Yutaka; Yokoyama, Junji; Sato, Yuichi; Terai, Shuji

2017-01-01

AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder (EoGD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis (EoE), subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal myositis (EoEM), identified by endoscopy, manometry and serum immunoglobulin E levels (s-IgE), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples. RESULTS In five patients with EoE, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with sEoE and four with EoEM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with EoE and sEoE with some variation, while EoEM was associated with hypercontractile or hypertensive peristalsis, with elevated s-IgE. Histology revealed the following eosinophils per high-power field values. EoE = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; sEoE = 3 in the epithelium and 35 in the subepithelium (conventional biopsy); EoEM = none in the epithelium, 10.7 ± 11.7 in the subepithelium (conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria (peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to EoE. Eotaxin-3, IL-5 and IL-13 were overexpressed in EoE. CONCLUSION Based on clinical and histological data, we identified criteria, which differentiated between EoE, sEoE and EoEM, and reflected a different pathogenesis between these esophageal EoGDs. PMID:28428721

Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis.

Science.gov (United States)

Sato, Hiroki; Nakajima, Nao; Takahashi, Kazuya; Hasegawa, Go; Mizuno, Ken-Ichi; Hashimoto, Satoru; Ikarashi, Satoshi; Hayashi, Kazunao; Honda, Yutaka; Yokoyama, Junji; Sato, Yuichi; Terai, Shuji

2017-04-07

To define clinical criteria to differentiate eosinophilic gastrointestinal disorder (EoGD) in the esophagus. Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis (EoE), subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal myositis (EoEM), identified by endoscopy, manometry and serum immunoglobulin E levels (s-IgE), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples. In five patients with EoE, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with sEoE and four with EoEM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with EoE and sEoE with some variation, while EoEM was associated with hypercontractile or hypertensive peristalsis, with elevated s-IgE. Histology revealed the following eosinophils per high-power field values. EoE = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; sEoE = 3 in the epithelium and 35 in the subepithelium (conventional biopsy); EoEM = none in the epithelium, 10.7 ± 11.7 in the subepithelium (conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria (peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to EoE. Eotaxin-3, IL-5 and IL-13 were overexpressed in EoE. Based on clinical and histological data, we identified criteria, which differentiated between EoE, sEoE and EoEM, and reflected a different pathogenesis between these esophageal EoGDs.

Eosinophilic esophagitis: manometric and pHmetric findings

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Monica Maria Cardoso Monnerat

2012-06-01

Full Text Available CONTEXT: Eosinophilic esophagitis is an entity characterized by an esophageal inflammatory infiltrate of eosinophils, manifested by dysphagia, intermittent food impactions and symptoms similar to gastroesophageal reflux disease (GERD, that predominantly affects young adults. There may be association of eosinophilic esophagitis with GERD, and motor abnormalities have been described. OBJECTIVE: The main objectives of this study are to describe the findings at esophageal manometry and pH monitoring in patients with eosinophilic esophagitis. METHODS: Cross-sectional study of 20 patients with a diagnosis of eosinophilic esophagitis, submitted to esophageal manometry and 24h pH monitoring. Were analysed the manometric changes and the presence of abnormal reflux on pH monitoring. RESULTS: Twenty patients (15 men, 5 women had a mean age of 29 years. Motility disorders were found in 25% (5/20 patients with ineffective esophageal motility being the most common finding. pH monitoring revealed abnormal reflux on 25%, without any relationship with manometric findings. CONCLUSIONS: Manometric abnormalities were observed in 25% of patients and abnormal reflux on pH monitoring also in 25%. This study showed no relationship between abnormal reflux and the presence of manometric changes.

2013 Update on Celiac Disease and Eosinophilic Esophagitis

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Marco Astegiano

2013-08-01

Full Text Available 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.

Eosinophilic gastroenteritis with Splendore-Hoeppli material in the ferret (Mustela putorius furo).

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Fox, J G; Palley, L S; Rose, R

1992-01-01

Eosinophilic gastroenteritis, focal or diffuse with eosinophilic infiltrations of the stomach or intestine, has been described in human beings, cats, dogs, and horses. In this paper, we describe infiltration of the gastrointestinal tract with eosinophils accompanied by a circulating eosinophilia in six ferrets (Mustela putorius furo). Clinical signs included chronic weight loss, anorexia, and diarrhea. The small intestines from five ferrets had diffuse infiltrates of eosinophils. This resulted in focal or multifocal loss of the muscular tunic in three ferrets. Two of these ferrets also had eosinophilic gastritis. Eosinophilic granulomas with Splendore-Hoeppli material were present in mesenteric lymph nodes in four ferrets. Two ferrets had multiple organ involvement; one had eosinophilic granulomas in the liver, mesentery, and choroid plexus as well as moderate parapancreatic segmental arteritis with infiltration of eosinophils and mural thrombosis. The second ferret had, in addition to moderate diffuse gastric and small intestinal eosinophilic mucosal infiltrations, interstitial eosinophilic pulmonary infiltrates. Examination of all tissues failed to reveal an infectious agent.

Genetics Home Reference: PDGFRA-associated chronic eosinophilic leukemia

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... link) Genetic Testing Registry: Idiopathic hypereosinophilic syndrome Other Diagnosis and Management Resources (3 links) Cancer.Net: Leukemia - Eosinophilic: Treatment MedlinePlus Encyclopedia: Eosinophil Count - Absolute Seattle ...

Emerging Roles for Eosinophils in the Tumor Microenvironment.

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Reichman, Hadar; Karo-Atar, Danielle; Munitz, Ariel

2016-11-01

Eosinophils are evolutionary conserved cells largely studied in the context of allergy. Although eosinophils were first described in tumors more than 120 years ago, their roles in cancer are often overlooked. This is puzzling given their potent immune modulatory, cytotoxic, and/or tissue repair capabilities, and recent studies demonstrating key roles for eosinophils in contexts far beyond their 'classical' field (e.g., metabolism, thermogenesis, and tissue regeneration). Recent data suggest that this frequently ignored cell is emerging as a potent immune effector and immune modulator in the tumor microenvironment. This review discusses the relevance of eosinophils to tumorigenesis and the potential to harness their function in cancer therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

New Insights into Eosinophilic Otitis Media.

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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.

Eosinophilic ascites: A case report and literature review

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Raed M Alsulaiman

2015-01-01

Full Text Available 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.

Cytological diagnostic of lymphadenitis tuberculosis by eosinophilic material

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Delyuzar; Amir, Z.; Kusumawati, L.

2018-03-01

AFB sputum and chest X-ray are used to identify patients with pulmonary TB. For extrapulmonary TB, fine needle aspiration cytology is needed, even though occasionally found not atypical feature in the form of eosinophilic material with dark brown particles, suspected as TB. This research was to show that eosinophilic material with dark brown particles is accurate as new criteria for the cytological diagnosis of TB. By performing fine needle aspiration biopsy stained with Giemsa, if an eosinophilic material with dark brown particles was encountered, we continued with Ziehl-Neelsen AFB stain and confirmed with PCR. To assess accuracy, we used a diagnostic test to evaluate sensitivity and specificity of eosinophilic material with dark brown particles by using AFB and PCR as the gold standard. The sensitivity and specificity of cytological diagnosis in tuberculosis of eosinophilic material with dark brown particles were 93.65% and 70.99%, respectively if confirmed with AFB. On the other hand, if confirmed with PCR using Mycobacterium tuberculosis DNA, the sensitivity and specificity were 98.95% and 96.79%, respectively. In conclusion, eosinophilic masses with dark brown particles is accurate as new criteria of TB diagnostic cytology with high sensitivity and specificity confirmed with AFB and PCR test.

Eosinophils are rare in biopsy specimens of psoriasis vulgaris.

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Rosa, Gabriela; Fernandez, Anthony P; Schneider, Sarah; Billings, Steven D

2017-12-01

Histological features of lesional biopsies can be helpful in distinguishing psoriasis subtypes from disease mimickers. However, occasionally, classic histological features are not sufficient for distinction, and additional clues would be useful. There is a common belief that the presence of eosinophils in skin biopsies argues against psoriasis, but actual literature is scant. Skin biopsies with a diagnosis of psoriasis from 2013 to 2016 were reviewed. For inclusion, both histological and clinical features were required to be consistent with psoriasis. For biopsies meeting inclusion criteria, a detailed evaluation for typical histological parameters of psoriasis, as well as presence of dermal eosinophils, was performed. Of 85 cases meeting inclusion criteria, all had either individual or grouped intracorneal neutrophils and dilated papillary blood vessels. Diminished or complete loss of the granular cell layer was seen in 83 cases (98%), and parakeratosis was seen in 84 cases (99%). Alternatively, dermal eosinophils were seen in only 15 cases (18%). Of cases with eosinophils, none had more than 3 eosinophils upon examination of the entire dermis. Active treatment did not appear to impact presence/absence or numbers of eosinophils. Eosinophils are uncommon in psoriasis biopsies, and when present, they are found in small numbers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eosinophils in Homeostasis and Their Contrasting Roles during Inflammation and Helminth Infections.

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Strandmark, Julia; Rausch, Sebastian; Hartmann, Susanne

2016-01-01

Eosinophil numbers are highly elevated during helminth infections and a range of allergic and inflammatory disorders, but eosinophils are also present in several tissues in the absence of infection. Indeed, new findings demonstrate that eosinophils may be involved in events as diverse as glucose metabolism, mammary gland development, intestinal health, tissue remodeling, thymic selection, and B-cell survival. Although eosinophils often correlate with pathological parameters during conditions such as inflammatory bowel disease and asthma, the evidence for their contribution to tissue pathology remains controversial. Recent research suggests that eosinophils may have additional roles in these settings that are related to control and resolution of inflammation. Controversy also surrounds the involvement of eosinophils in anti-helminth immunity. Their assumed role in fighting parasites has increasingly been questioned, particularly as a result of data from studies of eosinophil-ablated mouse strains in which either no or only very moderate effects on helminth survival has been reported. Helminths are masters of immune regulation, but whether they actively suppress eosinophil function has rarely been considered. Thus, the purpose of this review is threefold: (1) to summarize our knowledge of the wide range of functions of eosinophils during homeostasis, (2) to discuss the role of eosinophil during inflammation and the recent discovery of eosinophils as mediators of inflammatory resolution, and (3) to summarize data on the effect of eosinophils on helminth infections and discuss the possibility of helminth-mediated modulation of eosinophils.

STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides

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Fredholm, Simon; Gjerdrum, Lise Mette R; Willerslev-Olsen, Andreas

2014-01-01

Eosinophil granulocytes have been implicated in anticancer immunity but recent data indicate that eosinophils can also promote cancer. Herein, we studied eosinophils in skin lesions from 43 patients with mycosis fungoides (MF). The presence of eosinophils correlated with disease stage: 78......% of patients with advanced disease displayed eosinophil infiltration, whereas this was only seen in 11% of patients with patches (p...) in malignant T-cells also stained positively for eosinophils, whereas this was only observed in 28% of pY-STAT3-negative patients (peosinophilic activation and trafficking factors: High-mobility group BOX-1 protein (HMGB1) and interleukin 5 (IL5). STAT3 si...

Exosome secretion by eosinophils: A possible role in asthma pathogenesis.

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Mazzeo, Carla; Cañas, José Antonio; Zafra, Maria Paz; Rojas Marco, Ainara; Fernández-Nieto, Mar; Sanz, Veronica; Mittelbrunn, María; Izquierdo, Manuel; Baixaulli, Francesc; Sastre, Joaquín; Del Pozo, Victoria

2015-06-01

Eosinophils secrete several granules that are involved in the propagation of inflammatory responses in patients with pathologies such as asthma. We hypothesized that some of these granules are exosomes, which, when transferred to the recipient cells, could modulate asthma progression. Eosinophils were purified from peripheral blood and cultured with or without IFN-γ or eotaxin. Multivesicular bodies (MVBs) in eosinophils were studied by using fluorescence microscopy, transmission electron microscopy (TEM), and flow cytometry. Exosome secretion was measured and exosome characterization was performed with TEM, Western blotting, and NanoSight analysis. Generation of MVBs in eosinophils was confirmed by using fluorescence microscopy and flow cytometry and corroborated by means of TEM. Having established that eosinophils contain MVBs, our aim was to demonstrate that eosinophils secrete exosomes. To do this, we purified exosomes from culture medium of eosinophils and characterized them. Using Western blot analysis, we demonstrated that eosinophils secreted exosomes and that the discharge of exosomes to extracellular media increases after IFN-γ stimulation. We measured exosome size and quantified exosome production from healthy and asthmatic subjects using nanotracking analysis. We found that exosome production was augmented in asthmatic patients. Our findings are the first to demonstrate that eosinophils contain functional MVBs and secrete exosomes and that their secretion is increased in asthmatic patients. Thus exosomes might play an important role in the progression of asthma and eventually be considered a biomarker. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

CXCR3 expression and activation of eosinophils

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Jinquan, T; Jing, C; Jacobi, H H

2000-01-01

CXC chemokine receptor 3 (CXCR3), predominately expressed on memory/activated T lymphocytes, is a receptor for both IFN-gamma-inducible protein-10 (gamma IP-10) and monokine induced by IFN-gamma (Mig). We report a novel finding that CXCR3 is also expressed on eosinophils. gamma IP-10 and Mig induce...... in eosinophils are up- and down-regulated by IL-2 and IL-10, respectively, as detected using flow cytometry, immunocytochemical assay, and a real-time quantitative RT-PCR technique. gamma IP-10 and Mig act eosinophils to induce chemotaxis via the cAMP-dependent protein kinase A signaling pathways. The fact...

Nutritional management of Eosinophilic Gastroenteropathies: Case series from the community

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Basilious Alfred

2011-05-01

Full Text Available Abstract Eosinophilic gastroenteropathies, such as eosinophilic esophagitis and eosinophilic colitis, have classically been treated with swallowed inhaled corticosteroids or oral corticosteroids. More recent studies have found elimination and elemental diets to be effective treatment alternatives to steroids. In this case series we describe the treatment of three children using nutritional management in a community setting. Elimination diets and elemental diets based on patch testing and skin prick tests reduced the eosinophil counts to normal levels in all three children. Food items which tested positive were then reintroduced while symptoms and eosinophil counts were monitored. Nutritional management of eosinophilic esophagitis and eosinophilic colitis was found to be effective in reducing symptoms. However, obstacles facing patients who choose this type of therapy include limitations due to the cost of repeated endoscopies, palatability of elimination/elemental diets and the availability of subspecialists trained in management (e.g. Allergy, Gastroenterology, and Pathology. It may be a worthwhile endeavour to overcome these obstacles as nutritional management minimizes the potential long-term effects of chronic steroid therapy.

The expanding role(s) of eosinophils in health and disease

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Jacobsen, Elizabeth A.; Helmers, Richard A.

2012-01-01

Surprisingly, the role(s) of eosinophils in health and disease is often summarized by clinicians and basic research scientists as a pervasive consensus opinion first learned in medical/graduate school. Eosinophils are rare white blood cells whose activities are primarily destructive and are only relevant in parasitic infections and asthma. However, is this consensus correct? This review argues that the wealth of available studies investigating the role(s) of eosinophils in both health and disease demonstrates that the activities of these granulocytes are far more expansive and complex than previously appreciated. In turn, this greater understanding has led to the realization that eosinophils have significant contributory roles in a wide range of diseases. Furthermore, published studies even implicate eosinophil-mediated activities in otherwise healthy persons. We suggest that the collective reports in the literature showing a role for eosinophils in an ever-increasing number of novel settings highlight the true complexity and importance of this granulocyte. Indeed, discussions of eosinophils are no longer simple and more often than not now begin with the question/statement “Did you know …?” PMID:22936660

Asthma Control and Sputum Eosinophils: A Longitudinal Study in Daily Practice.

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Demarche, Sophie F; Schleich, Florence N; Paulus, Virginie A; Henket, Monique A; Van Hees, Thierry J; Louis, Renaud E

Longitudinal trials have suggested that asthma control may be influenced by fluctuations in eosinophilic inflammation. This association has however never been confirmed in daily practice. To investigate the relationship between asthma control and sputum eosinophils in clinical practice. A retrospective longitudinal study was conducted on 187 patients with asthma with at least 2 successful sputum inductions at our Asthma Clinic. Linear mixed models were used to assess the relationship between asthma control and individual changes in sputum eosinophils. Receiver-operating characteristic curves were constructed to define minimal important differences (MIDs) of sputum eosinophils associated with a change of at least 0.5 in Asthma Control Questionnaire (ACQ) score. Then, a validation cohort of 79 patients with asthma was recruited to reassess this relationship and the accuracy of the MID values. A multivariate analysis showed that asthma control was independently associated with individual fluctuations in sputum eosinophil count (P eosinophilic asthma, we calculated a minimal important decrease of 4.3% in the percentage of sputum eosinophils (area under the curve [AUC], 0.69; P eosinophils and the accuracy of the MIDs of sputum eosinophils were confirmed in the validation cohort. At the individual level, asthma control was associated with fluctuations in sputum eosinophil count over time. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs.

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Wicher, Sarah A; Jacoby, David B; Fryer, Allison D

2017-06-01

Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals. Copyright �

Feline familial pedal eosinophilic dermatosis in two littermates

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Charline Pressanti

2015-04-01

Full Text Available In cats, the most common eosinophilic dermatoses are feline miliary dermatitis and eosinophilic granuloma complex. The most commonly identified underlying cause is a hypersensitivity reaction. Few cases of familial forms of eosinophilic dermatoses are reported in the literature. Two young adult cats from the same litter presented 2 years apart with a severe and chronic fluid or tissue infiltration of the distal part of several limbs. Lesions started on the forelegs and developed on the other limbs. Cytological and histopathological examinations showed lesions consistent with an atypical form of feline eosinophilic dermatosis associated with secondary bacterial infection. In both cats, antibiotics combined with immunosuppressive treatment partially improved the lesions, which continued to progress on a waxing and waning course, even in the absence of treatment. Allergy work-up did not permit the identification of an underlying allergic triggering factor. The severity of the lesions, the unusual presentation and the unsatisfactory response to immunosuppressive therapy in two feline littermates suggested a genetic form of eosinophilic dermatosis.

Extracellular microvesicle production by human eosinophils activated by “inflammatory” stimuli

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Praveen Akuthota

2016-10-01

Full Text Available A key function of human eosinophils is to secrete cytokines, chemokines and cationic proteins, trafficking and releasing these mediators for roles in inflammation and other immune responses. Eosinophil activation leads to secretion of pre-synthesized granule-stored mediators through different mechanisms, but the ability of eosinophils to secrete extracellular vesicles (EVs, very small vesicles with preserved membrane topology, is still poorly understood. In the present work, we sought to identify and characterize EVs released from human eosinophils during different conditions: after a culturing period or after isolation and stimulation with inflammatory stimuli, which are known to induce eosinophil activation and secretion: CCL11 (eotaxin-1 and tumor necrosis factor alpha (TNF-α. EV production was investigated by nanoscale flow cytometry, conventional transmission electron microscopy (TEM and pre-embedding immunonanogold EM. The tetraspanins CD63 and CD9 were used as EV biomarkers for both flow cytometry and ultrastructural immunolabeling. Nanoscale flow cytometry showed that human eosinophils produce EVs in culture and that a population of EVs expressed detectable CD9, while CD63 was not consistently detected. When eosinophils were stimulated immediately after isolation and analyzed by TEM, EVs were clearly identified as microvesicles (MVsoutwardly budding off the plasma membrane. Both CCL11 and TNF-α induced significant increases of MVs compared to unstimulated cells.TNF-α induced amplified release of MVs more than CCL11. Eosinophil MV diameters varied from 20-1000 nm. Immunonanogold EM revealed clear immunolabeling for CD63 and CD9 on eosinophil MVs, although not all MVs were labeled. Altogether, we identified, for the first time, that human eosinophils secrete MVs and that this production increases in response to inflammatory stimuli. This is important to understand the complex secretory activities of eosinophils underlying immune

Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease

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Tashkin DP

2018-01-01

Full Text Available Donald P Tashkin,1 Michael E Wechsler2 1Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2Department of Medicine, National Jewish Health, Denver, CO, USA Abstract: COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. Keywords: lung disease, pulmonary diseases, corticosteroids, asthma, pneumonia

Chronic eosinophilic pneumonia presenting with ipsilateral pleural effusion: a case report.

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Sriratanaviriyakul, Narin; La, Hanh H; Albertson, Timothy E

2016-08-12

Chronic eosinophilic pneumonia is a rare idiopathic interstitial lung disease. The nearly pathognomonic radiographic finding is the peripheral distribution of alveolar opacities. Pleural effusions are rarely seen. We report a case of chronic eosinophilic pneumonia with transudative eosinophilic pleural effusion. A 57-year-old Hispanic woman, a nonsmoker with a history of controlled asthma, presented to the hospital with unresolving pneumonia despite three rounds of antibiotics over a 2-month period. She was later diagnosed with chronic eosinophilic pneumonia based on the presence of peripheral blood eosinophilia, the peripheral distribution of alveolar infiltrates on chest radiograph, and a lung parenchymal biopsy with infiltrates of eosinophils. Upon presentation, our patient had a right-sided moderate-sized pleural effusion. The pleural fluid profile was consistent with a transudative effusion with eosinophil predominance. Our patient responded promptly to oral corticosteroid treatment in a few days. The pulmonary infiltrates and pleural effusion subsided on a 1-month follow-up chest radiograph after starting corticosteroid treatment. We report the first case of chronic eosinophilic pneumonia presenting with pneumonia with ipsilateral transudative eosinophilic pleural effusion. Like other cases of chronic eosinophilic pneumonia, early recognition and diagnosis is essential and prompt treatment with corticosteroids is the mainstay of therapy. Pleural effusion resolved without the further need for therapeutic thoracentesis.

Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis.

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Petsky, Helen L; Cates, Chris J; Kew, Kayleigh M; Chang, Anne B

2018-06-01

Asthma guidelines guide health practitioners to adjust treatments to the minimum level required for asthma control. As many people with asthma have an eosinophilic endotype, tailoring asthma medications based on airway eosinophilic levels (sputum eosinophils or exhaled nitric oxide, FeNO) may improve asthma outcomes. To synthesise the evidence from our updated Cochrane systematic reviews, for tailoring asthma medication based on eosinophilic inflammatory markers (sputum analysis and FeNO) for improving asthma-related outcomes in children and adults. Cochrane reviews with standardised searches up to February 2017. The Cochrane reviews included randomised controlled comparisons of tailoring asthma medications based on sputum analysis or FeNO compared with controls (primarily clinical symptoms and/or spirometry/peak flow). The 16 included studies of FeNO-based management (seven in adults) and 6 of sputum-based management (five in adults) were clinically heterogeneous. On follow-up, participants randomised to the sputum eosinophils strategy (compared with controls) were significantly less likely to have exacerbations (62 vs 82/100 participants with ≥1 exacerbation; OR 0.36, 95% CI 0.21 to 0.62). For the FeNO strategy, the respective numbers were adults OR 0.60 (95% CI 0.43 to 0.84) and children 0.58 (95% CI 0.45 to 0.75). However, there were no significant group differences for either strategy on daily inhaled corticosteroids dose (at end of study), asthma control or lung function. Adjusting treatment based on airway eosinophilic markers reduced the likelihood of asthma exacerbations but had no significant impact on asthma control or lung function. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

GWAS identifies four novel eosinophilic esophagitis loci

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Sleiman, Patrick M. A.; 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 oesophagus 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

Focus on audiologic impairment in eosinophilic granulomatosis with polyangiitis.

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Seccia, Veronica; Fortunato, Susanna; Cristofani-Mencacci, Lodovica; Dallan, Iacopo; Casani, Augusto P; Latorre, Manuela; Paggiaro, Pierluigi; Bartoli, Maria Laura; Sellari-Franceschini, Stefano; Baldini, Chiara

2016-12-01

To evaluate the clinical features of audiologic impairment and its relationship with the nasal, vestibular, and rheumatologic profile in a cohort of patients with eosinophilic granulomatosis with polyangiitis (EGPA), formerly named Churg-Strauss syndrome. Prospective cross-sectional study. Thirty-nine patients with EGPA, considered controlled according to the Birmingham Vasculitis Activity Score and the Vasculitis Damage Index, underwent a complete audiologic evalutaion with otomicroscopy, impedance audiometry, speech audiometry, and auditory brainstem responses; rhinologic evaluation was made by means of fiberoptic endoscopy and nasal cytology; the clinical evaluation was completed with analysis of the facial function and, in patients with referred vertigo, with videonystagmography (VNG). Data were compared to the rheumatologic profile (eosinophil count, antineutrophil cytoplasmic antibodies status). Thirty-four of 39 patients fulfilled the inclusion criteria. Of those, 18 (52, 8%) were affected by variable degrees of hearing loss (sensorineural hearing loss [SNHL]) in four cases (11, 8%), mixed sensorineural and conductive hearing loss in two (5, 9%), presbycusis in six (17, 6%), and otitis media with effusion (OME) in six (17, 6%). Vestibular impairment was represented by benign paroxysmal positional vertigo and unspecific dizziness in three (8, 8%) and four cases (11, 8%), respectively, all with normal VNG. Ear involvement was statistically related to the EGPA vasculitic pattern and independent from the nasal impairment, cytology, and duration of nasal symptoms. No facial palsy was registered. In our experience, the largest in the existing literature, the otological involvement in EGPA is common and may occur variably as SNHL or OME. Otological involvement occurs early in the course of the disease process, but is nonspecific in making the diagnosis of EGPA. Its recognition is therefore fundamental. 4. Laryngoscope, 126:2792-2797, 2016. © 2016 The American

An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock.

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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.

An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock

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Miguel Martillo

2015-05-01

Full Text Available 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.

Effective antigen presentation to helper T cells by human eosinophils.

Science.gov (United States)

Farhan, Ruhaifah K; Vickers, Mark A; Ghaemmaghami, Amir M; Hall, Andrew M; Barker, Robert N; Walsh, Garry M

2016-12-01

Although eosinophils are inflammatory cells, there is increasing attention on their immunomodulatory roles. For example, murine eosinophils can present antigen to CD4 + T helper (Th) cells, but it remains unclear whether human eosinophils also have this ability. This study determined whether human eosinophils present a range of antigens, including allergens, to activate Th cells, and characterized their expression of MHC class II and co-stimulatory molecules required for effective presentation. Human peripheral blood eosinophils purified from non-allergic donors were pulsed with the antigens house dust mite extract (HDM), Timothy Grass extract (TG) or Mycobacterium tuberculosis purified protein derivative (PPD), before co-culture with autologous CD4 + Th cells. Proliferative and cytokine responses were measured, with eosinophil expression of HLA-DR/DP/DQ and the co-stimulatory molecules CD40, CD80 and CD86 determined by flow cytometry. Eosinophils pulsed with HDM, TG or PPD drove Th cell proliferation, with the response strength dependent on antigen concentration. The cytokine responses varied with donor and antigen, and were not biased towards any particular Th subset, often including combinations of pro- and anti-inflammatory cytokines. Eosinophils up-regulated surface expression of HLA-DR/DP/DQ, CD80, CD86 and CD40 in culture, increases that were sustained over 5 days when incubated with antigens, including HDM, or the major allergens it contains, Der p I or Der p II. Human eosinophils can, therefore, act as effective antigen-presenting cells to stimulate varied Th cell responses against a panel of antigens including HDM, TG or PPD, an ability that may help to determine the development of allergic disease. © 2016 John Wiley & Sons Ltd.

Enterobiliary Fistula as a Complication of Eosinophilic Gastroenteritis: a Case Report

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Kim, Han Myun; Woo, Ji Young [Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

2008-06-15

Eosinophilic gastroenteritis is an uncommon disease with variable clinical features characterized by eosinophilic infiltration. Clinical manifestations range from non-specific gastrointestinal complaints such as nausea, vomiting, crampy abdominal pain, and diarrhea to specific findings such as malabsorption, protein loosing enteropathy, luminal obstruction, eosinophilic ascites and effusion. We report here on a case of eosinophilic gastroenteritis causing enterobiliary fistula which is an extremely unusual complication

Enterobiliary Fistula as a Complication of Eosinophilic Gastroenteritis: a Case Report

International Nuclear Information System (INIS)

Kim, Han Myun; Woo, Ji Young

2008-01-01

Eosinophilic gastroenteritis is an uncommon disease with variable clinical features characterized by eosinophilic infiltration. Clinical manifestations range from non-specific gastrointestinal complaints such as nausea, vomiting, crampy abdominal pain, and diarrhea to specific findings such as malabsorption, protein loosing enteropathy, luminal obstruction, eosinophilic ascites and effusion. We report here on a case of eosinophilic gastroenteritis causing enterobiliary fistula which is an extremely unusual complication

Re-defining the Unique Roles for Eosinophils in Allergic Respiratory Inflammation

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Jacobsen, Elizabeth A.; Lee, Nancy A.; Lee, James J.

2014-01-01

Summary The role of eosinophils in the progression and resolution of allergic respiratory inflammation is poorly defined despite the commonality of their presence and in some cases their use as a biomarker for disease severity and/or symptom control. However, this ambiguity belies the wealth of insights that have recently been gained through the use of eosinophil-deficient/attenuated strains of mice that have demonstrated novel immunoregulatory and remodeling/repair functions for these cells in the lung following allergen provocation. Specifically, studies of eosinophil-deficient mice suggest that eosinophils contribute to events occurring in the lungs following allergen provocation at several key moments: (i) The initiating phase of events leading to Th2-polarized pulmonary inflammation, (ii) The suppression Th1/Th17 pathways in lung draining lymph nodes, (iii) The recruitment of effector Th2 T cells to the lung, and finally (iv) Mechanisms of inflammatory resolution that re-establish pulmonary homeostasis. These suggested functions have recently been confirmed and expanded upon using allergen provocation of an inducible eosinophil-deficient strain of mice (iPHIL) that demonstrated an eosinophil-dependent mechanism(s) leading to Th2 dominated immune responses in the presence of eosinophils in contrast to neutrophilic as well as mixed Th1/Th17/Th2 variant phenotypes in the absence of eosinophils. These findings highlighted that eosinophils are not exclusively downstream mediators controlled by T cells, dendritic cells (DC), and/or innate lymphocytic cells (ILC2). Instead, eosinophils appear to be more aptly described as significant contributors in complex interrelated pathways that lead to pulmonary inflammation and subsequently promote resolution and the re-establishment of homeostatic baseline. In this review we summarize and put into the context the evolving hypotheses that are now expanding our understanding of the roles eosinophils likely have in the lung

Eosinophilic granulomatosis with polyangiitis: an overview

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Andrea eGioffredi

2014-11-01

Full Text Available Eosinophilic granulomatosis with polyangiitis (EGPA is a multisystemic disorder, belonging to the small vessel ANCA-associated vasculitis, defined as a eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract, and necrotizing vasculitis predominantly affecting small to medium-sized vessels, associated with asthma and eosinophilia. EGPA pathogenesis is not well known: HLA-DRB1*04 and *07, HLA-DRB4 and IL10.2 haplotype of the IL-10 promoter gene are the most studied genetic determinants. Among the acquired pathogenetic factors, the exposure to different allergens, infections, vaccinations, drugs and silica exposure have been involved.Eosinophils are the most characteristic cells in EGPA and different studies have demonstrated their role as effector and immunoregulatory cells.EGPA is considered a disease with a prevalent activation of the Th2 cellular-mediated inflammatory response but also humoral immunity plays an important role. A link between B and T inflammatory responses may explain different disease features. EGPA typically develops into three sequential phases: the allergic phase, distinguished by the occurrence of asthma, allergic rhinitis and sinusitis, the eosinophilic phase, in which the main pathological finding is the eosinophilic organ infiltrations (e.g. lungs, heart and gastrointestinal system and the vasculitic phase, characterized by purpura, peripheral neuropathy and constitutional symptoms.ANCA (especially pANCA anti-MPO are present in 40-60% of the patients. An elevation of IgG4 is frequently found. Corticosteroids and cyclophosphamide are classically used for remission induction, while azathioprine and methotrexate are the therapeutic options for remission maintenance. B-cell depletion with rituximab has shown promising results for remission induction.

Eosinophilic Gastrointestinal Disorder in Coeliac Disease: A Case Report and Review

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Dennis N. F. Lim

2012-01-01

Full Text Available Eosinophilic gastrointestinal disorder is a rare disorder characterised by eosinophilic infiltration of the gastrointestinal tract. There are various gastrointestinal manifestations with eosinophilic ascites being the most unusual and rare presentation. Diagnosis requires high index of suspicion and exclusion of various disorders associated with peripheral eosinophilia. There are no previous case reports to suggest an association between eosinophilic gastrointestinal disorder and coeliac disease in adults. We report a case of eosinophilic ascites and gastroenteritis in a 30-year-old woman with a known history of coeliac disease who responded dramatically to a course of steroids.

Eosinophilic Pleural Effusion: A Rare Manifestation of Hypereosinophilic Syndrome

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Ndubuisi C. Okafor

2009-01-01

Full Text Available Several causes of eosinophilic pleural effusions have been described with malignancy being the commonest cause. Hypereosinophilic syndrome (HES is a rare disease and very few cases have been reported of HES presenting as eosinophilic pleural effusion (EPE. We report a case of a 26-year-old male who presented with shortness of breath. He had bilateral pleural effusions, generalized lymphadenopathy, splenomegaly, and leukocytosis with marked peripheral blood eosinophilia. The pleural fluid was exudative, with 25%–30% eosinophilis, and absence of neoplastic cells. Hypereosinophilic syndrome was diagnosed after other causes of eosinophilia were excluded. He continued to be dyspneic with persistent accumulation of eosinophilic pleural fluid, even after his peripheral eosinophil count had normalized in response to treatment. This patient represents a very unusual presentation of HES with dyspnea and pleural effusions and demonstrates that treatment based on response of peripheral eosinophil counts, as is currently recommended, may not always be clinically adequate.

Leukotriene B4 receptors on guinea pig alveolar eosinophils

International Nuclear Information System (INIS)

Maghni, K.; de Brum-Fernandes, A.J.; Foeldes-Filep, E.G.; Gaudry, M.; Borgeat, P.; Sirois, P.

1991-01-01

The existence of receptors for LTB4 on highly purified guinea pig alveolar eosinophils was investigated. Massive infiltration of eosinophils in alveolar spaces was induced in guinea pigs by i.v. injections of Sephadex beads G50 (16 mg/kg). Alveolar eosinophils (50 x 10(6) cells) were purified to approximately 98% by Percoll continuous density gradient centrifugation. The binding studies indicated that alveolar eosinophils bind LTB4 in a saturable, reversible and specific manner. Scatchard analysis indicated the existence of high-affinity binding sites (Kd1 = 1.00 ± 0.22 nM; Bmax1 = 966 ± 266 sites/cell) and low-affinity binding sites (Kd2 = 62.5 ± 8.9 nM; Bmax2 = 5557 ± 757 sites/cell). The metabolism of LTB4 by alveolar eosinophils in binding conditions was assessed by RP-HPLC and no significant degradation of [3H]LTB4 was observed. LTB4 dose-dependently stimulated eosinophil migration in both chemokinesis and chemotaxis assays with an EC50 value of 1.30 ± 0.14 and 18.14 ± 1.57 nM, respectively. LTB4 caused a dose-dependent increase in the production of superoxide anion with an apparent EC50 value of 50 x 10(-9) M in the authors experimental conditions. LTB4 also induced a dose-dependent increase in the generation of TxA2 with an EC50 value of 46.2 x 10(-9) M. Taken together, their results demonstrated that guinea pig alveolar eosinophils express two classes of specific receptors for LTB4. The high-affinity binding sites seem associated to chemokinesis and chemotaxis whereas the low-affinity binding sites seem associated to superoxide anion production and generation of TxA2. The existence of LTB4 receptors in eosinophils could explain the presence of these cells in hypersensitivity reactions

T-Cell lymphoproliferative disorder of hand-mirror cell morphology presenting in an eosinophilic loculated peritoneal effusion, with omental "caking"

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Tufankjian Dearon

2006-01-01

Full Text Available Abstract Background Cells with "hand mirror" morphology have not, to the best of our knowledge, been described in a primary effusion sample. This paper describes a case of T-cell lymphoma with eosinophilia in a patient with suspected peritoneal carcinomatosis. Rarely, a T-cell lymphoproliferative process may mimic primary peritoneal carcinomatosis, clinically suggested by a presentation in CT imaging of omental caking with bilateral massive loculated effusions in a patient without lymphadenopathy or splenomegaly. Methods A 60 year old caucasian male presented with vague abdominal discomfort and increasing abdominal girth. Computed tomography showed a two centimeter thick omental cake and a small loculated effusion. The clinical presentation and imaging findings were most consistent with peritoneal carcinomatosis. Cytologic evaluation of the effusion was undertaken for diagnostic study. Results Rapid intraprocedural interpretation of the effusion sample showed a monomorphic population of cells with "hand-mirror" cell morphology exhibiting cytoplasmic extensions (uropodia with 3–5 course dark cytoplasmic granules and a rim of vacuolated cytoplasm capping the opposing "mirror head" side. These cells were seen within a background of mature eosinophils. Flow cytometric evaluation of the ascites fluid demonstrated an atypical T-cell population with the following immunophenotype: CD2-, CD3+, CD4-, CD5-, CD7-, CD8+, CD56+. T-cell receptor (TCR gene rearrangement was positive for clonal TCR-gamma gene rearrangement, supporting the diagnosis of a T-lymphoprolifereative disorder. Conclusion A T-cell lymphoproliferative process may present with "hand mirror" morphology in an effusion sample. These cells may show polar cytoplasmic vacuolization and 3–5 course granules within the "handle" of these unique cells. Cytoplasm shows peripheral constriction around the nucleus.

Proton channel HVCN1 is required for effector functions of mouse eosinophils

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2013-01-01

Background Proton currents are required for optimal respiratory burst in phagocytes. Recently, HVCN1 was identified as the molecule required for the voltage-gated proton channel activity associated with the respiratory burst in neutrophils. Although there are similarities between eosinophils and neutrophils regarding their mechanism for respiratory burst, the role of proton channels in eosinophil functions has not been fully understood. Results In the present study, we first identified the expression of the proton channel HVCN1 in mouse eosinophils. Furthermore, using HVCN1-deficient eosinophils, we demonstrated important cell-specific effector functions for HVCN1. Similar to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils produced significantly less reactive oxygen species (ROS) upon phorbol myristate acetate (PMA) stimulation compared with WT eosinophils. In contrast to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils did not show impaired calcium mobilization or migration ability compared with wild-type (WT) cells. Uniquely, HVCN1-deficient eosinophils underwent significantly increased cell death induced by PMA stimulation compared with WT eosinophils. The increased cell death was dependent on NADPH oxidase activation, and correlated with the failure of HVCN1-deficient cells to maintain membrane polarization and intracellular pH in the physiological range upon activation. Conclusions Eosinophils require proton channel HVCN1 for optimal ROS generation and prevention of activation-induced cell death. PMID:23705768

A Non-Frequently Considered Diagnosis of Dysphagia; Eosinophilic Esophagitis

OpenAIRE

Mehmet Ağın; Nilgün Uyduran Ünal; Serdar İskit

2015-01-01

Eosinophilic Esophagitis is infiltration of esophagus mucosa by eosinophil leucocyte. It is rarely observed in children and the symptoms are similar to gastroesophageal reflux. This case, which was applied esophagus balloon dilatation in the pediatric surgery due to dysphagia and diagnosed eosinophilic esophagitis, was presented in order to attract attention to the approach to the child with dysphagia. Total IgE=834 IU/mL and specific IgE (-), Fx5 (-) was found negative. In ...

Increased eosinophil activity in acute Plasmodium falciparum infection - association with cerebral malaria

DEFF Research Database (Denmark)

Kurtzhals, J A; Reimert, C M; Tette, E

1998-01-01

To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven...... of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness...... followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM...

Eosinophilic esophagitis: an Italian experience Esofagitis eosinofílica: una experiencia italiana

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C. Vindigni

2010-01-01

Full Text Available Background: eosinophilic esophagitis is an esophageal disorder characterized by esophageal and/or upper gastrointestinal tract symptoms, and by dense esophageal eosinophilia associated with a normal gastric and duodenal mucosa. Prevalently reported in children, eosinophilic esophagitis has recently been reported with increased frequency also in adults. Aims: the purpose of this study was to report our experience with eosinophilic esophagitis in Italy, since there are only very few series of such patients in our country. Patients and methods: we retrospectively reviewed the histological data of consecutive patients with a diagnosis of esophagitis or reflux disease in the period September 2004-September 2008. Eosinophils were counted where they appeared most numerous in the biopsy, with a cutoff > 15 eosinophils in more than one high-power field as diagnostic of eosinophilic esophagitis. Patients were excluded if gastric or duodenal biopsies showed a prominent eosinophilic infiltrate. Results: twenty two patients (14 adults, 8 children, age range 2-59 years were identified according to the above criteria. The average eosinophil count was 86/ high-power field (range 31-150, associated with other pathologic features (eosinophilic microabscesses eosinophil degranulation, basal zone hyperplasia, papillary elongation. The main clinical complaints were dysphagia, food impaction, and heartburn, and endoscopic findings consisted of mucosal thickening and inelasticity, longitudinal shearing, rings, and white specks, without difference between adults and children for both clinical and endoscopic variables. Conclusions: eosinophilic esophagitis is not rare in Italy, and displays clinical, endoscopic, and pathologic features similar to those described in other countries.

Topical corticosteroids do not revert the activated phenotype of eosinophils in eosinophilic esophagitis but decrease surface levels of CD18 resulting in diminished adherence to ICAM-1, ICAM-2, and endothelial cells.

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Lingblom, Christine; Bergquist, Henrik; Johnsson, Marianne; Sundström, Patrik; Quiding-Järbrink, Marianne; Bove, Mogens; Wennerås, Christine

2014-12-01

Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

Eosinophilic granuloma of the mandibular condyle

International Nuclear Information System (INIS)

Huh, Kyung Hoe; Yi, Won Jin; Oh, Sung Won; Lee, Sam Sun; Choi, Mun Kyung

2008-01-01

The present study reports a case of eosinophilic granuloma of the mandibular condyle. Eosinophilic granulomas on the mandibular condyle are very rare, but there are several common clinical and radiographic presentations. The clinical presentations involve swelling on preauricular area, limitation of opening, TMJ pain, etc. The radiographic presentations involve radiolucent lytic condylar lesion with or without pathologic fracture. Sometimes new bone formations are observed. The purpose of the article is to add new cases to the literatures.

Eosinophilic granuloma of the mandibular condyle

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Huh, Kyung Hoe; Yi, Won Jin; Oh, Sung Won; Lee, Sam Sun [Department of Oral and Maxillofacial Radiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Choi, Mun Kyung [Department of Oral and Maxillofacial Surgery, College of Medicine, Inje University Sanggye Paik Hospital, Seoul (Korea, Republic of)

2008-03-15

The present study reports a case of eosinophilic granuloma of the mandibular condyle. Eosinophilic granulomas on the mandibular condyle are very rare, but there are several common clinical and radiographic presentations. The clinical presentations involve swelling on preauricular area, limitation of opening, TMJ pain, etc. The radiographic presentations involve radiolucent lytic condylar lesion with or without pathologic fracture. Sometimes new bone formations are observed. The purpose of the article is to add new cases to the literatures.

Eosinophilic cystitis in a 3-year-old boy

International Nuclear Information System (INIS)

Breysem, L.; Smet, M.H.; Gordts, H.; Marchal, G.

1991-01-01

Eosinophilic cystitis is a rare in children; it also affects adults. Clinical manifestations are variable. The diagnosis can be confirmed by cystoscopy and biopsy, both rather invasive procedures, especially in younger patients. We report a 3-year-old boy with eosinophilic cystitis. The most important radiological finding was marked thickening of the bladder wall, documented on ultrasound, cystography and CT. The CT findings of eosinophilic cystitis have, to the best of our knowledge, not been reported before. In addition to ultrasound and cystography, CT clearly demonstrates extension of the inflammatory process into the perivesical tissues. (orig.)

Eosinophilic Myocarditis due to Toxocariasis: Not a Rare Cause

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Shunichi Shibazaki

2016-01-01

Full Text Available 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.

Detection of eosinophil cationic protein (ECP) by an enzyme-linked immunosorbent assay

DEFF Research Database (Denmark)

Reimert, C M; Venge, P; Kharazmi, A

1991-01-01

Eosinophil cationic protein (ECP) is a highly basic and potent cytotoxic single-chain zinc-containing protein present in the granules of the eosinophilic granulocytes. ECP appears to be involved in defence against parasites and in the tissue damage seen in subjects with allergic and inflammatory...... disease. To investigate ECP release from in vitro activated human eosinophils and to study the involvement of eosinophils in health and disease, we have developed a sensitive and specific enzyme immunoassay. ECP was purified from normal human peripheral blood eosinophils and polyclonal antibodies to ECP...

In vivo activation of equine eosinophils and neutrophils by experimental Strongylus vulgaris infections.

Science.gov (United States)

Dennis, V A; Klei, T R; Chapman, M R; Jeffers, G W

1988-12-01

Eosinophils and neutrophils from ponies with Strongylus vulgaris-induced eosinophilia (eosinophilic ponies; activated eosinophils and neutrophils) were assayed in vitro for chemotactic and chemokinetic responses to zymosan-activated serum (ZAS) using the filter system in Boyden chambers, for Fc and complement (C) receptors using the EA and EAC-rosette assays, respectively, and for phagocytic and bactericidal activities using opsonized Escherichia coli and the acridine orange method. The responses of activated eosinophils and neutrophils in the above assays were compared with those of eosinophils and neutrophils from S. vulgaris-naive ponies without eosinophilia (noneosinophilic ponies; nonactivated eosinophils and neutrophils). Differences in cell density following centrifugation in a continuous Percoll gradient were used to further characterize the heterogeneity of activated eosinophils and neutrophils. Activated and nonactivated eosinophils demonstrated similar chemotactic responses to ZAS while activated and nonactivated neutrophils demonstrated similar chemokinetic responses to ZAS. A higher percentage of activated eosinophils and neutrophils expressed Fc and C receptors compared with nonactivated cells (P less than 0.05). Generally, higher percentages of eosinophils and neutrophils expressed C than Fc receptors. However, the percentage of neutrophils with both receptors was higher than that of eosinophils. Phagocytosis and killing of E. coli by either type of eosinophil were not consistently observed. Both activated and nonactivated neutrophils phagocytized E. coli and significant differences between the two cell types were not observed. The bacterial activity, however, of activated neutrophils was significantly greater than that obtained using nonactivated neutrophils (P less than 0.05). Activated eosinophils and neutrophils were both separated into two distinct fractions based on differences in cell densities. A higher percentage of band 2 eosinophils

Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis

Science.gov (United States)

Griseri, Thibault; Arnold, Isabelle C.; Pearson, Claire; Krausgruber, Thomas; Schiering, Chris; Franchini, Fanny; Schulthess, Julie; McKenzie, Brent S.; Crocker, Paul R.; Powrie, Fiona

2015-01-01

Summary The role of intestinal eosinophils in immune homeostasis is enigmatic and the molecular signals that drive them from protective to tissue damaging are unknown. Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal inflammation was characterized by increased bone marrow eosinopoiesis and accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil depletion ameliorated colitis, implicating eosinophils in disease pathogenesis. GM-CSF was a potent activator of eosinophil effector functions and intestinal accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast neutrophil accumulation was GM-CSF independent and dispensable for colitis. In addition to TNF secretion, release of eosinophil peroxidase promoted colitis identifying direct tissue-toxic mechanisms. Thus, eosinophils are key perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic target. PMID:26200014

Eosinophilic pleural effusion: incidence, etiology and prognostic significance.

Science.gov (United States)

Ferreiro, Lucía; San José, Esther; González-Barcala, Francisco Javier; Alvarez-Dobaño, José Manuel; Golpe, Antonio; Gude, Francisco; Anchorena, Christian; Pereyra, Marco F; Zamarrón, Carlos; Valdés, Luis

2011-10-01

Eosinophilic pleural effusion (EPE) has been associated with less risk for malignancy with a potential causal relationship with the presence of air and/or blood in the pleural space. However, these theories have fallen by the wayside in the light of recent publications. To determine the incidence and etiology of EPE and to observe whether the eosinophils in the pleural liquid (PL) increase in successive thoracocenteses. We analyzed 730 PL samples from 605 patients hospitalized between January 2004 and December 2010. We identified 55 samples with EPE from 50 patients (8.3%). The most frequent etiologies of EPE were: unknown (36%) and neoplasm (30%). There were no significant differences in the incidence of neoplasms between the non-eosinophilic pleural effusions (non-EPE) (25.9%) and the EPE (30%) (p=0.533). One hundred patients (16.5%) underwent a second thoracocentesis. Out of the 9 who had EPE in the first, 6 maintained EPE in the second. Out of the 91 with non-EPE in the first thoracocentesis, 8 (8.8%) had EPE in the repeat thoracocentesis. The percentage of eosinophils did not increase in the successive thoracocenteses (p=0.427). In the EPE, a significant correlation was found between the number of hematites and eosinophils in the PL (r=0.563; p=0.000). An EPE cannot be considered an indicator of benignancy, therefore it should be studied as any other pleural effusion. The number of eosinophils does not seem to increase with the of repetition of thoracocentesis and, lastly, the presence of blood in the PL could explain the existence of EPE. Copyright © 2011 SEPAR. Published by Elsevier Espana. All rights reserved.

EOSINOPHILIC INFLAMMATORY DISEASES OF THE GASTROINTESTINAL TRACT AND FOOD ALLERGY AMONG CHILDREN

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P.V. Shumilov

2007-01-01

Full Text Available Within the structure of the inflammatory diseases of the gastrointestinal tract among children, one may single out a specific group of the chronic pathology of the digestive apparatus — eosinophilic diseases of the gastrointestinal tract and gastroenterological manifestations of the food allergy. The food allergy is characterized by the pathologic immune reactivity among commonly genetically predisposed people. Depending on the peculiarities of the immune reactivity of a sick person and the nature of the allergen, the allergic reaction may evolve with primary involvement of the different mechanisms or th2 IgE-mediated, or Th1 non-igecmediated. Clinical picture of the food allergy is the manifestation of the immunoinflammatory process caused by the interaction of the food antigens with the structures of the lymphoid tissues associated with the mucous membranes of this or that target organ. The morphological basis of the clinical picture is mostly immune inflammation with primarily eosinophilic tissue infiltration. The eosinophilic lesions of the gastrointestinal tract include eosinophilic esophagitis, eosinophilic gastroenteritis, eosinophilic enteritis, eosinophilic colitis, eosinophilic proctitis and other states. During the food allergy each of the clinical forms of the gastrointestinal tract lesion has its own peculiarities with regards to the primary development mechanism, age of manifestation, character of the run and behaviour tactics.Key words: eosinophilic inflammation, esophagitis, gastroenteritis, colitis, food allergy.

Genetics of eosinophilic esophagitis.

Science.gov (United States)

Kottyan, L C; Rothenberg, M E

2017-05-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches.

Proteins contribute insignificantly to the intrinsic buffering capacity of yeast cytoplasm

International Nuclear Information System (INIS)

Poznanski, Jaroslaw; Szczesny, Pawel; Ruszczyńska, Katarzyna; Zielenkiewicz, Piotr; Paczek, Leszek

2013-01-01

Highlights: ► We predicted buffering capacity of yeast proteome from protein abundance data. ► We measured total buffering capacity of yeast cytoplasm. ► We showed that proteins contribute insignificantly to buffering capacity. -- Abstract: Intracellular pH is maintained by a combination of the passive buffering of cytoplasmic dissociable compounds and several active systems. Over the years, a large portion of and possibly most of the cell’s intrinsic (i.e., passive non-bicarbonate) buffering effect was attributed to proteins, both in higher organisms and in yeast. This attribution was not surprising, given that the concentration of proteins with multiple protonable/deprotonable groups in the cell exceeds the concentration of free protons by a few orders of magnitude. Using data from both high-throughput experiments and in vitro laboratory experiments, we tested this concept. We assessed the buffering capacity of the yeast proteome using protein abundance data and compared it to our own titration of yeast cytoplasm. We showed that the protein contribution is less than 1% of the total intracellular buffering capacity. As confirmed with NMR measurements, inorganic phosphates play a crucial role in the process. These findings also shed a new light on the role of proteomes in maintaining intracellular pH. The contribution of proteins to the intrinsic buffering capacity is negligible, and proteins might act only as a recipient of signals for changes in pH.

Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

DEFF Research Database (Denmark)

Withers, Sarah B.; Forman, Ruth; Meza-Perez, Selene

2017-01-01

Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils...... in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability...... of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source...

Eosinophilic cholecystitis: an infrequent cause of acute cholecystitis

Directory of Open Access Journals (Sweden)

María del Moral-Martínez

2015-01-01

Full Text Available Eosinophilic cholecystitis (EC is a rare disease that is characterised by eosinophilic infiltration of the gallbladder. Its pathogenesis is unknown, although many hypotheses have been made. Clinical and laboratory manifestations do not differ from those of other causes of cholecystitis. Diagnosis is histological and usually performed after analysis of the surgical specimen. We report the case of a woman aged 24 years, with symptoms of fever, vomiting and pain in the right upper quadrant. When imaging tests revealed acalculous cholecystitis, an urgent cholecystectomy was performed. Histological examination of the surgical specimen revealed eosinophilic cholecystitis. No cause of the symptoms was found.

Eosinophil count is positively correlated with coronary artery calcification

International Nuclear Information System (INIS)

Tanaka, Muhei; Fukui, Michiaki; Yamasaki, Masahiro; Hasegawa, Goji; Oda, Yohei; Nakamura, Naoto; Tomiyasu, Ki-ichiro; Akabame, Satoshi; Nakano, Koji

2012-01-01

Recent studies suggested that allergic disorders and increased eosinophil count were associated with atherosclerosis. The purpose of this study was to assess the relationship between eosinophil count and coronary artery calcification (CAC). We performed a cross-sectional study in 1363 consecutive participants with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAC score determined by multislice CT and peripheral eosinophil count as well as major cardiovascular risk factors, including age, body mass index, smoking status, hypertension, dyslipidemia, diabetes mellitus (DM), high-sensitivity C-reactive protein and estimated glomerular filtration rate (eGFR). Sex (P=0.0004), hypertension (P=0.0002), dyslipidemia (P=0.0004) and DM (P=0.0061) were associated with log (CAC+1), respectively. Positive correlations were found between log (CAC+1), and age (r=0.325, P<0.0001) and eosinophil count (r=0.165, P<0.0001). Negative correlations were found between log (CAC+1) and eGFR (r=-0.166, P<0.0001). Multivariate linear regression analysis demonstrated that age (β=0.314, P<0.0001), sex (β=0.124, P<0.0001), hypertension (β=0.084, P=0.0008), DM (β=0.108, P<0.0001), eGFR (β=-0.079, P=0.0021) and eosinophil count (β=0.147, P<0.0001) were independent determinants of log (CAC+1). In conclusion, eosinophil count correlated positively with CAC in participants with clinical suspicion of CHD. (author)

Eosinophilic granuloma in the anterior mandible mimicking radicular cyst

International Nuclear Information System (INIS)

Lee, Byung Do; Lee, Wan; Lee, Jun; Son, Hyun Jin

2013-01-01

Eosinophilic granuloma is a common expression of Langerhans cell histiocytosis and corresponds with typical bone lesions. The radiographic appearance of eosinophilic granuloma in the jaw is variable and not specific. It may resemble periodontitis, radicular cyst, or malignancies. The purpose of this report is to describe the characteristic radiographic features of eosinophilic granuloma of a 39-year-old male. The lesion in the anterior mandible was first diagnosed as radicular cyst because the radiographic findings were ovoid radiolucent lesion with well-defined border. However, careful interpretation revealed a non-corticated border and floating tooth appearance that were the characteristic radiographic features for the differential diagnosis. Early clinical signs of eosinophilic granuloma can occur in the jaw and a bony destructive lesion might be mistaken for periodontitis or an odontogenic cystic lesion; therefore, careful interpretation of radiographs should be emphasized.

Eosinophilic granuloma in the anterior mandible mimicking radicular cyst

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Lee, Byung Do; Lee, Wan; Lee, Jun [College of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Son, Hyun Jin [Dept. of Pathology, School of Medicine, Eulji University, Daejeon (Korea, Republic of)

2013-06-15

Eosinophilic granuloma is a common expression of Langerhans cell histiocytosis and corresponds with typical bone lesions. The radiographic appearance of eosinophilic granuloma in the jaw is variable and not specific. It may resemble periodontitis, radicular cyst, or malignancies. The purpose of this report is to describe the characteristic radiographic features of eosinophilic granuloma of a 39-year-old male. The lesion in the anterior mandible was first diagnosed as radicular cyst because the radiographic findings were ovoid radiolucent lesion with well-defined border. However, careful interpretation revealed a non-corticated border and floating tooth appearance that were the characteristic radiographic features for the differential diagnosis. Early clinical signs of eosinophilic granuloma can occur in the jaw and a bony destructive lesion might be mistaken for periodontitis or an odontogenic cystic lesion; therefore, careful interpretation of radiographs should be emphasized.

Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response.

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Muniz, Valdirene S; Baptista-Dos-Reis, Renata; Benjamim, Claudia F; Mata-Santos, Hilton A; Pyrrho, Alexandre S; Strauch, Marcelo A; Melo, Paulo A; Vicentino, Amanda R R; Silva-Paiva, Juliana; Bandeira-Melo, Christianne; Weller, Peter F; Figueiredo, Rodrigo T; Neves, Josiane S

2015-01-01

Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S. mansoni) infection. We found that adenosine 5'-diphosphate (ADP) induced human eosinophils to secrete eosinophil peroxidase (EPO) in a P2Y12R dependent manner. However, ADP did not interfere with human eosinophil apoptosis or chemotaxis in vitro. In vivo, C57Bl/6 mice were infected with cercariae of the Belo Horizonte strain of S. mansoni. Analyses performed 55 days post infection revealed that P2Y12R blockade reduced the granulomatous hepatic area and the eosinophilic infiltrate, collagen deposition and IL-13/IL-4 production in the liver without affecting the parasite oviposition. As found for humans, murine eosinophils also express the P2Y12R. P2Y12R inhibition increased blood eosinophilia, whereas it decreased the bone marrow eosinophil count. Our results suggest that P2Y12R has an important role in eosinophil EPO secretion and in establishing the inflammatory response in the course of a S. mansoni infection.

Characterization of cytoplasmic male sterility of rice with Lead Rice cytoplasm in comparison with that with Chinsurah Boro II cytoplasm.

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Itabashi, Etsuko; Kazama, Tomohiko; Toriyama, Kinya

2009-02-01

Rice with LD-type cytoplasmic male sterility (CMS) possesses the cytoplasm of 'Lead Rice' and its fertility is recovered by a nuclear fertility restorer gene Rf1. Rf1 promotes processing of a CMS-associated mitochondrial RNA of atp6-orf79, which consists of atp6 and orf79, in BT-CMS with the cytoplasm of 'Chinsurah Boro II'. In this study, we found that LD-cytoplasm contained a sequence variant of orf79 downstream of atp6. Northern blot analysis showed that atp6-orf79 RNA of LD-cytoplasm was co-transcribed and was processed in the presence of Rf1 in the same manner as in BT-cytoplasm. Western blot analysis showed that the ORF79 peptide did not accumulate in an LD-CMS line, while ORF79 accumulated in a BT-CMS line and was diminished by Rf1. These results suggest that accumulation of ORF79 is not the cause of CMS in LD-cytoplasm and the mechanism of male-sterility induction/fertility restoration in LD-CMS is different from that in BT-CMS.

Eosinophilic Esophagitis (EoE)

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... excluded usually include dairy, egg, wheat, soy, peanut, tree nuts and fish/shellfish. These diets have been ... minorities » IgE ab to minor milk proteins may identify the proteins that are relevant to eosinophilic esophagitis » ...

Diagnosis and classification of eosinophilic granulomatosis with polyangiitis (formerly named Churg-Strauss syndrome).

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Mouthon, Luc; Dunogue, Bertrand; Guillevin, Loïc

2014-01-01

Recently, a group of experts in the field suggested to rename Churg-Strauss syndrome as eosinophilic granulomatosis with polyangiitis (EGPA). This condition, first described in 1951, is a rare small- and medium-sized-vessel vasculitis characterized by an almost constant association with asthma and eosinophilia, and, by the presence of anti-myeloperoxidase (MPO) antineutrophil cytoplasm antibodies (ANCA) in 30-38% of the patients. Vasculitis typically develops in a previously asthmatic and eosinophilic middle-aged patient. Asthma is severe, associated with eosinophilia and extrapulmonary symptoms. Most frequently EGPA involves the peripheral nerves and skin. Other organs, however, may be affected and must be screened for vasculitis, especially those associated with a poorer prognosis, such as the heart, kidney and gastrointestinal tract, as assessed by the recently revised Five-Factor Score (FFS). Recent insights, particularly concerning clinical differences associated with ANCA status, showed that EGPA patients might constitute a heterogeneous group. Thus, EGPA patients with anti-MPO ANCA suffered more, albeit not exclusively, from vasculitis symptoms, such as glomerulonephritis, mononeuritis multiplex and alveolar hemorrhage, whereas ANCA-negative patients more frequently develop heart involvement. This observation led to the hypothesis that EGPA might be divided into different clinical and pathophysiological subtypes, which could be managed better with more specifically adapted therapies. For now, EGPA treatment still relies mainly on corticosteroids and, when necessary for patients with poorer prognoses, combined immunosuppressant drugs, especially cyclophosphamide. Overall survival of EGPA patients is good, despite not uncommon relapses. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pediatric eosinophilic esophagitis: radiologic findings with pathologic correlation

International Nuclear Information System (INIS)

Binkovitz, Larry A.; Lorenz, Emily A.; Di Lorenzo, Carlo; Kahwash, Samir

2010-01-01

Eosinophilic esophagitis is increasingly recognized as a cause of dysphagia or food impaction in pediatric patients. It has a high male predominance and is often associated with a history of allergy or asthma. To correlate fluoroscopic findings in eosinophilic esophagitis with the endoscopic and histologic findings. We retrospectively reviewed the upper gastrointestinal (UGI) findings of eosinophilic esophagitis and correlated them with the clinical, endoscopic and histologic findings in a series of 17 children (12 boys, 5 girls). UGI findings were normal in 12 children, including 4 who had a normal UGI exam after endoscopic disimpaction for an obstructing food bolus. Five children had strictures identified on UGI: one was demonstrated with endoscopy. This suggests that the impactions and strictures were due to an esophageal dysmotility rather than a fixed anatomic abnormality. Because the UGI findings are frequently normal in eosinophilic esophagitis, radiologists need to have a high index of suspicion for this disease. In children with a strong clinical history, especially impaction in the absence of an esophageal stricture, endoscopy and biopsy are indicated for further evaluation. (orig.)

Pediatric eosinophilic esophagitis: radiologic findings with pathologic correlation

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Binkovitz, Larry A. [Nationwide Children' s Hospital, Columbus, OH (United States); Mayo Clinic, Division of Pediatric Radiology, E-2, Rochester, MN (United States); Lorenz, Emily A. [Nationwide Children' s Hospital, Columbus, OH (United States); Di Lorenzo, Carlo [Nationwide Children' s Hospital, Department of Gastroenterology, Columbus, OH (United States); Kahwash, Samir [Nationwide Children' s Hospital, Department of Pathology, Columbus, OH (United States)

2010-05-15

Eosinophilic esophagitis is increasingly recognized as a cause of dysphagia or food impaction in pediatric patients. It has a high male predominance and is often associated with a history of allergy or asthma. To correlate fluoroscopic findings in eosinophilic esophagitis with the endoscopic and histologic findings. We retrospectively reviewed the upper gastrointestinal (UGI) findings of eosinophilic esophagitis and correlated them with the clinical, endoscopic and histologic findings in a series of 17 children (12 boys, 5 girls). UGI findings were normal in 12 children, including 4 who had a normal UGI exam after endoscopic disimpaction for an obstructing food bolus. Five children had strictures identified on UGI: one was demonstrated with endoscopy. This suggests that the impactions and strictures were due to an esophageal dysmotility rather than a fixed anatomic abnormality. Because the UGI findings are frequently normal in eosinophilic esophagitis, radiologists need to have a high index of suspicion for this disease. In children with a strong clinical history, especially impaction in the absence of an esophageal stricture, endoscopy and biopsy are indicated for further evaluation. (orig.)

Dynamics of vegetative cytoplasm during generative cell formation and pollen maturation in Arabidopsis thaliana

Science.gov (United States)

Kuang, A.; Musgrave, M. E.

1996-01-01

Ultrastructural changes of pollen cytoplasm during generative cell formation and pollen maturation in Arabidopsis thaliana were studied. The pollen cytoplasm develops a complicated ultrastructure and changes dramatically during these stages. Lipid droplets increase after generative cell formation and their organization and distribution change with the developmental stage. Starch grains in amyloplasts increase in number and size during generative and sperm cell formation and decrease at pollen maturity. The shape and membrane system of mitochondria change only slightly. Dictyosomes become very prominent, and numerous associated vesicles are observed during and after sperm cell formation. Endoplasmic reticulum appears extensively as stacks during sperm cell formation. Free and polyribosomes are abundant in the cytoplasm at all developmental stages although they appear denser at certain stages and in some areas. In mature pollen, all organelles are randomly distributed throughout the vegetative cytoplasm and numerous small particles appear. Organization and distribution of storage substances and appearance of these small particles during generative and sperm cell formation and pollen maturation are discussed.

Esophageal motility in eosinophilic esophagitis.

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Weiss, A H; Iorio, N; Schey, R

2015-01-01

Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus and is a potential cause of dysphagia and food impaction, most commonly affecting young men. Esophageal manometry findings vary from normal motility to aperistalsis, simultaneous contractions, diffuse esophageal spasm, nutcracker esophagus or hypotonic lower esophageal sphincter (LES). It remains unclear whether esophageal dysmotility plays a significant role in the clinical symptoms of EoE. Our aim is to review the pathogenesis, diagnosis, and effect of treatment on esophageal dysmotility in EoE. A literature search utilizing the PubMed database was performed using keywords: eosinophilic esophagitis, esophageal dysmotility, motility, manometry, impedance planimetry, barium esophagogram, endoscopic ultrasound, and dysphagia. Fifteen studies, totaling 387 patients with eosinophilic esophagitis were identified as keeping in accordance with the aim of this study and included in this review. The occurrence of abnormal esophageal manometry was reported to be between 4 and 87% among patients with EoE. Esophageal motility studies have shown reduced distensibility, abnormal peristalsis, and hypotonicity of the LES in patients with EoE, which may also mimic other esophageal motility disorders such as achalasia or nutcracker esophagus. Studies have shown conflicting results regarding the presence of esophageal dysmotility and symptoms with some reports suggesting a higher rate of food impaction, while others report no correlation between motor function and dysphagia. Motility dysfunction of the esophagus in EoE has not been well reported in the literature and studies have reported conflicting evidence regarding the clinical significance of dysmotility seen in EoE. The correlation between esophageal dysmotility and symptoms of EoE remains unclear. Larger studies are needed to investigate the incidence of esophageal dysmotility, clinical implications, and effect of treatment on

A rare occurrence of a steroid cell tumor of the pelvic mesentery: a case report

OpenAIRE

Louis Robert; Murhekar Kanchan; Majhi Urmila

2011-01-01

Abstract Introduction Steroid cell tumors are microscopically characterized by abundant eosinophilic or vacuolated cytoplasm that is often positive for fat stains. These tumors could be of ovarian or ectopic adrenal origin. We present a rare case of a steroid cell tumor arising from the pelvic mesentery. Case presentation A 31-year-old Asian woman was undergoing treatment for infertility and virilizing symptoms. She underwent laparoscopy followed by laprotomy for a suspected ovarian cyst/pelv...

Total artificial heart implantation for biventricular failure due to eosinophilic myocarditis.

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Kawabori, Masashi; Kurihara, Chitaru; Miller, Yair; Heck, Kent A; Bogaev, Roberta C; Civitello, Andrew B; Cohn, William E; Frazier, O H; Morgan, Jeffrey A

2017-09-01

Idiopathic hypereosinophilic syndrome is a condition of unknown etiology characterized by proliferation of eosinophils and their infiltration into tissues. Although cardiac involvement is rare, eosinophilic myocarditis can lead to life-threating fulminant congestive heart failure. Treatment of patients with eosinophilic myocarditis is challenging as heart failure can be caused by biventricular dysfunction. To our knowledge, this is the first case reported in the literature describing a patient with acute severe biventricular heart failure caused by eosinophilic myocarditis with mural left ventricular apical thrombus who was successfully treated with implantation of a total artificial heart as a bridge to heart transplant.

Isolation of Eosinophils from the Lamina Propria of the Murine Small Intestine.

Science.gov (United States)

Berek, Claudia; Beller, Alexander; Chu, Van Trung

2016-01-01

Only recently has it become apparent that eosinophils play a crucial role in mucosal immune homeostasis. Although eosinophils are the main cellular component of the lamina propria of the gastrointestinal tract, they have often been overlooked because they express numerous markers, which are normally used to characterize macrophages and/or dendritic cells. To study their function in mucosal immunity, it is important to isolate them with high purity and viability. Here, we describe a protocol to purify eosinophils from the lamina propria of the murine small intestine. The method involves preparation of the small intestine, removal of epithelial cells and digestion of the lamina propria to release eosinophils. A protocol to sort eosinophils is included.

Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma

DEFF Research Database (Denmark)

Duong, MyLinh; Subbarao, Padmaja; Adelroth, Ellinor

2008-01-01

BACKGROUND: The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined. METHODS: Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double...... and sputum analysis were performed. RESULTS: Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated...... eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of eosinophilic groups in the magnitude of improvement in EIB was evident after the first...

Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease

DEFF Research Database (Denmark)

Vedel-Krogh, Signe; Nielsen, Sune F; Lange, Peter

2016-01-01

RATIONALE: Whether high blood eosinophils are associated with COPD exacerbations among individuals with COPD in the general population is largely unknown. OBJECTIVES: To test the hypothesis that high blood eosinophils predict COPD exacerbations. METHODS: Among 81,668 individuals from the Copenhagen...... General Population Study, we examined 7,225 with COPD based on spirometry. We recorded blood eosinophils at baseline and future COPD exacerbations longitudinally, defined as moderate (short-course treatment of systemic corticosteroids) or severe (hospitalization). We also assessed exacerbation risk...... in a subgroup of 203 COPD individuals with clinical COPD, defined as participants with ≥ 10 pack-years, FEV1

Eosinophilic Colitis: University of Minnesota Experience and Literature Review

Directory of Open Access Journals (Sweden)

Wolfgang B. Gaertner

2011-01-01

Full Text Available Eosinophilic colitis is a rare form of primary eosinophilic gastrointestinal disease that is poorly understood. Neonates and young adults are more frequently affected. Clinical presentation is highly variable depending on the depth of inflammatory response (mucosal, transmural, or serosal. The pathophysiology of eosinophilic colitis is unclear but is suspected to be related to a hypersensitivity reaction given its correlation with other atopic disorders and clinical response to corticosteroid therapy. Diagnosis is that of exclusion and differential diagnoses are many because colonic tissue eosinophilia may occur with other colitides (parasitic, drug-induced, inflammatory bowel disease, and various connective tissue disorders. Similar to other eosinophilic gastrointestinal disorders, steroid-based therapy and diet modification achieve very good and durable responses. In this paper, we present our experience with this rare pathology. Five patients (3 pediatric and 2 adults presented with diarrhea and hematochezia. Mean age at presentation was 26 years. Mean duration of symptoms before pathologic diagnosis was 8 months. Mean eosinophil count per patient was 31 per high-power field. The pediatric patients responded very well to dietary modifications, with no recurrences. The adult patients were treated with steroids and did not respond. Overall mean followup was 22 (range, 2–48 months.

Higher frequency of cholelithiasis in eosinophilic cholecystitis, an unusual finding

International Nuclear Information System (INIS)

Sarfraz, T.; Tariq, H.; Bashir, S.

2015-01-01

To determine the frequency of cholelithiasis in eosinophilic cholecystitis in our population. Study Design: Prospective descriptive study. Place and Duration of Study: Histopathology department, Combined Military Hospital (CMH), Peshawar (Pakistan) from Dec 2011 to Nov 2014. Material and Methods: Eighteen hundred (1800) cholecystectomy specimens were included in the study. The specimens which were properly fixed in 10% formalin were included in the specimen, while poorly fixed and autolysed specimens were excluded. The specimens were examined grossly, measured and block selection was done. The slides made were examined under light microscope by one histopathologist and findings were analyzed. Results: Out of 1800 cholecystectomy specimens, 25 cases (1.38%) were diagnosed as eosinophilic cholecystitis. Out of these 25 cases, 20 (80%) were females having an age range of 30-50 years, while 5 (20%) were males with an age range of 35-55 years. Out of these 25 cases of eosinophilic cholecystitis, 22 (88%) were having cholelithiasis, while 3 (12%) were acalculous eosiniophilic cholecystitis. Conclusion: Eosinophilic cholecystitis in our population is mostly calculous which is very significant finding contrary to data given in western literature, where most of eosinophilic cholecystitis is aclculous. This needs further evaluation to determine any genetic, geographic, environmental, dietary, microbiological or any other factor responsible in etiopathogenesis of calculous eosinophilic cholecystitis in our population, which could be helpful in prevention and management of this disease. (author)

Esophageal trachealization: A feature of eosinophilic esophagitis

International Nuclear Information System (INIS)

AlHussaini, Abdulrahman A; Semaan, Toufic; ElHag, Imad A

2009-01-01

Eosinophilic esophagitis (EE) is an inflammatory condition characterized by intense eosinophilic infiltration of the esophagus. EE is frequently misdiagnosed as gastroesophageal reflux disease. Here, we present a child with EE and a characteristic endoscopic finding, r inged esophagus . An 11-year-old Saudi boy presented with dysphagia for 1 year. He had experienced an intermittent sensation of solid food sticking in his chest, which was relieved by drinking liquids. A barium swallow excluded anatomical causes of dysphagia, but revealed multiple-ringed esophagus. Endoscopy showed a furrowing and trachealizing appearance of the entire esophagus. Hisologically, extensive eosinophilic infiltration was a feature in biopsies obtained from the esophagus. The child responded well to a 2-month course of inhaled fluticasone. Symptoms recurred 3 months after discontinuation of therapy, which necessitated resumption of inhaled fluticasone. The endoscopic appearance of multiple esophageal rings should raise suspicion of EE and be confirmed by esophageal biopsies. (author)

Point-of-care blood eosinophil count in a severe asthma clinic setting.

Science.gov (United States)

Heffler, Enrico; Terranova, Giovanni; Chessari, Carlo; Frazzetto, Valentina; Crimi, Claudia; Fichera, Silvia; Picardi, Giuseppe; Nicolosi, Giuliana; Porto, Morena; Intravaia, Rossella; Crimi, Nunzio

2017-07-01

One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers. A significant correlation between blood eosinophils assessed by the 2 devices was found (R 2  = 0.854, P asthma and the ELEN index, a composite score useful to predict sputum eosinophilia. The results of our study contribute to the validation of a point-of-care device to assess blood eosinophils and open the possibility of using this device for the management of severe asthma management. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Intestinal perforation in a two-year-old child with eosinophilic gastroenteritis

DEFF Research Database (Denmark)

Agertoft, A; Husby, S; Høst, A

1991-01-01

A two-year-old boy underwent a laparatomy for an intestinal perforation due to eosinophilic gastroenteritis. He had marked peripheral blood eosinophilia and a small duodenal biopsy showed heavy eosinophilic infiltration in the mucosa. After 1 1/2 year on a restricted diet, a control duodenal biopsy...... showed only slight eosinophilia. Perforation of the small intestine is a rare but serious complication in eosinophilic gastroenteritis....

Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

Science.gov (United States)

Thiel, Jens; Hässler, Fabian; Salzer, Ulrich; Voll, Reinhard E; Venhoff, Nils

2013-09-24

Eosinophilic granulomatosis with polyangiitis (EGPA) is part of antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitides. In EGPA small-vessel vasculitis is associated with eosinophilia and asthma. About 40% of EGPA patients are ANCA-positive, suggesting a role for B cells in the pathogenesis of EGPA. B cell-depleting therapy with rituximab (RTX) can be effective in ANCA-positive EGPA, but very few patients have been published to date. The role of RTX in the treatment of ANCA-negative EGPA is unclear. We report a single-center cohort of patients with eosinophilic granulomatosis with polyangiitis. Of these patients, nine (six ANCA-positive, three ANCA-negative) had been treated with RTX for relapsing or refractory disease on standard immunosuppressive treatment. In a retrospective analysis, data on treatment response, frequency of relapses, adverse events, and peripheral B-cell reconstitution were evaluated. Furthermore, serum immunoglobulin concentrations, ANCA status, and peripheral B cell subpopulations were assessed after RTX treatment. All patients had high disease activity before RTX treatment. At presentation 3 months after RTX therapy, all ANCA-positive and ANCA-negative patients had responded to RTX, with one patient being in complete remission, and eight patients being in partial remission. After a mean follow-up of 9 months, C-reactive protein concentrations had normalized, eosinophils had significantly decreased, and prednisone had been tapered in all patients. In all patients, RTX therapy was combined with a standard immunosuppressive therapy. Within the 9-month observation period, no relapse was recorded. Three patients were preemptively retreated with RTX, and during the median follow-up time of 3 years, no relapse occurred in these patients. During the follow-up of 13 patient-years, five minor but no major infections were recorded. In our analysis on nine patients with EGPA resistant to standard therapy, rituximab proved to be an

The Role and Immunobiology of Eosinophils in the Respiratory System: a Comprehensive Review.

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Eng, Stephanie S; DeFelice, Magee L

2016-04-01

The eosinophil is a fully delineated granulocyte that disseminates throughout the bloodstream to end-organs after complete maturation in the bone marrow. While the presence of eosinophils is not uncommon even in healthy individuals, these granulocytes play a central role in inflammation and allergic processes. Normally appearing in smaller numbers, higher levels of eosinophils in the peripheral blood or certain tissues typically signal a pathologic process. Eosinophils confer a beneficial effect on the host by enhancing immunity against molds and viruses. However, tissue-specific elevation of eosinophils, particularly in the respiratory system, can cause a variety of short-term symptoms and may lead to long-term sequelae. Eosinophils often play a role in more commonly encountered disease processes, such as asthma and allergic responses in the upper respiratory tract. They are also integral in the pathology of less common diseases including eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and drug reaction with eosinophilia and systemic symptoms. They can be seen in neoplastic disorders or occupational exposures as well. The involvement of eosinophils in pulmonary disease processes can affect the method of diagnosis and the selection of treatment modalities. By analyzing the complex interaction between the eosinophil and its environment, which includes signaling molecules and tissues, different therapies have been discovered and created in order to target disease processes at a cellular level. Innovative treatments such as mepolizumab and benralizumab will be discussed. The purpose of this article is to further explore the topic of eosinophilic presence, activity, and pathology in the respiratory tract, as well as discuss current and future treatment options through a detailed literature review.

IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells.

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Hashiguchi, Masaaki; Kashiwakura, Yuji; Kojima, Hidefumi; Kobayashi, Ayano; Kanno, Yumiko; Kobata, Tetsuji

2015-03-01

Eosinophils are multifunctional leukocytes involved in allergic reactions as well as adipose tissue regulation. IL-5 is required for eosinophil survival; however, the in vivo mechanisms of eosinophil regulation are not fully understood. A tg mouse model with il5 promoter-driven EGFP expression was established for detecting the IL-5-producing cells in vivo. Il5-egfp tg mice expressed high levels of EGFP in gonadal adipose tissue (GAT) cells. EGFP(+) cells in GAT were mainly group 2 innate lymphoid cells (ILCs). IL-33 preferentially expanded EGFP(+) cells and eosinophils in GAT in vivo. EGFP(+) ILCs were found to upregulate prg2 mRNA expression in GAT eosinophils. These results demonstrate that ILCs activate eosinophils in GAT. The blockage of IL-33Rα, on the other hand, did not impair EGFP(+) ILC numbers but did impair eosinophil numbers in vivo. GAT eosinophils expressed IL-33Rα and IL-33 expanded eosinophil numbers in CD90(+) cell-depleted mice. IL-33 was further observed to induce the expression of retnla and epx mRNA in eosinophils. These findings demonstrate that IL-33 directly activates eosinophils in GAT, and together with our other findings described above, our findings show that IL-33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC-mediated pathway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Eosinophilic leukocytoclastic vasculitis - a spectrum ranging from Wells' syndrome to Churg-Strauss syndrome?

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Ratzinger, Gudrun; Zankl, Julia; Eisendle, Klaus; Zelger, Bernhard

2014-01-01

Wells' syndrome is defined as an inflammatory disorder with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Eosinophilic leukocytoclastic vasculitis shows eosinophilic infiltrates in combination with vasculitic changes. And Churg Strauss Syndrome comprises all three characteristics - eosinophilic infiltrates, vasculitis and flame figures. To determine whether these three diseases are distinct entities or different manifestations of a similar clinicopathologic process. Histopathological samples and clinical courses of 17 patients with eosinophilic infiltrates, flame figures and clinical features of Wells' syndrome were re-evaluated. Histopathologically, we focused on the presence or absence of vasculitic features. Clinically, we included only patients who were diagnosed with Wells' syndrome at least once in the course of their disease. 4 patients were finally diagnosed with Wells' syndrome, 5 with eosinophilic leukocytoclastic vasculitis and 6 with Churg Strauss syndrome. Further, we had one case of an overlap between Wells' syndrome and eosinophilic vasculitis and one case of Wegener granulomatosis. Vasculitic features were found in the samples of all patients. Histologically, we find vasculitic features in typical presentations of Wells' syndrome. Clinically, we find typical features of Wells' syndrome in patients finally diagnosed with eosinophilic leukocytoclastic vasculitis or Churg Strauss syndrome. Furthermore, we have observed and formerly reported 3 patients with progression from Wells' syndrome to Churg Strauss syndrome. Thus, we assume that eosinophilic leukocytoclastic vasculitis might form a bridge between Wells' syndrome and Churg Strauss syndrome.

5-Lipoxygenase-Dependent Recruitment of Neutrophils and Macrophages by Eotaxin-Stimulated Murine Eosinophils

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Ricardo Alves Luz

2014-01-01

Full Text Available The roles of eosinophils in antimicrobial defense remain incompletely understood. In ovalbumin-sensitized mice, eosinophils are selectively recruited to the peritoneal cavity by antigen, eotaxin, or leukotriene(LTB4, a 5-lipoxygenase (5-LO metabolite. 5-LO blockade prevents responses to both antigen and eotaxin. We examined responses to eotaxin in the absence of sensitization and their dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX; eosinophil-deficient GATA-1 were injected i.p. with eotaxin, eosinophils, or both, and leukocyte accumulation was quantified up to 24 h. Significant recruitment of eosinophils by eotaxin in BALB/c, up to 24 h, was accompanied by much larger numbers of recruited neutrophils and monocytes/macrophages. These effects were abolished by eotaxin neutralization and 5-LO-activating protein inhibitor MK886. In ALOX (but not PAS mice, eotaxin recruitment was abolished for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited neither neutrophils nor macrophages. Transfer of eosinophils cultured from bone-marrow of BALB/c donors, or from ALOX donors, into GATA-1 mutant recipients, i.p., restored eotaxin recruitment of neutrophils and showed that the critical step dependent on 5-LO is the initial recruitment of eosinophils by eotaxin, not the secondary neutrophil accumulation. Eosinophil-dependent recruitment of neutrophils in naive BALB/c mice was associated with increased binding of bacteria.

Severe Rhabdomyolysis without Systemic Involvement: A Rare Case of Idiopathic Eosinophilic Polymyositis

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Ayesha Farooq

2015-01-01

Full Text Available Introduction. Eosinophilic polymyositis (EPM is a rare cause of rhabdomyolysis characterized by eosinophilic infiltrates in the muscle. We describe the case of a young patient with eosinophilic polymyositis causing isolated severe rhabdomyolysis without systemic involvement. Case Presentation. A 22-year-old Haitian female with no past medical history presented with progressive generalized muscle aches without precipitating factors. Examination of the extremities revealed diffuse muscle tenderness. Laboratory findings demonstrated peripheral eosinophilia and high creatinine phosphokinase (CPK and transaminase levels. Workup for the common causes of rhabdomyolysis were negative. Her CPK continued to rise to greater than 100,000 units/L so a muscle biopsy was performed which showed widespread eosinophilic infiltrate consistent with eosinophilic polymyositis. She was started on high dose systemic corticosteroids with improvement of her symptoms, eosinophilia, and CPK level. Discussion. This case illustrates a systematic workup of rhabdomyolysis in the presence of peripheral eosinophilia. Many differential diagnoses must be considered before establishing a diagnosis of idiopathic eosinophilic polymyositis. To our knowledge, our case of eosinophilic polymyositis is unique as it presented with severe rhabdomyolysis without another organ involvement. Clinicians should maintain a high index of suspicion for this physically debilitating disease to aid in prompt diagnosis.

Canine Oral Eosinophilic Granuloma Treated with Electrochemotherapy

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Matías Nicolás Tellado

2014-01-01

Full Text Available A case of a canine oral eosinophilic granuloma in a 14-year-old female crossbred is described. The dog was presented with a history of ptyalism, halitosis, local pain, decreased appetite, and blood staining noted on food and water bowls. Clinical, hematologic, and biochemical examinations, abdominal ultrasonography, and 3-view chest radiographs were performed, and no metastases were found. Histopathologic examination of two 6 mm punch biopsies from the oral lesion revealed the presence of eosinophilic granulomatous lesions in the submucosa. After treatment with corticosteroids and wide spectrum antibiotics no significant changes in clinical signs and lesion size were observed. Electrochemotherapy (ECT, a novel tumor treatment routinely used for cutaneous and subcutaneous tumors in human patients in the European Union since 2006, was used to treat the eosinophilic granuloma. The procedure was performed under general anesthesia, followed by intravenous administration of bleomycin. Six weeks after treatment a complete response with disappearance of the mass and improvement of clinical signs were observed.

Eosinophil count, allergies, and rejection in pediatric heart transplant recipients.

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Arbon, Kate S; Albers, Erin; Kemna, Mariska; Law, Sabrina; Law, Yuk

2015-08-01

Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Development of Eosinophilic Fasciitis during Infliximab Therapy for Psoriatic Arthritis

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Richard Hariman

2016-01-01

Full Text Available 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.

Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils.

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Tamaki, Mami; Konno, Yasunori; Kobayashi, Yoshiki; Takeda, Masahide; Itoga, Masamichi; Moritoki, Yuki; Oyamada, Hajime; Kayaba, Hiroyuki; Chihara, Junichi; Ueki, Shigeharu

2014-07-01

Sexual dimorphism in asthma links the estrogen and allergic immune responses. The function of estrogen was classically believed to be mediated through its nuclear receptors, i.e., estrogen receptors (ERs). However, recent studies established the important roles of G-protein-coupled estrogen receptor (GPER/GPR30) as a novel membrane receptor for estrogen. To date, the role of GPER in allergic inflammation is poorly understood. The purpose of this study was to examine whether GPER might affect the functions of eosinophils, which play an important role in the pathogenesis of asthma. Here, we demonstrated that GPER was expressed in purified human peripheral blood eosinophils both at the mRNA and protein levels. Although GPER agonist G-1 did not induce eosinophil chemotaxis or chemokinesis, preincubation with G-1 enhanced eotaxin (CCL11)-directed eosinophil chemotaxis. G-1 inhibited eosinophil spontaneous apoptosis and caspase-3 activities. The anti-apoptotic effect was not affected by the cAMP-phospodiesterase inhibitor rolipram or phosphoinositide 3-kinase inhibitors. In contrast to resting eosinophils, G-1 induced apoptosis and increased caspase-3 activities when eosinophils were co-stimulated with IL-5. No effect of G-1 was observed on eosinophil degranulation in terms of release of eosinophil-derived neurotoxin (EDN). The current study indicates the functional capacities of GPER on human eosinophils and also provides the previously unrecognized mechanisms of interaction between estrogen and allergic inflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

MR findings of eosinophilic granuloma

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Choi, Jong O; Yee, Mi Kyeung; Cho, Kil Ho [Yeungnam Univ. College of Medicine, Kyongsan (Korea, Republic of); Lee, Sung Moon [Keimyung Univ. College of Medicine, Taegu (Korea, Republic of); Lee, Young Hwan [Hyosung Catholic Univ. College of Medicine, Taegu (Korea, Republic of); Suh, Kyung Jin [Suhjoo MR Clinic, Taegu (Korea, Republic of)

1999-06-01

To describe the MR findings for the three phases of eosinophilic granuloma, as defined by Mirra's conventional radiographic criteria. Eighteen lesions in 14 patients with proven eosinophilic granuloma were retrospectively analyzed. Among this total, three vertebral lesions were excluded, and the remaining is were classified as early, middle, or late phase on the basis of Mirra's radiographic criteria. For each phase, we compared MR findings with regard to signal intensity, homogeneity, contrast enhancement, perilesional marrow edema, and soft tissue change. For the three vertebral lesions excluded because the application of radiographic criteria was difficult, MR findings for paravertebral soft tissue reaction and degree of cord compression were compared. Of the fifteen cases classified, eight were early phase, five were mid phase, and two were late phase. During each phase, all lesions except one, as seen on T1-weighted images(T1WI), showed iso-signal intensity. On T2WI, all lesions showed high signal intensity. Contrast study demonstrated marked contrast enhancement. Thus, no remarkable differences were found in the signal intensity degree of contrast enhancement of each phase. With regard to heterogeneity, this was demonstrated in most early phase lesions, reflecting necrosis and hemorrhage of those lesions. Soft tissue swelling was more severe during the early phase than the mid or late phase, but marrow edema was similar in each of the three phase. One of three patients with vertebraplana showed para-vertebral soft tissue swelling and cord compression, but this was not seen in the two other cases. For evalvating the extent of eosinophilic granuloma and its relationship with surrounding structures, MRI was superior to conventional radiography. During the early phase of the disease, lesions showed greater inhomogeneity and more aggressive soft tissue reaction than during the mid and late phase.The use of MRI for the evalvation of eosinophilic granuloma

Eosinophilic Esophagitis: Symptoms and Causes

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... to GERD medication Failure to thrive (poor growth, malnutrition and weight loss) When to see a doctor ... Originally, eosinophilic esophagitis was thought to be a childhood disease, but now it is known to be ...

Eosinophilic Esophagitis: Diagnosis and Treatment

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... as fatty or fried foods, tomato sauce, alcohol, chocolate, mint, garlic, onion, and caffeine, may make heartburn ... the waist up. Alternative medicine No alternative medicine therapies have been proved to treat eosinophilic esophagitis. Still, ...

Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus.

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Samarasinghe, Amali E; Melo, Rossana C N; Duan, Susu; LeMessurier, Kim S; Liedmann, Swantje; Surman, Sherri L; Lee, James J; Hurwitz, Julia L; Thomas, Paul G; McCullers, Jonathan A

2017-04-15

Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus-infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8 + T cell numbers in the airways. In vitro assays with primary or bone marrow-derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide-exposed eosinophils induced CD8 + T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity. Copyright © 2017 by The American Association of Immunologists, Inc.

Eosinophils as a novel cell source of prostaglandin D2: autocrine role in allergic inflammation

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Luna-Gomes, Tatiana; Magalhães, Kelly G; Mesquita-Santos, Fabio P.; Bakker-Abreu, Ilka; Samico, Rafaela F.; Molinaro, Raphael; Calheiros, Andrea S.; Diaz, Bruno L.; Bozza, Patrícia T.

2011-01-01

Prostaglandin (PG)D2 is a key mediator of allergic inflammatory diseases that is mainly synthesized by mast cells, which constitutively express high levels of the terminal enzyme involved in PGD2 synthesis, the hematopoietic PGD synthase (H-PGDS). Here, we investigated whether eosinophils are also able to synthesize, and therefore, supply biologically active PGD2. PGD2 synthesis was evaluated within human blood eosinophils, in vitro-differentiated mouse eosinophils, and eosinophils infiltrating inflammatory site of mouse allergic reaction. Biological function of eosinophil-derived PGD2 was studied by employing inhibitors of synthesis and activity. Constitutive expression of H-PGDS was found within non-stimulated human circulating eosinophils. Acute stimulation of human eosinophils with A23187 (0.1 – 5 μM) evoked PGD2 synthesis, which was located at the nuclear envelope and was inhibited by pre-treatment with HQL-79 (10 μM), a specific H-PGDS inhibitor. Pre-stimulation of human eosinophils with arachidonic acid (AA; 10 μM) or human eotaxin (6 nM) also enhanced HQL-79-sensitive PGD2 synthesis, which, by acting on membrane-expressed specific receptors (DP1 and DP2), displayed an autocrine/paracrine ability to trigger leukotriene (LT)C4 synthesis and lipid body biogenesis, hallmark events of eosinophil activation. In vitro-differentiated mouse eosinophils also synthesized paracrine/autocrine active PGD2 in response to AA stimulation. In vivo, at late time point of the allergic reaction, infiltrating eosinophils found at the inflammatory site appeared as an auxiliary PGD2-synthesizing cell population. Our findings reveal that eosinophils are indeed able to synthesize and secrete PGD2, hence representing during allergic inflammation an extra cell source of PGD2, which functions as an autocrine signal for eosinophil activation. PMID:22102725

Assessment of Schistosoma mansoni induced intestinal inflammation by means of eosinophil cationic protein, eosinophil protein X and myeloperoxidase before and after treatment with praziquantel

DEFF Research Database (Denmark)

Reimert, Claus Michael; Tukahebwa, Edridah M.; Kabatereine, Narcis B.

2008-01-01

Faecal concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX) and myeloperoxidase (MPO) were measured in extracts of stool samples obtained from a cohort of people (n=182) living in Bugoigo, a fishing community on the Eastern shore of Lake Albert, Buliisa District, in North...

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

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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

Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders.

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Barnig, Cindy; Alsaleh, Ghada; Jung, Nicolas; Dembélé, Doulaye; Paul, Nicodème; Poirot, Anh; Uring-Lambert, Béatrice; Georgel, Philippe; de Blay, Fréderic; Bahram, Seiamak

2015-01-01

Eosinophils are leukocytes that are released into the peripheral blood in a phenotypically mature state and are capable of being recruited into tissues in response to appropriate stimuli. Eosinophils, traditionally considered cytotoxic effector cells, are leukocytes recruited into the airways of asthma patients where they are believed to contribute to the development of many features of the disease. This perception, however, has been challenged by recent findings suggesting that eosinophils have also immunomodulatory functions and may be involved in tissue homeostasis and wound healing. Here we describe a transcriptome-based approach-in a limited number of patients and controls-to investigate the activation state of circulating human eosinophils isolated by flow cytometry. We provide an overview of the global expression pattern in eosinophils in various relevant conditions, e.g., eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Compared to healthy subjects, circulating eosinophils isolated from asthma patients differed in their gene expression profile which is marked by downregulation of transcripts involved in antigen presentation, pathogen recognition and mucosal innate immunity, whereas up-regulated genes were involved in response to non-specific stimulation, wounding and maintenance of homeostasis. Eosinophils from other hypereosinophilic disorders displayed a very similar transcriptional profile. Taken together, these observations seem to indicate that eosinophils exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis and suggest new roles for these cells in asthma immunobiology.

Canine eosinophilic folliculitis and furunculosis in three cases.

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Curtis, C F; Bond, R; Blunden, A S; Thomson, D G; McNeil, P E; Whitbread, T W

1995-03-01

The historical, clinical and histopathological features of three dogs with eosinophilic folliculitis and furunculosis are described. The disease was characterised by the rapid development of pruritic, papular, pustular and ulcerative lesions on the dorsum of the muzzle. Skin lesions were confined to the face in two cases. The third dog had more generalised pustular lesions. Skin biopsy specimens showed marked eosinophil infiltration particularly centred on pilosebaceous units. Dermal collagen necrosis was evident in two cases. Similar facial lesions have previously been described as 'nasal pyoderma'. The three dogs failed to respond to initial antibacterial therapy but showed a rapid clinical response when prednisolone was given orally at doses ranging from 1 to 2.2 mg/kg, in addition to the antibacterial therapy, suggesting that glucocorticoids are indicated for the treatment of eosinophilic folliculitis and furunculosis. The aetiology of the disease was not determined.

The imaging diagnosis of costal solitary eosinophilic granuloma

International Nuclear Information System (INIS)

Cui Fa; Feng Shiting

2007-01-01

Objective: To study the imaging features of costal eosinophilic granuloma so as to improve diagnosis accuracy of the disease. Methods: The clinical and imaging materials of 6 patients with costal solitary eosinophilic granuloma which were proved by surgery or histopathology were analyzed retrospectively. X-ray plain films were performed in all the cases, CT in 3 cases, 2 cases were received CT plain scan and I case received both CT plain scan and enhanced CT scan. Results: 4 cases of them located in the anterior ribs. All the lesions were round-like and 5 were single cavity and 1 was multiple cavities. 3 of them were expansile destruction and 3 were cystic destruction. Soft tissue mass around the lesion was identified. Conclusion: X-ray plain films integrating CT play an important role in diagnosis and differential diagnosis of the costal eosinophilic granuloma. (authors)

Diffuse eosinophilic gastroenteritis with antral obstruction: a case report

International Nuclear Information System (INIS)

Moon, Sung Hee; Kim, Young Bok; Lee, Koung Hee

2000-01-01

Eosinophilic gastroenteritis is a rare disease characterized by tissue eosinophilia that can involve different layers of the gut wall and cause various gastrointestinal symptoms. We describe the UGI and CT findings of a case of diffuse eosinophilic gastroenteritis with tumor-like antral obstruction due to thickening of the submucosa and muscle layer in a 21-year-old male. (author)

Diffuse eosinophilic gastroenteritis with antral obstruction: a case report

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Moon, Sung Hee; Kim, Young Bok; Lee, Koung Hee [National Police Hospital, Seoul (Korea, Republic of)

2000-02-01

Eosinophilic gastroenteritis is a rare disease characterized by tissue eosinophilia that can involve different layers of the gut wall and cause various gastrointestinal symptoms. We describe the UGI and CT findings of a case of diffuse eosinophilic gastroenteritis with tumor-like antral obstruction due to thickening of the submucosa and muscle layer in a 21-year-old male. (author)

A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst

DEFF Research Database (Denmark)

Royer, J F; Schratl, P; Lorenz, S

2007-01-01

developed small molecule antagonist of CRTH2, Cay10471, on eosinophil function with respect to recruitment, respiratory burst and degranulation. METHODS: Chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils were determined using microBoyden chambers. Eosinophil release...... from bone marrow was investigated in the in situ perfused guinea pig hind limb preparation. Respiratory burst and degranulation were measured by flow cytometry. RESULTS: Cay10471 bound with high affinity to recombinant human and guinea pig CRTH2, but not DP, receptors. The antagonist prevented the PGD......(2)-induced release of eosinophils from guinea pig bone marrow, and inhibited the chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils. Pretreatment with PGD(2) primed eosinophils for chemotaxis towards eotaxin, and this effect was prevented by Cay10471. In contrast...

Mechanisms of eosinophil adhesion to endothelial cells under flow conditions

NARCIS (Netherlands)

Ulfman, L.H.

2002-01-01

Eosinophils play an important role in allergic inflammatory diseases such as allergic asthma. Infiltrates of these cells are present in the interstitium and the lumen of the bronchi of asthmatic patients. Eosinophils must pass the endothelium to enter this site of inflammation. A widely accepted

Eosinophils in biopsy specimens of lichen sclerosus: a not uncommon finding.

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Lester, Elizabeth B; Swick, Brian L

2015-01-01

Evolving lesions of lichen sclerosus (LS) pose a diagnostic challenge owing to an absence of classic findings of epidermal atrophy, dermal sclerosis, a band-like lymphocytic infiltrate and the presence of eosinophils. Retrospective specimens of LS were reviewed. Demographic information, biopsy vs. excision and the following histopathological characteristics were noted: presence and number of eosinophils, epidermal hyperplasia, spongiosis, early/transitional LS, well-developed LS and coexisting squamous cell carcinoma (SCC). Linear regression analysis was performed. The data consisted of 66 biopsies (36 male [M], 30 female [F]), from 53 individuals (33M, 20F), including 57 genital and 9 extragenital biopsies. Seven biopsies showed SCC, 28 showed epidermal hyperplasia and 14 exhibited spongiosis. Thirty-five specimens were early/transitional LS and commonly exhibited epidermal hyperplasia (57%), epidermotropism of lymphocytes (97%) and basement membrane thickening (97%). Thirty-five biopsies (53%) contained eosinophils (23 early/transitional lesions). Male gender (p = 0.074) was associated with increased eosinophils. The presence of SCC (p = 0.014) was a significant predictors of eosinophil number. Epidermal hyperplasia, epidermotropism of lymphocytes and basement membrane thickening are helpful features in identifying early LS. Eosinophils are not an uncommon finding in LS and are most common in male genital lesions and in LS associated with SCC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bronchoalveolar lavage and technetium-99m glucoheptonate imaging in chronic eosinophilic pneumonia

International Nuclear Information System (INIS)

Lieske, T.R.; Sunderrajan, E.V.; Passamonte, P.M.

1984-01-01

A patient with chronic eosinophilic pneumonia was evaluated using bronchoalveolar lavage, technetium-99m glucoheptonate, and transbronchial lung biopsy. Bronchoalveolar lavage revealed 43 percent eosinophils and correlated well with results of transbronchial lung biopsy. Technetium-99m glucoheptonate lung imaging demonstrated intense parenchymal uptake. After eight weeks of corticosteroid therapy, the bronchoalveolar lavage eosinophil population and the technetium-99m glucoheptonate uptake had returned to normal. We suggest that bronchoalveolar lavage, with transbronchial lung biopsy, is a less invasive way than open lung biopsy to diagnose chronic eosinophilic pneumonia. The mechanism of uptake of technetium-99m glucoheptonate in this disorder remains to be defined

Work in progress: radionuclide imaging of indium-111-labeled eosinophils in mice

International Nuclear Information System (INIS)

Runge, V.M.; Rand, T.H.; Clanton, J.A.; Jones, J.P.; Colley, D.G.; Partain, C.L.; James, A.E. Jr.

1983-01-01

Eosinophils isolated from peritoneal exudates were labeled with indium-111-oxine and injected intravenously into sensitized mice. They became localized at sites of inflammation produced by intradermal injections of schistosomal antigen or Toxocara canis larvae, whereas labeled neutrophils did not. Intense uptake of eosinophils by normal spleen, liver, and bone marrow was noted, with tracer distribution effectively complete by 5 hours after injection. Indium-111-eosinophil studies appear to be quite sensitive to parasitic inflammatory reactions; in contrast, nonspecific inflammation such as that induced by turpentine causes localization of eosinophils, but to a lesser extent. This technique may be useful in the study of parasitic and allergic disease

Eosinophilic meningitis: a case series and review of literature of Angiostrongylus cantonensis and Gnathostoma spinigerum.

Science.gov (United States)

Shah, I; Barot, S; Madvariya, M

2015-01-01

Eosinophilic meningitis is defined as the presence of >10 eosinophils/μL in cerebrospinal fluid (CSF) or at least 10% eosinophils in the total CSF leukocyte count. Eosinophilic meningitis has been reported in two case series and two case reports in India till date and has not been reported in children below 15 years of age. We present two children with eosinophilic meningitis with peripheral eosinophilia and the proposed etiologic agents based on the clinical setting and their response to antihelminthic agents.

Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice.

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Jacobsen, E A; Doyle, A D; Colbert, D C; Zellner, K R; Protheroe, C A; LeSuer, W E; Lee, N A; Lee, J J

2015-09-01

Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Wild-type or cytokine-deficient (IL-13(-/-) or IL-4(-/-) ) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4(+) T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4(+) T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role. The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eosinophilic fasciitis after parasite infection

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Marta Oliveira

2016-03-01

Full Text Available 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.

Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro

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Alves Alessandra C

1997-01-01

Full Text Available In the present study, we have performed a comparative analysis of the effect of selective inhibitors of phosphodiesterase (PDE type III, IV and V on eosinophil chemotaxis triggered by platelet activating factor (PAF and leukotriene B4 (LTB4 in vitro. The effect of the analogues N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt2 cyclic AMP and N2-2'-O- dibutyrylguanosine 3':5' cyclic monophosphate (Bt2 cyclic GMP has also been determined. The eosinophils were obtained from the peritoneal cavity of naive Wistar rats and purified in discontinuous Percoll gradients to 85-95% purity. We observed that pre-incubation of eosinophils with the PDE type IV inhibitor rolipram suppressed the chemotactic response triggered by PAF and LTB4, in association with an increase in the intracellular levels of cyclic AMP. In contrast, neither zaprinast (type V inhibitor nor type III inhibitors milrinone and SK&F 94836 affected the eosinophil migration. Only at the highest concentration tested did the analogue Bt2 cyclic AMP suppress the eosinophil chemotaxis, under conditions where Bt2 cyclic GMP was ineffective. We have concluded that inhibition of PDE IV, but not PDE III or V, was able to block the eosinophil chemotaxis in vitro, suggesting that the suppressive activity of selective PDE IV inhibitors on tissue eosinophil accumulation may, at least, be partially dependent on their ability to directly inhibit the eosinophil migration.

TLR-Stimulated Eosinophils Mediate Recruitment and Activation of NK Cells In Vivo.

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O'Flaherty, S M; Sutummaporn, K; Häggtoft, W L; Worrall, A P; Rizzo, M; Braniste, V; Höglund, P; Kadri, N; Chambers, B J

2017-06-01

Eosinophils like many myeloid innate immune cells can provide cytokines and chemokines for the activation of other immune cells upon TLR stimulation. When TLR-stimulated eosinophils were inoculated i.p. into wild-type mice, and NK cells were rapidly recruited and exhibited antitumour cytotoxicity. However, when mice depleted of CD11c + cells were used, a marked decrease in the number of recruited NK cells was observed. We postulated that CpG or LPS from the injected eosinophils could be transferred to host cells, which in turn could recruit NK cells. However, by inoculating mice deficient in TLR4 or TLR9 with LPS or CpG-stimulated eosinophils respectively, NK cell recruitment was still observed alongside cytotoxicity and IFNγ production. CpG stimulation of eosinophils produced the pro-inflammatory cytokine IL-12 and the chemokine CXCL10, which are important for NK cell activation and recruitment in vivo. To demonstrate the importance of CXCL10 in NK cell recruitment, we found that CpG-stimulated eosinophils pretreated with the gut microbial metabolite butyrate had reduced expression and production of CXCL10 and IL-12 and concomitantly were poor at recruitment of NK cells and inducing IFNγ in NK cells. Therefore, eosinophils like other innate immune cells of myeloid origin can conceivably stimulate NK cell activity. In addition, products of the gut microbiota can be potential inhibitors of NK cell. © 2017 The Foundation for the Scandinavian Journal of Immunology.

Synergic production of neutrophil chemotactic activity by colonic epithelial cells and eosinophils.

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Dent, Gordon; Loweth, Sam C; Hasan, Anwar Matar; Leslie, Fiona M

2014-10-01

The presence of eosinophils in the lumen and mucosa of the intestine is characteristic of both ulcerative colitis (UC) and Crohn's disease (CD). There is evidence of eosinophil activation in the intestine during acute inflammatory episodes of these diseases; these episodes are also characterized by an influx of neutrophils, which have the potential to cause extensive tissue damage. We undertook a study to determine whether eosinophils in contact with colonic epithelial cells produce factors that may attract neutrophils in response to immunological stimulation. Neutrophil chemotactic activity (NCA) and concentrations of three neutrophil-attracting CXC chemokines - CXCL1 (Groα), CXCL5 (Ena78) and CXCL8 (IL8) - were measured in supernatants of T84 colonic epithelial cells and blood eosinophils or eosinophil-like myeloid leukaemia cells (AML14.3D10), alone or in combination. Cells were stimulated with serum-opsonized zymosan (OZ) particles. NCA (Peosinophil co-cultures were significantly higher than in the supernatants of either cell type alone. Release of CXCL1 (Peosinophils but not higher than from OZ-stimulated epithelial cells. Eosinophils and colonic epithelial cells exhibit synergy in production of neutrophil chemoattractants in response to immunological stimulation. This may represent a mechanism for exaggerated recruitment of neutrophils to the intestine in response to acute infection in conditions that are characterized by the presence of eosinophils in the bowel. Copyright © 2014 Elsevier GmbH. All rights reserved.

Functional and phenotypic evaluation of eosinophils from patients with the acute form of paracoccidioidomycosis.

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Braga, Fernanda Gambogi; Ruas, Luciana Pereira; Pereira, Ricardo Mendes; Lima, Xinaida Taligare; Antunes, Edson; Mamoni, Ronei Luciano; Blotta, Maria Heloisa Souza Lima

2017-05-01

Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment. However, the role of eosinophils in PCM has never been evaluated. This study aimed to assess the phenotypic and functional characteristics of eosinophils in PCM. In 15 patients with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES) and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were higher levels of chemokines and granule proteins in the peripheral blood of patients compared to controls. Isolation of eosinophils from blood revealed a higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls, and a lower population of CD80+ cells. We also evaluated the fungicidal capacity of eosinophils in vitro. Our results revealed that eosinophils from PCM patients and controls exhibit similar ability to kill P. brasiliensis yeast cells, although eosinophils of patients were less responsive to IL-5 stimulation than controls. In conclusion, we suggest that eosinophils might play a role in the host response to fungi and in the pathophysiology of PCM by inducing an intense and systemic inflammatory response in the initial phase of the infection.

Increased CD69 Expression on Peripheral Eosinophils from Patients with Food Protein-Induced Enterocolitis Syndrome.

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Wada, Taizo; Matsuda, Yusuke; Toma, Tomoko; Koizumi, Eiko; Okamoto, Hiroyuki; Yachie, Akihiro

2016-01-01

Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE-mediated food allergy. We recently described a significant increase in fecal eosinophil-derived neurotoxin (EDN) after ingestion of the causative food. However, little is known about the activation status of circulating eosinophils in patients with an acute FPIES reaction. Surface CD69 expression was assessed by flow cytometry on peripheral eosinophils from 5 patients with FPIES before and after ingestion of the causative food. Fecal EDN was measured by enzyme-linked immunosorbent assay. No eosinophil activation was observed before ingestion; however, a significant increase in CD69 expression on eosinophils after an acute FIPES reaction was demonstrated in all of the patients. There was no significant change in absolute eosinophil counts in the peripheral blood. The levels of fecal EDN increased on the day after ingestion of the causative food in all patients. These results suggest that circulating eosinophils as well as eosinophils in the intestinal mucosal tissue are activated in acute FPIES reactions and might be associated with systemic immune events in FPIES. © 2016 S. Karger AG, Basel.

MR findings of calvarial eosinophilic granuloma

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Choi, Gi Bok; Son, Seok Hyun; Eun, Choong Ki; Park, Sung Kun; Han, Sang Suk [Pusan Paik Hospital, Inje Univ., Pusan (Korea, Republic of); Choi, Sun Seob [Donga Univ. College of Medicine, Pusan (Korea, Republic of); Kim, Seong Min [Kosin Univ. College of Medicine, Pusan (Korea, Republic of); Kim, Chang Soo [Maryknoll Hospital, Pusan (Korea, Republic of)

2001-03-01

The purpose of this study was to evaluate the MR findings of calvarial eosinophilic granuloma. We reviewed the MR imaging studies of nine patients [M:F=3:6, aged 6-35 (mean, 20.5) years] with pathologically proven eosinophilic granuloma in the calvaria. The findings were evaluated for involvement of the diploic space, changes in adjacent bone marrow, distinction of the transitional zone, pattern of bone destruction, signal intensity and contrast enhancement of the tumor, and contrast enhancement of the adjacent dura. All lesions involved the diploic space, showed no change in adjacent bone marrow, and had a distinct transitional zone. In most (8/9) cases there was asymmetric bony destruction. On T1-weighted images, signal intensities of the tumors varied, while on T2-weighted images, hyperintensity was observed in seven cases, isointensity in one, and hypointensity in one. After the administration of contrast material, enhancement was homogeneous in four cases and inhomogeneous in five. Enhancement of the adjacent dura was demonstrated in all nine cases. The characteristic MR findings of calvarial eosinophilic granuloma are variable signal intensity on T1WI, high signal intensity on T2WI, and marked contrast enhancement; in addition, there is a distinct transitional zone, asymmetrical bony destruction, and associated dural enhancement.

A pilot study of omalizumab in eosinophilic esophagitis.

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Denise Loizou

Full Text Available Eosinophilic disorders of the gastrointestinal tract are an emerging subset of immune pathologies within the spectrum of allergic inflammation. Eosinophilic Esophagitis (EoE, once considered a rare disease, is increasing in incidence, with a rate of over 1 in 10,000 in the US, for unknown reasons. The clinical management of EoE is challenging, thus there is an urgent need for understanding the etiology and pathophysiology of this eosinophilic disease to develop better therapeutic approaches. In this open label, single arm, unblinded study, we evaluated the effects of an anti-IgE treatment, omalizumab, on local inflammation in the esophagus and clinical correlates in patients with EoE. Omalizumab was administered for 12 weeks to 15 subjects with long standing EoE. There were no serious side effects from the treatment. Esophageal tissue inflammation was assessed both before and after therapy. After 3 months on omalizumab, although tissue Immunoglobulin E (IgE levels were significantly reduced in all but two of the subjects, we found that full remission of EoE, which is defined as histologic and clinical improvement only in 33% of the patients. The decrease in tryptase-positive cells and eosinophils correlated significantly with the clinical outcome as measured by improvement in endoscopy and symptom scores, respectively. Omalizumab-induced remission of EoE was limited to subjects with low peripheral blood absolute eosinophil counts. These findings demonstrate that in a subset of EoE patients, IgE plays a role in the pathophysiology of the disease and that anti-IgE therapy with omalizumab may result in disease remission. Since this study is open label there is the potential for bias, hence the need for a larger double blind placebo controlled study. The data presented in this pilot study provides a foundation for proper patient selection to maximize clinical efficacy.

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

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

2015-01-01

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

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

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Carmo, Lívia A.S.; Dias, Felipe F.; Malta, Kássia K.; Amaral, Kátia B. [Laboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora, UFJF, Juiz de Fora, MG (Brazil); Shamri, Revital; Weller, Peter F. [Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States); Melo, Rossana C.N., E-mail: rossana.melo@ufjf.edu.br [Laboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora, UFJF, Juiz de Fora, MG (Brazil); Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States)

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

Beta 2-adrenergic receptors on eosinophils. Binding and functional studies

International Nuclear Information System (INIS)

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

1990-01-01

We have studied the binding characteristics and functional effects of beta-adrenoceptors on human and guinea pig eosinophils. We determined the binding of the beta-antagonist radioligand [125I]pindolol (IPIN) to intact eosinophils obtained from the peritoneal cavity of guinea pigs and from blood of patients with eosinophilia. Specific binding was saturable, and Scatchard analysis showed a single binding site with a dissociation constant (Kd) of 24.6 pM and maximal number of binding sites (Bmax) of 7,166 per cell. ICI 118,551, a beta 2-selective antagonist, inhibited IPIN binding with a Ki value of 0.28 nM and was approximately 5,000-fold more effective than the beta 1-selective antagonist, atenolol. Isoproterenol increased cAMP levels about 5.5-fold above basal levels (EC50 = 25 microM); albuterol, a beta 2-agonist, behaved as a partial agonist with a maximal stimulation of 80%. Binding to human eosinophils gave similar results with a Kd of 25.3 pM and a Bmax corresponding to 4,333 sites per cell. Incubation of both human and guinea pig eosinophils with opsonized zymosan (2 mg/ml) or with phorbol myristate acetate (PMA) (10(-8) and 10(-6) M) resulted in superoxide anion generation and the release of eosinophil peroxidase; albuterol (10(-7) to 10(-5) M) had no inhibitory effect on the release of these products. Thus, eosinophils from patients with eosinophilia and from the peritoneal cavity of guinea pigs possess beta-receptors of the beta 2-subtype that are coupled to adenylate cyclase; however, these receptors do not modulate oxidative metabolism or degranulation. The possible therapeutic consequences of these observations to asthma are discussed

Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

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Liu, L Y; Wang, H; Xenakis, J J; Spencer, L A

2015-07-01

Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hydrodynamic property of the cytoplasm is sufficient to mediate cytoplasmic streaming in the Caenorhabiditis elegans embryo

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Niwayama, Ritsuya; Shinohara, Kyosuke; Kimura, Akatsuki

2011-01-01

Cytoplasmic streaming is a type of intracellular transport widely seen in nature. Cytoplasmic streaming in Caenorhabditis elegans at the one-cell stage is bidirectional; the flow near the cortex (“cortical flow”) is oriented toward the anterior, whereas the flow in the central region (“cytoplasmic flow”) is oriented toward the posterior. Both cortical flow and cytoplasmic flow depend on non-muscle-myosin II (NMY-2), which primarily localizes in the cortex. The manner in which NMY-2 proteins drive cytoplasmic flow in the opposite direction from remote locations has not been fully understood. In this study, we demonstrated that the hydrodynamic properties of the cytoplasm are sufficient to mediate the forces generated by the cortical myosin to drive bidirectional streaming throughout the cytoplasm. We quantified the flow velocities of cytoplasmic streaming using particle image velocimetry (PIV) and conducted a three-dimensional hydrodynamic simulation using the moving particle semiimplicit method. Our simulation quantitatively reconstructed the quantified flow velocity distribution resolved through PIV analysis. Furthermore, our PIV analyses detected microtubule-dependent flows during the pronuclear migration stage. These flows were reproduced via hydrodynamic interactions between moving pronuclei and the cytoplasm. The agreement of flow dynamics in vivo and in simulation indicates that the hydrodynamic properties of the cytoplasm are sufficient to mediate cytoplasmic streaming in C. elegans embryos. PMID:21730185

Protective Role of Eosinophils and TNFa after Ozone Inhalation.

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Fryer, Allison D; Jacoby, David B; Wicher, Sarah A

2017-03-01

Exposure to ozone induces deleterious responses in the airways that include shortness of breath, inflammation, and bronchoconstriction. People with asthma have increased airway sensitivity to ozone and other irritants. Dr. Allison Fryer and colleagues addressed how exposure to ozone affects the immune and physiological responses in guinea pigs. Guinea pigs are considered a useful animal model for studies of respiratory and physiological responses in humans; their response to airborne allergens is similar to that in humans and shares some features of allergic asthma. Fryer and colleagues had previously observed that within 24 hours of exposure, ozone not only induced bronchoconstriction but also stimulated the production of new cells in the bone marrow, where all white blood cells develop. As a result of ozone exposure, increased numbers of newly synthesized white blood cells, particularly eosinophils, moved into the blood and lungs. The central hypothesis of the current study was that newly synthesized eosinophils recruited to the lungs 3 days after ozone exposure were beneficial to the animals because they reduced ozoneinduced bronchoconstriction. The investigators also hypothesized that the beneficial effect seen in normal (nonsensitized) animals was lost in animals that had been injected with an allergen, ovalbumin (sensitized). They also planned to explore the effects of inhibitors of certain cytokines (cellsignaling molecules). Immune responses in sensitized animals are dominated by a Th2 pattern, which is characterized by the synthesis of cytokines (interleukin [IL]-4, IL-5, and IL-13) and the Th2 subset of CD4+ T lymphocytes and the cells they activate (predominantly eosinophils, and B lymphocytes that switch to making immunoglobulin E [IgE]). Thus, sensitized animals were used as a model of allergic humans, whose immune responses tend to be dominated by IgE. Fryer and colleagues exposed normal and sensitized (allergic) guinea pigs to 2 ppm ozone or filtered

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) presenting as diffuse myositis.

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Parent, Marc-Etienne; Larue, Sandrine; Ellezam, Benjamin

2014-11-21

Eosinophilic granulomatosis with polyangiitis is a complex multisystemic syndrome with heterogeneous presentation. Most often, there is a clinical history of asthma or other atopic conditions, and current presentation generally includes signs of cutaneous or pulmonary involvement. Very few reports described myalgia or weakness as the chief complaint. Of these, only a few included muscle biopsy evaluation and none showed convincing evidence of primary myositis. We believe this report is the first to demonstrate true myositis in the setting of early eosinophilic granulomatosis with polyangiitis. This report describes a 74 year old Caucasian man, with no known allergies, presenting severe myalgia, muscle weakness, jaw claudication, and fever. Blood work showed marked eosinophilia and high creatine kinase levels. Biceps brachialis muscle biopsy revealed eosinophilic necrotizing vasculitis and true myositis with myophagocytosis of non-necrotic fibers and strong sarcolemmal MHC-1 overexpression by immunohistochemistry. This patient was successfully treated with prednisone and azathioprine. Our finding of true myositis in a case of eosinophilic granulomatosis with polyangiitis suggests that primary auto-immunity against muscle fibers, distinct from the secondary effects of vasculitis, can occur in this entity and may represent an overlap syndrome. Early recognition of eosinophilic granulomatosis with polyangiitis in patients presenting with myositis may provide an opportunity to treat the vasculitis before onset of severe multisystemic disease. We recommend the use of muscle biopsy with immunohistochemistry for MHC-1 to confirm the diagnosis of myositis in the setting of eosinophilic granulomatosis with polyangiitis.

Differential Activation of Airway Eosinophils Induces IL-13 Mediated Allergic Th2 Pulmonary Responses in Mice

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Jacobsen, EA; Doyle, AD; Colbert, DC; Zellner, KR; Protheroe, CA; LeSuer, WE; Lee, NA.; Lee, JJ

2015-01-01

Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild type or cytokine deficient (IL-13−/− or IL-4−/−) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophildeficient mice, which induced no immune/inflammatory changes either in the lung or lung draining lymph nodes (LDLNs), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLNs. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4 and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13 whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. PMID:26009788

Immunophenotyping of eosinophils recovered from blood and BAL of allergic asthmatics

NARCIS (Netherlands)

Mengelers, H. J.; Maikoe, T.; Brinkman, L.; Hooibrink, B.; Lammers, J. W.; Koenderman, L.

1994-01-01

Studies of bronchoalveolar lavage (BAL) fluid from patients with allergic asthma have demonstrated active migration of eosinophils into the bronchial lumen after allergen challenge. The mechanisms mediating this eosinophil infiltration and cell activation are largely unexplained. The expression of

Eosinophilic esophageal myositis diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: a case report.

Science.gov (United States)

Igarashi, Ryo; Irisawa, Atsushi; Shibukawa, Goro; Yamabe, Akane; Fujisawa, Mariko; Sato, Ai; Maki, Takumi; Arakawa, Noriyuki; Yoshida, Yoshitsugu; Yamamoto, Shogo; Ikeda, Tsunehiko

2016-10-01

Eosinophilic esophagitis (EoE) is diagnosed by microscopic findings of eosinophilic infiltration into the squamous epithelium. In contrast, another disease concept termed "eosinophilic esophageal myositis (EoEM)" has been proposed, whereby there is eosinophilic infiltration into the muscularis propria instead. A 60-year-old man was referred to our hospital for chest pain, dysphagia, and several episodes of esophageal food impaction. Although EoE was suspected based on clinical features, biopsy specimens showed no mucosal eosinophilic infiltration. Endoscopic ultrasound (EUS) showed thickening of the muscularis propria layer and subsequent EUS-guided fine-needle aspiration biopsy (EUS-FNA) revealed eosinophilic infiltration into the muscularis propria. Although the patient's symptoms gradually improved after steroid administration, complete remission was not achieved after 1 year of treatment. This case may reflect a disorder distinct from typical EoE based on eosinophilic infiltration of the muscularis propria but not the squamous epithelium, and we, therefore, diagnosed it as EoEM using the EUS-FNA findings as reference.

Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils.

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Stubbs, Victoria E L; Schratl, Petra; Hartnell, Adele; Williams, Timothy J; Peskar, Bernhard A; Heinemann, Akos; Sabroe, Ian

2002-07-19

We investigated the actions of a panel of nonsteroidal anti-inflammatory drugs on eosinophils, basophils, neutrophils, and monocytes. Indomethacin alone was a potent and selective inducer of eosinophil and basophil shape change. In eosinophils, indomethacin induced chemotaxis, CD11b up-regulation, respiratory burst, and L-selectin shedding but did not cause up-regulation of CD63 expression. Pretreatment of eosinophils with indomethacin also enhanced subsequent eosinophil shape change induced by eotaxin, although treatment with higher concentrations of indomethacin resulted in a decrease in the expression of the major eosinophil chemokine receptor, CCR3. Indomethacin activities and cell selectivity closely resembled those of prostaglandin D(2) (PGD(2)). Eosinophil shape change in response to eotaxin was inhibited by pertussis toxin, but indomethacin- and PGD(2)-induced shape change responses were not. Treatment of eosinophils with specific inhibitors of phospholipase C (U-73122), phosphatidylinositol 3-kinase (LY-294002), and p38 mitogen-activated protein kinase (SB-202190) revealed roles for these pathways in indomethacin signaling. Indomethacin and its analogues may therefore provide a structural basis from which selective PGD(2) receptor small molecule antagonists may be designed and which may have utility in the treatment of allergic inflammatory disease.

Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal fibroblasts.

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Shin, Seung-Heon; Ye, Mi-Kyung; Choi, Sung-Yong; Kim, Yee-Hyuk

2016-06-01

Eosinophils and fibroblasts are known to play major roles in the pathogenesis of nasal polyps. Fungi are commonly found in nasal secretion and are associated with airway inflammation. To investigate whether activated eosinophils by airborne fungi can influence the production of extracellular matrix (ECM) from nasal fibroblasts. Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria or Aspergillus, respectively, for 24 hours and ECM messenger RNA (mRNA) and protein expressions were measured. Eosinophils isolated from healthy volunteers were stimulated with Alternaria or Aspergillus for 4 hours then superoxide, eosinophil peroxidase, and transforming growth factor β1 were measured. Then activated eosinophils were cocultured with nasal fibroblasts for 24 hours, and ECM mRNA expressions were measured. Alternaria strongly enhanced ECM mRNA expression and protein production from nasal fibroblasts. Alternaria also induced the production of superoxide, eosinophil peroxidase, and transforming growth factor β1 from eosinophils, and activated eosinophils enhanced ECM mRNA expression when they were cocultured without the Transwell insert system. Eosinophils activated with Alternaria enhanced ECM mRNA expression from nasal polyp fibroblasts. Alternaria plays an important role in tissue fibrosis in the pathogenesis of nasal polyps by directly or indirectly influencing the production of ECM from nasal fibroblasts. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A key requirement for CD300f in innate immune responses of eosinophils in colitis.

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Moshkovits, I; Reichman, H; Karo-Atar, D; Rozenberg, P; Zigmond, E; Haberman, Y; Ben Baruch-Morgenstern, N; Lampinen, M; Carlson, M; Itan, M; Denson, L A; Varol, C; Munitz, A

2017-01-01

Eosinophils are traditionally studied in the context of type 2 immune responses. However, recent studies highlight key innate immune functions for eosinophils especially in colonic inflammation. Surprisingly, molecular pathways regulating innate immune activities of eosinophil are largely unknown. We have recently shown that the CD300f is highly expressed by colonic eosinophils. Nonetheless, the role of CD300f in governing innate immune eosinophil activities is ill-defined. RNA sequencing of 162 pediatric Crohn's disease patients revealed upregulation of multiple Cd300 family members, which correlated with the presence of severe ulcerations and inflammation. Increased expression of CD300 family receptors was also observed in active ulcerative colitis (UC) and in mice following induction of experimental colitis. Specifically, the expression of CD300f was dynamically regulated in monocytes and eosinophils. Dextran sodium sulfate (DSS)-treated Cd300f -/- mice exhibit attenuated disease activity and histopathology in comparison with DSS-treated wild type (WT). Decreased disease activity in Cd300f -/- mice was accompanied with reduced inflammatory cell infiltration and nearly abolished production of pro-inflammatory cytokines. Monocyte depletion and chimeric bone marrow transfer experiments revealed a cell-specific requirement for CD300f in innate immune activation of eosinophils. Collectively, we uncover a new pathway regulating innate immune activities of eosinophils, a finding with significant implications in eosinophil-associated gastrointestinal diseases.

Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease

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Uderhardt, Stefan; Ackermann, Jochen A.; Fillep, Tobias; Hammond, Victoria J.; Willeit, Johann; Stark, Konstantin; Rossaint, Jan; Schubert, Irene; Mielenz, Dirk; Dietel, Barbara; Raaz-Schrauder, Dorette; Ay, Cihan; Thaler, Johannes; Heim, Christian; Collins, Peter W.; Schabbauer, Gernot; Mackman, Nigel; Voehringer, David; Nadler, Jerry L.; Lee, James J.; Massberg, Steffen; Rauh, Manfred; O’Donnell, Valerie B.

2017-01-01

Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease. PMID:28566277

Echocardiographic Changes in Eosinophilic Endocarditis Induced by Churg-Strauss Syndrome.

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Masaki, Nobuyuki; Issiki, Ami; Kirimura, Masato; Kamiyama, Tetsuo; Sasaki, Osamu; Ito, Hiroyuki; Maruyama, Yoshiaki; Nishioka, Toshihiko

Eosinophilic myocarditis may be accompanied by Churg-Strauss syndrome (CSS). We report a case of CSS that was accompanied by myocardial changes in the early stage. A 71-year-old woman complained of mild chest pain at rest, but routine echocardiography did not reveal any endocardial abnormalities. Four months later, the patient was hospitalized due to congestive heart failure with neuropathy of both upper extremities. A diagnosis of eosinophilic myocarditis was made based on the patient's laboratory results and the presence of mural thrombus. This case illustrates that, although early eosinophilic myocarditis is an important differential diagnosis in patients with chest pain, it may be difficult to identify in without an apparent mural thrombus.

Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients.

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Wright, Adam; Mahaut-Smith, Martyn; Symon, Fiona; Sylvius, Nicolas; Ran, Shaun; Bafadhel, Mona; Muessel, Michelle; Bradding, Peter; Wardlaw, Andrew; Vial, Catherine

2016-06-15

Eosinophils play an important role in the pathogenesis of asthma and can be activated by extracellular nucleotides released following cell damage or inflammation. For example, increased ATP concentrations were reported in bronchoalveolar lavage fluids of asthmatic patients. Although eosinophils are known to express several subtypes of P2 receptors for extracellular nucleotides, their function and contribution to asthma remain unclear. In this article, we show that transcripts for P2X1, P2X4, and P2X5 receptors were expressed in healthy and asthmatic eosinophils. The P2X receptor agonist α,β-methylene ATP (α,β-meATP; 10 μM) evoked rapidly activating and desensitizing inward currents (peak 18 ± 3 pA/pF at -60 mV) in healthy eosinophils, typical of P2X1 homomeric receptors, which were abolished by the selective P2X1 antagonist NF449 (1 μM) (3 ± 2 pA/pF). α,β-meATP-evoked currents were smaller in eosinophils from asthmatic patients (8 ± 2 versus 27 ± 5 pA/pF for healthy) but were enhanced following treatment with a high concentration of the nucleotidase apyrase (17 ± 5 pA/pF for 10 IU/ml and 11 ± 3 pA/pF for 0.32 IU/ml), indicating that the channels are partially desensitized by extracellular nucleotides. α,β-meATP (10 μM) increased the expression of CD11b activated form in eosinophils from healthy, but not asthmatic, donors (143 ± 21% and 108 ± 11% of control response, respectively). Furthermore, α,β-meATP increased healthy (18 ± 2% compared with control 10 ± 1%) but not asthmatic (13 ± 1% versus 10 ± 0% for control) eosinophil adhesion. Healthy human eosinophils express functional P2X1 receptors whose activation leads to eosinophil αMβ2 integrin-dependent adhesion. P2X1 responses are constitutively reduced in asthmatic compared with healthy eosinophils, probably as the result of an increase in extracellular nucleotide concentration. Copyright © 2016 by The American Association of Immunologists, Inc.

Leukotriene Receptor Antagonists in the Treatment of Asthma: Implications for Eosinophilic Inflammation

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Redwan Moqbel

1999-01-01

Full Text Available Recent advances in the treatment and management of asthma have suggested that leukotriene (LT receptor antagonists may be very beneficial as a second generation therapy with steroid-sparing properties and negligible side effects. These agents have shown interesting effects on peripheral blood and sputum eosinophils. A major contributor to the damage in the airway of asthmatic patients is the eosinophil, which, upon activation, releases a battery of granule-associated cytotoxic, cationic proteins, including the major basic protein and eosinophil peroxidase, and membrane-derived de novo-synthesized bioactive lipid mediators, including LTC4, LTD4 and LTE4, as well as platelet activating factor. These products have deleterious effects on the airway tissue including mucosal and smooth muscle layers. Accumulating evidence suggests that these agents may also influence the accumulation and maintenance of eosinophilic responses at the site of inflammation. This article reviews the possible anti-inflammatory mode of action of these therapies. It also discusses where there may be a gap in the knowledge regarding the potential direct and indirect effects of LT modifiers on eosinophil function and recruitment.

Food and aeroallergens in eosinophilic esophagitis: role of the allergist in patient management.

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Aceves, Seema S

2014-07-01

Eosinophilic esophagitis is a clinicopathologic disease of increasing worldwide prevalence that is triggered by food antigens. The concurrent management of all of the atopic diseases affecting a single individual is likely to be important for successful long-term eosinophilic esophagitis management. This review covers the role of the allergist in eosinophilic esophagitis with a focus on the literature from the past 2  years. Studies in the past 2  years document that testing for immediate and delayed allergic hypersensitivity to foods can be of utility in building elimination diets in children, but that this may not be the case in adults. In addition, it has been shown that a number of cells and interleukins involved in Th2 inflammation such as invariant natural killer T cells, basophils, and interleukin-9 are important in eosinophilic esophagitis pathogenesis. Finally, the role of foods in generating esophageal remodeling has been shown using murine models. Recent studies support the role of the allergist in eosinophilic esophagitis management, especially for food allergen testing, interpretation, and the management of food allergies concurrent atopic diatheses. In addition, allergists have made significant research contributions in our understanding of eosinophilic esophagitis.

Human eosinophils - potential pharmacological model applied in human histamine H4 receptor research.

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Grosicki, Marek; Kieć-Kononowicz, Katarzyna

2015-01-01

Histamine and histamine receptors are well known for their immunomodulatory role in inflammation. In this review we describe the role of histamine and histamine H4 receptor on human eosinophils. In the first part of article we provide short summary of histamine and histamine receptors role in physiology and histamine related therapeutics used in clinics. We briefly describe the human histamine receptor H4 and its ligands, as well as human eosinophils. In the second part of the review we provide detailed description of known histamine effects on eosinophils including: intracellular calcium concentration flux, actin polymerization, cellular shape change, upregulation of adhesion proteins and cellular chemotaxis. We provide proofs that these effects are mainly connected with the activation of histamine H4 receptor. When examining experimental data we discuss the controversial results and limitations of the studies performed on isolated eosinophils. In conclusion we believe that studies on histamine H4 receptor on human eosinophils can provide interesting new biomarkers that can be used in clinical studies of histamine receptors, that in future might result in the development of new strategies in the treatment of chronic inflammatory conditions like asthma or allergy, in which eosinophils are involved.

Impaired esophageal motor function in eosinophilic esophagitis.

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Santander, Cecilio; Chavarría-Herbozo, Carlos M; Becerro-González, Irene; Burgos-Santamaría, Diego

2015-10-01

Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.

Genetics of Eosinophilic Esophagitis

Science.gov (United States)

2012-03-01

disease of the esophagus that affects at least 4 in 10,000 persons.1 Although symptomatically resembling gastroe - sophageal reflux disease, EE is...clinically defined as esophageal eosinophilia (>_15 intraepithelial eosinophils per high-powered field) in the absence of abnormal acid reflux disease...that distinguish eosin- ophilic esophagitis (EoE) from other inflammatory disorders, including gastroesophageal reflux disease (GERD). As the prev

Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

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Gudbjartsson, Daniel F; Bjornsdottir, Unnur S; Halapi, Eva

2009-01-01

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts.......2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated...

X-ray and CT findings of costal eosinophilic granuloma

International Nuclear Information System (INIS)

Tu Zhanhai; Lin Zhengyu; Chen Yiguang

2010-01-01

Objective: To study the X-ray and CT features of costal eosinophilic granuloma for a better understanding. Methods: Eight patients with costal eosinophilic granuloma proved by surgery or biopsy were analyzed retrospectively. All patients had X-ray plain film, 6 patients had CT examination, including a case of enhanced CT scan. Results: All 8 lesions were solitary. Six lesions were in the anterior rib and 2 in the posterior rib. On X-ray, all case showed single cavity and oval lesion with clear boundary. On CT images, 5 lesions demonstrated expansile destruction of bone with cortical bone thinning, and 3 were osteolystic destruction with soft tissue mass around. On the patient with enhanced CT scan, the lesions showed a moderate and uniform enhancement. Conclusion: The X-ray and CT findings of costal eosinophilic granuloma are characteristic. (authors)

Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs.

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Julie G Ledford

Full Text Available Surfactant protein-A (SP-A has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. In the current study, we used an in vivo model with wild type (WT and SP-A(-/- allergic mice challenged with the model antigen ovalbumin (Ova that were concurrently infected with Mp (Ova+Mp to test the hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products. SP-A deficient mice exhibit significant increases in inflammatory cells, mucus production and lung damage during concurrent allergic airway disease and infection (Ova+Mp as compared to the WT mice of the same treatment group. In contrast, SP-A deficient mice have significantly decreased Mp burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase (EPO, which has been implicated in pathogen killing and also in epithelial dysfunction due to oxidative damage of resident lung proteins, is enhanced in samples from allergic/infected SP-A(-/- mice as compared to WT mice. In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity. These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation

Scleroderma mimicker – Eosinophilic fasciitis

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Debanjali Sinha

2017-01-01

Full Text Available Eosinophilic fasciitis is an uncommon connective tissue disorder characterized by thickening of the deep fascia and overlying skin and subcutaneous tissue. It may mimic scleroderma and other scleroderma-like conditions. It may be a manifestation of paraneoplastic disorders or may be associated with hematological disorders including lymphomas. Definitive diagnosis is made on histological examination of a deep skin biopsy revealing thickened deep fascia and infiltration by lymphocytes and eosinophils. Enhancement of deep fascia on Gadolinium contrast-enhanced magnetic resonance imaging may be used as a substitute for skin biopsy. Ultrasound imaging is an evolving imaging tool for diagnosing it. Glucocorticoids with or without immunosuppressive agents remains the mainstay of therapy with good response, generally. A younger age of onset, morphea like lesions and dermal fibrosclerosis is more likely to be associated with the refractory disease. Early diagnosis and appropriate treatment may result in better outcomes in terms of morbidity and quality of life of the patients.

The Significance of Mast Cells and Eosinophils Counts in Surgically Resected Appendix

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Ashwini Kolur

2014-06-01

Materials and Methods: The material for study consisted of appendix specimens received for histopathological examination in the Department of pathology. A 5 year study was conducted, 3 years retrospective and 2 years prospective. Results: Out of 777 cases studied the incidence of appendicitis is high, in the first and second decades of life and slightly higher in females. Recurrent appendicitis was more common when compared to other inflamed appendices. Conclusions: Eosinophil counts in all the layers were very high in acute eosinophilic appendicitis compared to normal appendices. A higher mast cell count was seen in acute eosinophilic appendicitis and recurrent appendicitis. No correlation was found between mast cell and eosinophilic density. Our observations support the allergic theory of appendicitis rather than the obstructive theory. [J Interdiscipl Histopathol 2014; 2(3.000: 150-153

BLOOD EOSINOPHIL NUMBERS AND ACTIVITY DURING 24 HOURS - EFFECTS OF TREATMENT WITH BUDESONIDE AND BAMBUTEROL

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WEMPE, JB; TAMMELING, EP; KOETER, GH; HAKANSSON, L; VENGE, P; POSTMA, DS

1992-01-01

The effects of the inhaled corticosteroid budesonide and the oral long-acting beta-agonist bambuterol on circadian variation of blood eosinophil numbers, serum levels of eosinophil cationic protein (ECP), serum eosinophil chemotactic activity (ECA), and serum neutrophil chemotactic activity (NCA)

Association of Blood Eosinophil and Blood Neutrophil Counts with Asthma Exacerbations in the Copenhagen General Population Study

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Vedel-Krogh, Signe; Nielsen, Sune Fallgaard; Lange, Peter

2017-01-01

BACKGROUND: Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated...... with the risk of asthma exacerbations among individuals with asthma from the general population. METHODS: From the Copenhagen General Population Study with 81351 participants, we included 4838 with self-reported asthma. We recorded baseline blood eosinophil and neutrophil counts, and asthma exacerbations during...... with blood eosinophil counts >0.29 × 10(9)/L (highest tertile) vs individuals with blood eosinophil counts

Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma.

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Gaurav, Rohit; Bewtra, Againdra K; Agrawal, Devendra K

2015-08-01

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β- and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very low expression of NOX1, NOX3, and NOX5 and no NOX4 mRNA. The level of NOX2 mRNA transcripts increased with disease severity in the eosinophils of subjects with asthma compared with healthy nonatopic volunteers. Change in granularity and size in eosinophils, but no change in intracellular ROS, was observed with phorbol myristate acetate (PMA). PMA, TGF-β, and eotaxin used the CLC3-dependent pathway to increase superoxide radicals. TGF-β and eotaxin induced CLC3-dependent chemotaxis of eosinophils. These findings support the requirement of CLC3 in the activation and migration of human blood eosinophils and may provide a potential novel therapeutic target to regulate eosinophil hyperactivity in allergic airway inflammation in asthma.

A Pilot Study of Omalizumab in Eosinophilic Esophagitis

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Loizou, Denise; Enav, Benjamin; Komlodi-Pasztor, Edina; Hider, Pamela; Kim-Chang, Julie; Noonan, Laura; Taber, Tabitha; Kaushal, Suhasini; Limgala, Renuka; Brown, Margaret; Gupta, Raavi; Balba, Nader; Goker-Alpan, Ozlem; Khojah, Amer; Alpan, Oral

2015-01-01

Eosinophilic disorders of the gastrointestinal tract are an emerging subset of immune pathologies within the spectrum of allergic inflammation. Eosinophilic Esophagitis (EoE), once considered a rare disease, is increasing in incidence, with a rate of over 1 in 10,000 in the US, for unknown reasons. The clinical management of EoE is challenging, thus there is an urgent need for understanding the etiology and pathophysiology of this eosinophilic disease to develop better therapeutic approaches. In this open label, single arm, unblinded study, we evaluated the effects of an anti-IgE treatment, omalizumab, on local inflammation in the esophagus and clinical correlates in patients with EoE. Omalizumab was administered for 12 weeks to 15 subjects with long standing EoE. There were no serious side effects from the treatment. Esophageal tissue inflammation was assessed both before and after therapy. After 3 months on omalizumab, although tissue Immunoglobulin E (IgE) levels were significantly reduced in all but two of the subjects, we found that full remission of EoE, which is defined as histologic and clinical improvement only in 33% of the patients. The decrease in tryptase-positive cells and eosinophils correlated significantly with the clinical outcome as measured by improvement in endoscopy and symptom scores, respectively. Omalizumab-induced remission of EoE was limited to subjects with low peripheral blood absolute eosinophil counts. These findings demonstrate that in a subset of EoE patients, IgE plays a role in the pathophysiology of the disease and that anti-IgE therapy with omalizumab may result in disease remission. Since this study is open label there is the potential for bias, hence the need for a larger double blind placebo controlled study. The data presented in this pilot study provides a foundation for proper patient selection to maximize clinical efficacy. Trial Registration ClinicalTrials.gov NCT01040598 PMID:25789989

Case series of eosinophilic meningoencephalitis from South India

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Parameswaran K

2006-01-01

Full Text Available Eosinophilic meningoencephalitis (EM is a rare type of meningoencephalitis. The objective of this report is to describe a series of EM identified in a specific geographic area over a short period of time. Materials and Methods: This series of cases are described from a neurological center in Central Kerala occuring in the period between February 2004 and June 2006. Results: During this period we had identified ten patients (eight males and two females with EM. Their mean age was 37.1 years (range 15-60 years. Main symptomatologies were fever, severe headache, body pain, abdominal pain and arthralgia. One patient was in akinetic rigid state with coma. All patients had peripheral eosinophilia. The cerebrospinal fluid (CSF of all patients showed eosinophilic pleocytosis. The mean CSF white cell count was 588 cells. CSF differential count showed 50-70% eosinophils. CSF glucose levels were normal but proteins were markedly raised (mean CSF protein was 180 mg/dl. MRI brain showed T2 hyperintensities diffusely in periventricular white matter in the comatose patient. Contrast enhanced CT scan of the brain was normal in others. All eight male patients gave history of eating "raw flesh of Monitor Lizard" (Iguana some three to fourteen days prior to the onset of symptoms. There was no such history for the female patients. Considering the history of exposure and eosinophilic meningitis we suspected a meningoencephalitis with Angiostrongylus cantonensis and treated them with albendazole, steroid and other supportive measures. All of them recovered. Conclusion: Eosinophilic meningitis (EM is a rare condition and in this locality, a CNS infection with Agiostrongylus cantonensis is highly likely. AC is a parasite in monitor lizard. Human infection occurs from consumption of uncooked flesh or blood of infected lizards. Physicians need to maintain a high index of suspicion and enquire for any exposure to uncooked meat or blood of monitor lizard when faced with EM

Mucinous urothelial carcinoma of the renal pelvis

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Kemal Behzatoğlu

2014-12-01

Full Text Available Urothelial carcinoma with abundant myxoid stroma is a newly-described and extremely rare entity. Since only very few cases have been reported, there is no consensus on its nomenclature. Microscopic examination revealed invasive urothelial carcinoma with widespread low-grade noninvasive areas. There were focal invasive areas in the neighborhood of the renal parenchyma. Malignant urothelial tumor/cell groups localized in the stroma had abundant myxoid/mucinous background in the invasive areas. The cytoplasm of the tumoral cells was more eosinophilic in these areas and the cells formed small groups and cords. Histochemically, PAS and Alcian Blue were positive in the cytoplasm of the tumoral cells and in the stroma while negative in the non-mucinous areas. Immunohistochemically, the tumoral cells of the mucinous invasive areas diffusely expressed MUC1 and MUC2. We discuss the origin of the mucinous/myxoid stroma, the tumor’s nature and its nomenclature with histochemical and immunohistochemical features.

Genetics Home Reference: eosinophil peroxidase deficiency

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... play a role in regulating inflammation by fighting microbial invaders. EPX gene mutations reduce or prevent eosinophil ... GINA) Turns 10 All Bulletins Features What are genome editing and CRISPR-Cas9? What is direct-to- ...

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

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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

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. 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. 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. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

Eosinophils contribute to the resolution of lung-allergic responses following repeated allergen challenge.

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Takeda, Katsuyuki; Shiraishi, Yoshiki; Ashino, Shigeru; Han, Junyan; Jia, Yi; Wang, Meiqin; Lee, Nancy A; Lee, James J; Gelfand, Erwin W

2015-02-01

Eosinophils accumulate at the site of allergic inflammation and are critical effector cells in allergic diseases. Recent studies have also suggested a role for eosinophils in the resolution of inflammation. To determine the role of eosinophils in the resolution phase of the response to repeated allergen challenge. Eosinophil-deficient (PHIL) and wild-type (WT) littermates were sensitized and challenged to ovalbumin (OVA) 7 or 11 times. Airway inflammation, airway hyperresponsiveness (AHR) to inhaled methacholine, bronchoalveolar lavage (BAL) cytokine levels, and lung histology were monitored. Intracellular cytokine levels in BAL leukocytes were analyzed by flow cytometry. Groups of OVA-sensitized PHIL mice received bone marrow from WT or IL-10(-/-) donors 30 days before the OVA challenge. PHIL and WT mice developed similar levels of AHR and numbers of leukocytes and cytokine levels in BAL fluid after OVA sensitization and 7 airway challenges; no eosinophils were detected in the PHIL mice. Unlike WT mice, sensitized PHIL mice maintained AHR, lung inflammation, and increased levels of IL-4, IL-5, and IL-13 in BAL fluid after 11 challenges whereas IL-10 and TGF-β levels were decreased. Restoration of eosinophil numbers after injection of bone marrow from WT but not IL-10-deficient mice restored levels of IL-10 and TGF-β in BAL fluid as well as suppressed AHR and inflammation. Intracellular staining of BAL leukocytes revealed the capacity of eosinophils to produce IL-10. After repeated allergen challenge, eosinophils appeared not essential for the development of AHR and lung inflammation but contributed to the resolution of AHR and inflammation by producing IL-10. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue.

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Bolus, W Reid; Gutierrez, Dario A; Kennedy, Arion J; Anderson-Baucum, Emily K; Hasty, Alyssa H

2015-10-01

Adipose tissue (AT) inflammation during obesity is mediated by immune cells and closely correlates with systemic insulin resistance. In lean AT, eosinophils are present in low but significant numbers and capable of promoting alternative macrophage activation in an IL-4/IL-13-dependent manner. In WT mice, obesity causes the proportion of AT eosinophils to decline, concomitant with inflammation and classical activation of AT macrophages. In this study, we show that CCR2 deficiency leads to increased eosinophil accumulation in AT. Furthermore, in contrast to WT mice, the increase in eosinophils in CCR2(-/-) AT is sustained and even amplified during obesity. Interestingly, a significant portion of eosinophils is found in CLSs in AT of obese CCR2(-/-) mice, which is the first time eosinophils have been shown to localize to these inflammatory hot spots. CCR2(-/-) bone marrow precursors displayed increased expression of various key eosinophil genes during in vitro differentiation to eosinophils, suggesting a potentially altered eosinophil phenotype in the absence of CCR2. In addition, the proportion of eosinophils in AT positively correlated with local expression of Il5, a potent eosinophil stimulator. The increase in eosinophils in CCR2(-/-) mice was detected in all white fat pads analyzed and in the peritoneal cavity but not in bone marrow, blood, spleen, or liver. In AT of CCR2(-/-) mice, an increased eosinophil number positively correlated with M2-like macrophages, expression of the Treg marker Foxp3, and type 2 cytokines, Il4, Il5, and Il13. This is the first study to link CCR2 function with regulation of AT eosinophil accumulation. © Society for Leukocyte Biology.

Unfavorably Altered Fibrin Clot Properties in Patients with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Association with Thrombin Generation and Eosinophilia.

Science.gov (United States)

Mastalerz, Lucyna; Celińska-Lӧwenhoff, Magdalena; Krawiec, Piotr; Batko, Bogdan; Tłustochowicz, Witold; Undas, Anetta

2015-01-01

Given reports on the increased prevalence of thromboembolic incidents in patients with eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome), we investigated whether fibrin clot properties are unfavorably altered in EGPA. Ex vivo plasma fibrin clot characteristics, including clot permeability, turbidimetry and efficiency of fibrinolysis using two assays, were investigated in 34 consecutive patients with remission in EGPA according to the Birmingham Vasculitis Activity Score version 3 (23 female, 11 male), aged 48 (range, 21-80) years. The control group comprised 34 age- and sex- matched volunteers. Compared with controls, patients with EGPA were characterized by denser fiber clots (estimated pore size, Ks, 7.30±0.93 vs 10.14±1.07 10-9 cm2), faster fibrin polymerization (lag phase in a turbidimetric curve, 41.8±3.6 vs 47.4±2.9 s), thicker fibrin fibers (maximum absorbance, ΔAbs, 0.87±0.09 vs 0.72±0.07), higher maximum levels of D-dimer released from clots (DDmax 4.10±0.46 vs 3.54±0.35 mg/L), and prolonged clot lysis time (t50%; 9.50±1.45 vs 7.56±0.87 min); all p<0.0001. Scanning electron microscopy images confirmed denser plasma fibrin networks composed of thinner fibers formed in EGPA. Antineutrophil cytoplasmic antibody status and C-reactive protein did not affect clot variables. Multivariate analysis adjusted for fibrinogen showed that Ks was predicted by eosinophil count, peak thrombin generation, factor VIII, and soluble CD40 ligand, whereas eosinophil count, peak thrombin generation and antiplasmin predicted t50%. This study is the first to show that EGPA is associated with prothrombotic plasma fibrin clot phenotype, which may contribute to thromboembolic manifestations reported in this disease.

Unfavorably Altered Fibrin Clot Properties in Patients with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome: Association with Thrombin Generation and Eosinophilia.

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Lucyna Mastalerz

Full Text Available Given reports on the increased prevalence of thromboembolic incidents in patients with eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome, we investigated whether fibrin clot properties are unfavorably altered in EGPA.Ex vivo plasma fibrin clot characteristics, including clot permeability, turbidimetry and efficiency of fibrinolysis using two assays, were investigated in 34 consecutive patients with remission in EGPA according to the Birmingham Vasculitis Activity Score version 3 (23 female, 11 male, aged 48 (range, 21-80 years. The control group comprised 34 age- and sex- matched volunteers.Compared with controls, patients with EGPA were characterized by denser fiber clots (estimated pore size, Ks, 7.30±0.93 vs 10.14±1.07 10-9 cm2, faster fibrin polymerization (lag phase in a turbidimetric curve, 41.8±3.6 vs 47.4±2.9 s, thicker fibrin fibers (maximum absorbance, ΔAbs, 0.87±0.09 vs 0.72±0.07, higher maximum levels of D-dimer released from clots (DDmax 4.10±0.46 vs 3.54±0.35 mg/L, and prolonged clot lysis time (t50%; 9.50±1.45 vs 7.56±0.87 min; all p<0.0001. Scanning electron microscopy images confirmed denser plasma fibrin networks composed of thinner fibers formed in EGPA. Antineutrophil cytoplasmic antibody status and C-reactive protein did not affect clot variables. Multivariate analysis adjusted for fibrinogen showed that Ks was predicted by eosinophil count, peak thrombin generation, factor VIII, and soluble CD40 ligand, whereas eosinophil count, peak thrombin generation and antiplasmin predicted t50%.This study is the first to show that EGPA is associated with prothrombotic plasma fibrin clot phenotype, which may contribute to thromboembolic manifestations reported in this disease.

Activated Eosinophils are Present in Esophageal Muscle in Patients with Achalasia of the Esophagus

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Jin, Hong; Wang, Bin; Zhang, Li-li

2018-01-01

Background The aim of this study was to undertake a histological evaluation of the presence of eosinophils in esophageal muscle in patients with achalasia before treatment with peroral endoscopic myotomy (POEM), with clinical follow-up at one year. Material/Methods Before treatment, esophageal biopsies including mucosa and esophageal muscle were obtained from 28 patients with achalasia. Nine patients who had undergone esophagectomy for esophageal carcinoma were included in the control group. The Eckardt Score was used to evaluate the clinical symptoms of achalasia. Histology of routinely processed tissue sections was used to perform eosinophil cell counts (0 to +++), and immunohistochemistry was used to detect expression of eosinophil major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and S100 protein in cases of achalasia (n=28) and controls (n=9). The findings in patients with achalasia were compared before and one year following POEM. Results Esophageal tissue from patients with achalasia showed eosinophils infiltrating into the muscularis externa in 85.7% (24/28), into the muscularis propria in 28.6% (8/28), and in 89% (25/28) there were few remaining myenteric ganglion cells, before POEM. The extent of inflammation was similar in all regions of the esophagus and between subtypes of achalasia. At one year following POEM, the Eckardt Scores between the former eosinophil (0) group and the eosinophil (+++) group were significantly different (Z=3.50, P=0.030). Conclusions Achalasia of the esophagus was associated with infiltration of the esophageal muscle by activated eosinophils and a decrease in the density of ganglion cells in the myenteric esophageal plexus. PMID:29672471

Mechanisms for cytoplasmic organization: an overview.

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Pagliaro, L

2000-01-01

One of the basic characteristics of life is the intrinsic organization of cytoplasm, yet we know surprisingly little about the manner in which cytoplasmic macromolecules are arranged. It is clear that cytoplasm is not the homogeneous "soup" it was once envisioned to be, but a comprehensive model for cytoplasmic organization is not available in modern cell biology. The premise of this volume is that phase separation in cytoplasm may play a role in organization at the subcellular level. Other mechanisms for non-membrane-bounded intracellular organization have previously been proposed. Some of these will be reviewed in this chapter. Multiple mechanisms, involving phase separation, specific intracellular targeting, formation of macromolecular complexes, and channeling, all could well contribute to cytoplasmic organization. Temporal and spatial organization, as well as composition, are likely to be important in defining the characteristics of cytoplasm.

Imaginal diagnosis of eosinophilic granuloma of long bones

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Cui Fa; Cui Minyi

2006-01-01

Objective: To analyze the clinical and imaging features of eosinophilic granuloma of long bones so as to improve diagnosis accuracy of the disease. Methods: The clinic materials and imaging findings of 24 patients with eosinophilic granuloma of long bones proved by surgery or histopathology were analyzed retrospectively. All the patients received radiography; CT scan was performed in 6 cases; and MRI was done in 4 cases. Results: Fifteen patients out of 24 were male and 9 were female, with the average age 14. 7 years old. Solitary lesion was found in 22 cases, and multiple bone destruction was noted in 2 cases. There were 14 lesions located in femur; 5 in tibia; 3 in humer; and 2 in fibula. In total 16 lesions involved diaphysis and in 8 cases the metaphysis was invaded. Bone destruction, the changes of the adjacent cortex, periosteal reaction and soft tissue mass or swelling were demonstrated in images obtained. Conclusion: The imaging features in eosinophilic granuloma of long bones are characteristic. Careful and integrative analysis of imaging findings improves diagnosis accuracy of the disease. (authors)

The role of the eosinophil-selective chemokine, eotaxin, in allergic and non-allergic airways inflammation

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Conroy Dolores M

1997-01-01

Full Text Available Blood eosinophilia and tissue infiltration by eosinophils are frequently observed in allergic inflammation and parasitic infections. This selective accumulation of eosinophils suggested the existence of endogenous eosinophil-selective chemoattractants. We have recently discovered a novel eosinophil-selective chemoattractant which we called eotaxin in an animal model of allergic airways disease. Eotaxin is generated in both allergic and non-allergic bronchopulmonary inflammation. The early increase in eotaxin paralled eosinophil infiltration in the lung tissue in both models. An antibody to IL-5 suppressed lung eosinophilia, correlating with an inhibition of eosinophil release from bone marrow, without affecting eotaxin generation. This suggests that endogenous IL-5 is important for eosinophil migration but does not appear to be a stimulus for eotaxin production. Constitutive levels of eotaxin observed in guinea-pig lung may be responsible for the basal lung eosinophilia observed in this species. Allergen-induced eotaxin was present mainly in the epithelium and alveolar macrophages, as detected by immunostaining. In contrast there was no upregulation of eotaxin by the epithelial cells following the injection of Sephadex beads and the alveolar macrophage and mononuclear cells surrounding the granuloma were the predominant positive staining cells. Eotaxin and related chemokines acting through the CCR3 receptor may play a major role in eosinophil recruitment in allergic inflammation and parasitic diseases and thus offer an attractive target for therapeutic intervention.

Eosinophils, pruritus and psoriasis: effects of treatment with etretinate or cyclosporin-A.

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Schopf, R E; Hultsch, T; Lotz, J; Bräutigam, M

1998-11-01

The antipsoriatic drugs cyclosporin A (CyA) and etretinate have been found to influence proinflammatory eosinophilic leukocytes and pruritus. We compared the number of blood eosinophils, concentration of serum eosinophil cationic protein (ECP), and pruritus in patients with psoriasis treated with either CyA or etretinate. Patients with psoriasis vulgaris were randomly assigned to treatment for 10 weeks with either CyA (n = 21) or etretinate (n = 10). The psoriasis area-and-severity index (PASI-score) and pruritus (according to a 0-3 scale) served as clinical parameters, the blood esosinophil counts (Coulter Counter) and the serum ECP (RIA, Pharmacia) as laboratory parameters. After CyA treatment the PASI-score amounted to 24 +/- 4%, after etretinate to 56 +/- 6% of the initial values (mean +/- SEM). One week after CyA treatment, esosinophils dropped from 190 +/- 21 to 137 +/- 16/microliter (P = 0.038, Wilcoxon test), after 10 weeks to 127 +/- 18/microliter (P = 0.006). By contrast, under etretinate blood eosinophil counts only changed marginally. Before treatment, ECP concentrations of 15.71 +/- 1.30 (CyA) and 15.3 +/- 5.53 micrograms/l (etretinate) were measured (normal range 3-16 micrograms/l), ECP remained constant under both CyA and etretinate or tended to increase after 10 weeks; about 50% of the patients exhibited elevated ECP concentrations. Pruritus diminished more with CyA than etretinate therapy. PASI-scores and pruritus were directly proportional. We conclude that treatment of psoriasis with CyA leads to a rapid drop of blood eosinophils and that the activation state of eosinophils does not decrease after antipsoriatic treatment. Pruritus in psoriasis is coupled to disease severity. The underlying antipsoriatic mechanisms of CyA may be linked to lowering the number of blood eosinophils.

Eosinophilic Gastroenteritis Presenting as Intestinal Obstruction - A Case Series

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Amita Krishnappa

2011-07-01

Full Text Available Eosinophilic Gastroenteritis is a rare disease characterized by infiltration of the gastrointestinal tract by an increased number of eosinophils as compared to the normal. The anatomic location and intensity of the infiltrate decides the varied clinical symptomatology with which these patients present. The present report deals with four cases, all presenting with clinical signs of intestinal obstruction A laparotomy performed revealed a stricture in the first case, superficial ulcers and adhesions in the second case, an ileocaecal mass in the third case and volvulus formation in the fourth case. Eosinophilic gastroenteritis was confirmed on histopathology in all the four cases. All the four patients experienced relief of symptoms after resection. It is essential to diagnose the disease to differentiate it from other conditions presenting as intestinal obstruction. The cases are presented because of the rarity of occurrence and presentation. Relevant literature has been reviewed.

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

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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. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Impaired esophageal motor function in eosinophilic esophagitis

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Cecilio Santander

2015-10-01

Full Text Available Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.

High resolution autoradiographic studies of RNA, protein and DNA synthesis during human eosinophil granulocytopoiesis

International Nuclear Information System (INIS)

Wickramasinghe, S.N.; Hughes, M.

1978-01-01

Human bone marrow cells which had been incubated with [ 3 H] uridine or [ 3 H]leucine for 1 h were studied using the technique of electron microscope-autoradiography. The autoradiographs revealed the presence of newly-synthesized RNA and protein molecules within or on a proportion of (1) the primary and secondary granules in all classes of eosinophil precursors and (2) the secondary granules in eosinophil granulocytes. It is suggested that the granule-associated RNA molecules may be concerned with the synthesis of at least some of the new protein molecules which were incorporated into the limiting membrane or substance of eosinophil granules long after the immature primary granule stage. Studies of eosinophil precursors which had been incubated with [ 3 H]thymidine for 1 h showed that the eosinophil granules did not label with this DNA precursor. (author)

Non-Eosinophilic Nasal Polyps Shows Increased Epithelial Proliferation and Localized Disease Pattern in the Early Stage.

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Dong-Kyu Kim

Full Text Available Non-eosinophilic nasal polyps (NPs show less inflammatory changes and are less commonly associated with lower airway inflammatory disorders such as asthma, compared with eosinophilic NPs. However, the development of non-eosinophilic NPs which is a predominant subtype in Asian population still remains unclear.A total of 81 patients (45 with non-eosinophilic NPs and 36 with eosinophilic NPs were enrolled. Clinical information and computed tomography (CT, endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE levels and for mRNA expression levels of interleukin (IL-4, IL-5, IL-13, interferon (IFN-γ, tumor necrosis factor (TNF-α, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF-β1, TGF-β2, TGF-β3, and periostin. Immunostaining assessment of Ki-67 as a proliferation marker was performed.We found that epithelial in-growing patterns such as pseudocysts were more frequently observed in histological and endoscopic evaluations of non-eosinophilic NPs, which was linked to increase epithelial staining of Ki-67, a proliferating marker. Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs. To investigate the developmental course of each subtype, CT was analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more localized pattern and maxillary sinus involvement, but lesser olfactory involvement in early stage whereas eosinophilic NPs were characterized by diffuse ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M CT scores, indicating ethmoidal dominant involvement, were one of surrogate markers for eosinophilic NP. E/M CT scores was positively correlated with levels of TH2 inflammatory markers, including IL-4, IL-5, periostin mRNA expression and total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- γ were inversely correlated. Moreover, if the combinatorial algorithm meet the three

Suppressive effects of primed eosinophils on single epicutaneous sensitization through regulation of dermal dendritic cells.

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Lin, Jing-Yi; Ta, Yng-Cun; Liu, I-Lin; Chen, Hsi-Wen; Wang, Li-Fang

2016-07-01

Eosinophils are multifunctional innate immune cells involved in many aspects of innate and adaptive immunity. Epicutaneous sensitization with protein allergen is an important sensitization route for atopic dermatitis. In this study, using a murine single protein-patch model, we show that eosinophils of a primed status accumulate in draining lymph nodes following single epicutaneous sensitization. Further, depletion of eosinophils results in enhancement of the induced Th1/Th2 immune responses, whereas IL-5-induced hypereosinophilia suppresses these responses. Mechanistically, primed eosinophils cause a reduction in the numbers and activation status of dermal dendritic cells in draining lymph nodes. Collectively, these results demonstrate that primed eosinophils exert suppressive effects on single epicutaneous sensitization through regulation of dermal dendritic cells. Thus, these findings highlight the critical roles of eosinophils in the pathogenesis of atopic dermatitis with important clinical implications for the prevention of allergen sensitization. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eosinophilic Angiocentric Fibrosis of the Nasal Septum

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Yunchuan Li

2013-01-01

Full Text Available 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.

A pediatric case of Fascioliasis with eosinophilic pneumonia.

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Bayhan, Gülsüm İclal; Batur, Abdulsamet; Taylan-Özkan, Ayşegül; Demirören, Kaan; Beyhan, Yunus Emre

2016-01-01

Fasciolia spp. are common trematode infestations worldwide. Fasciolia spp. may lead to hepatic diseases in the acute phase and may cause biliary diseases in the chronic phase. In addition, Fasciolia spp. may rarely cause extrahepatic signs and symptoms. The clinical manifestations of fascioliasis are divided into three groups: typical, atypical, and ectopic. Eosinophilic pneumonia is an atypical presentation of acute fascioliasis and it has been reported very rarely. Herein, we report a boy with marked blood eosinophilia and eosinophilic pneumonia who was diagnosed with fascioliasis by serologic tests and abdominal USG. The patient recovered completely following triclabendazole treatment.

Eosinophils promote generation and maintenance of immunoglobulin-A-expressing plasma cells and contribute to gut immune homeostasis.

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Chu, Van Trung; Beller, Alexander; Rausch, Sebastian; Strandmark, Julia; Zänker, Michael; Arbach, Olga; Kruglov, Andrey; Berek, Claudia

2014-04-17

Although in normal lamina propria (LP) large numbers of eosinophils are present, little is known about their role in mucosal immunity at steady state. Here we show that eosinophils are needed to maintain immune homeostasis in gut-associated tissues. By using eosinophil-deficient ΔdblGATA-1 and PHIL mice or an eosinophil-specific depletion model, we found a reduction in immunoglobulin A(+) (IgA(+)) plasma cell numbers and in secreted IgA. Eosinophil-deficient mice also showed defects in the intestinal mucous shield and alterations in microbiota composition in the gut lumen. In addition, TGF-β-dependent events including class switching to IgA in Peyer's patches (PP), the formation of CD103(+) T cells including Foxp3(+) regulatory (Treg), and also CD103(+) dendritic cells were disturbed. In vitro cultures showed that eosinophils produce factors that promote T-independent IgA class switching. Our findings show that eosinophils are important players for immune homeostasis in gut-associated tissues and add to data suggesting that eosinophils can promote tissue integrity. Copyright © 2014 Elsevier Inc. All rights reserved.

Increased Activity and Apoptosis of Eosinophils in Blister Fluids, Skin and Peripheral Blood of Patients with Bullous Pemphigoid.

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Engmann, Judith; Rüdrich, Urda; Behrens, Georg; Papakonstantinou, Eleni; Gehring, Manuela; Kapp, Alexander; Raap, Ulrike

2017-04-06

Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more common in elderly individuals. The aim of this study was to determine the functional activity of eosinophils in patients with BP compared with healthy donors. Blood, skin and blister-derived eosinophils were strongly activated in patients with BP, seen by increased surface expression of CD69 compared with controls. CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1×106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1α in BP blister fluids. Apoptosis in cultivated BP eosinophils was increased and accompanied by enhanced surface externalization of CD95. Caspase 3 positive eosinophils in lesional BP skin and blister fluid also showed the initiation of apoptosis. These results reveal novel pathophysiological aspects of BP, with a strong activation pattern and increased apoptosis of eosinophils in the peripheral blood, skin and blister fluids.

Anti-IL-5 attenuates activation and surface density of β2-integrins on circulating eosinophils after segmental antigen challenge

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Johansson, Mats W.; Gunderson, Kristin A.; Kelly, Elizabeth A. B.; Denlinger, Loren C.; Jarjour, Nizar N.; Mosher, Deane F.

2013-01-01

Background IL-5 activates αMβ2 integrin on blood eosinophils in vitro. Eosinophils in bronchoalveolar lavage (BAL) following segmental antigen challenge have activated β2-integrins. Objective To identify roles for IL-5 in regulating human eosinophil integrins in vivo. Methods Blood and BAL eosinophils were analyzed by flow cytometry in ten subjects with allergic asthma who underwent a segmental antigen challenge protocol before and after anti-IL-5 administration. Results Blood eosinophil reactivity with monoclonal antibody (mAb) KIM-127, which recognizes partially activated β2-integrins, was decreased after anti-IL-5. Before anti-IL-5, surface densities of blood eosinophil β2, αM, and αL integrin subunits increased modestly post-challenge. After anti-IL-5, such increases did not occur. Before or after anti-IL-5, surface densities of β2,αM, αL, and αD and reactivity with KIM-127 and mAb CBRM1/5, which recognizes high-activity αMβ2, were similarly high on BAL eosinophils 48 h post-challenge. Density and activation state of β1-integrins on blood and BAL eosinophils were not impacted by anti-IL-5, even though anti-IL-5 ablated a modest post-challenge increase on blood or BAL eosinophils of P-selectin glycoprotein ligand-1 (PSGL-1), a receptor for P-selectin that causes activation of β1-integrins. Forward scatter of blood eosinophils post-challenge was less heterogeneous and on the average decreased after anti-IL-5; however, anti-IL-5 had no effect on the decreased forward scatter of eosinophils in post-challenge BAL compared to eosinophils in blood. Blood eosinophil KIM-127 reactivity at the time of challenge correlated with the percentage of eosinophils in BAL post-challenge. Conclusion and Clinical Relevance IL-5 supports a heterogeneous population of circulating eosinophils with partially activated β2-integrins and is responsible for upregulation of β2-integrins and PSGL-1 on circulating eosinophils following segmental antigen challenge but has

The effects of Strongylus vulgaris parasitism on eosinophil distribution and accumulation in equine large intestinal mucosa.

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Rötting, A K; Freeman, D E; Constable, P D; Moore, R M; Eurell, J C; Wallig, M A; Hubert, J D

2008-06-01

Eosinophilic granulocytes have been associated with parasite or immune-mediated diseases, but their functions in other disease processes remain unclear. Cause and timing of eosinophil migration into the equine gastrointestinal mucosa are also unknown. To determine the effects of intestinal parasitism on eosinophils in equine large intestinal mucosa. Large intestinal mucosal samples were collected from horses and ponies (n = 16) from the general veterinary hospital population, ponies (n = 3) raised in a parasite-free environment, ponies experimentally infected with 500 infective Strongylus vulgaris larvae and treated with a proprietary anthelmintic drug (n = 14), and a similar group of ponies (n = 7) that received no anthelmintic treatment. Total eosinophil counts and eosinophil distribution in the mucosa were determined by histological examination. A mixed model analysis was performed and appropriate Bonferroni adjusted P values used for each family of comparisons. Pvulgaris and those raised in a parasite-free environment. Experimental infection with S. vulgaris, with or without subsequent anthelmintic treatment, did not change eosinophil counts, and counts were similar to those for horses from the general population. Migration of eosinophils to the equine large intestinal mucosa appears to be independent of exposure to parasites. Large intestinal mucosal eosinophils may have more functions in addition to their role in defence against parasites.

Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

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Konno, Yasunori; Ueki, Shigeharu; Takeda, Masahide; Kobayashi, Yoshiki; Tamaki, Mami; Moritoki, Yuki; Oyamada, Hajime; Itoga, Masamichi; Kayaba, Hiroyuki; Omokawa, Ayumi; Hirokawa, Makoto

2015-01-01

Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

Eosinophils Regulate Interferon Alpha Production in Plasmacytoid Dendritic Cells Stimulated with Components of Neutrophil Extracellular Traps.

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Skrzeczynska-Moncznik, Joanna; Zabieglo, Katarzyna; Bossowski, Jozef P; Osiecka, Oktawia; Wlodarczyk, Agnieszka; Kapinska-Mrowiecka, Monika; Kwitniewski, Mateusz; Majewski, Pawel; Dubin, Adam; Cichy, Joanna

2017-03-01

Eosinophils constitute an important component of helminth immunity and are not only associated with various allergies but are also linked to autoinflammatory disorders, including the skin disease psoriasis. Here we demonstrate the functional relationship between eosinophils and plasmacytoid dendritic cells (pDCs) as related to skin diseases. We previously showed that pDCs colocalize with neutrophil extracellular traps (NETs) in psoriatic skin. Here we demonstrate that eosinophils are found in psoriatic skin near neutrophils and NETs, suggesting that pDC responses can be regulated by eosinophils. Eosinophils inhibited pDC function in vitro through a mechanism that did not involve cell contact but depended on soluble factors. In pDCs stimulated by specific NET components, eosinophil-conditioned media attenuated the production of interferon α (IFNα) but did not affect the maturation of pDCs as evidenced by the unaltered expression of the costimulatory molecules CD80 and CD86. As pDCs and IFNα play a key role in autoimmune skin inflammation, these data suggest that eosinophils may influence autoinflammatory responses through their impact on the production of IFNα by pDCs.

Clinical and histopathological differential diagnosis of eosinophilic pustular folliculitis.

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Fujiyama, Toshiharu; Tokura, Yoshiki

2013-06-01

Eosinophilic pustular folliculitis (EPF) is an inflammatory disease characterized by repeated pruritic follicular papules and pustules arranged in arcuate plaques, and folliculotropic infiltration of eosinophils. The diagnosis of EPF is occasionally difficult and problematic because EPF may share the clinical appearance and histological findings with other diseases. Moreover, EPF has several clinical subtypes, including the classical type, infantile type and immunosuppression-associated type. Because the therapies of EPF are relatively specific as compared to eczematous disorders, accurate diagnosis is essential for the management of EPF. Clinical differential diagnoses include tinea, acne, rosacea, eczematous dermatitis, granuloma faciale, autoimmune annular erythema, infestations and pustular dermatosis. Histologically, cutaneous diseases with eosinophilic infiltrates can be differentially diagnosed. Follicular mucinosis, mycosis fungoides and other cutaneous T-cell lymphomas are the most important differential diagnoses both clinically and histopathologically. It should be kept in mind particularly that the initial lesions of cutaneous T-cell lymphoma resemble EPF. © 2013 Japanese Dermatological Association.

Eosinophil Resistance to Glucocorticoid-Induced Apoptosis is Mediated by the Transcription Factor NFIL3

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Pazdrak, Konrad; Moon, Young; Straub, Christof; Stafford, Susan; Kurosky, Alexander

2016-01-01

The mainstay of asthma therapy, glucocorticoids (GCs) exert their therapeutic effects through the inhibition of inflammatory signaling and induction of eosinophil apoptosis. However, laboratory and clinical observations of GC-resistant asthma suggest that GCs' effects on eosinophil viability may depend on the state of eosinophil activation. In the present study we demonstrate that eosinophils stimulated with IL-5 show impaired prop-aptoptotic response to GCs. We sought to determine the contribution of GC-mediated transactivating (TA) and transrepressing (TR) pathways in modulation of activated eosinophils' response to GC by comparing their response to the selective GC receptor (GR) agonist Compound A (CpdA) devoid of TA activity to that upon treatment with Dexamethasone (Dex). IL-5-activated eosinophils showed contrasting responses to CpdA and Dex, as IL-5-treated eosinophils showed no increase in apoptosis compared to cells treated with Dex alone, while CpdA elicited an apoptotic response regardless of IL-5 stimulation. Proteomic analysis revealed that both Nuclear Factor IL-3 (NFIL3) and Map Kinase Phosphatase 1 (MKP1) were inducible by IL-5 and enhanced by Dex; however, CpdA had no effect on NFIL3 and MKP1 expression. We found that inhibiting NFIL3 with specific siRNA or by blocking the IL-5-inducible Pim-1 kinase abrogated the protective effect of IL-5 on Dex-induced apoptosis, indicating crosstalk between IL-5 anti-apoptotic pathways and GR-mediated TA signaling occurring via the NFIL3 molecule. Collectively, these results indicate that 1) GCs' TA pathway may support eosinophil viability in IL-5-stimulated cells through synergistic upregulation of NFIL3; and 2) functional inhibition of IL-5 signaling (anti-Pim1) or the use of selective GR agonists that don't upregulate NFIL3 may be effective strategies for the restoring pro-apoptotic effect of GCs on IL-5-activated eosinophils. PMID:26880402

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

DEFF Research Database (Denmark)

Schratl, Petra; Royer, Julia F; Kostenis, Evi

2007-01-01

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......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...

Eosinophilic meningitis caused by infection of Angiostrongylus cantonensis in a traveler

Institute of Scientific and Technical Information of China (English)

GUAN Hongzhi; HOI Chupeng; CUI Liying; CHEN Lin

2013-01-01

A 55 - year - old female traveler returning from South China with acute onset of meningitis, presenting with eosinophilic pleocytosis in the cerebrospinal fluid was reported. The etiological diagnosis of angiostrongyliasis was confirmed by detection of specific serum antibody against Angiostrongylus cantonensis. Angiostrongyliasis should be considered as a major differential diagnosis for eosinophilic meningitis in the travelers to endemic regions.

Saiboku-to, a Kampo herbal medicine, inhibits LTC4 release from eosinophils

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Koichi Hirai

1998-01-01

Full Text Available Saiboku-to (TJ-96, a traditional Kampo herbal formation, has been used in the treatment of bronchial asthma in Japan as an anti-allergy herbal medicine. We investigated the effect of TJ-96 on leukotriene (LTC4 release from eosinophils and basophils isolated from healthy volunteers. Pre-incubation of eosinophils with TJ-96 inhibited ionophore- or formyl-methionyl-leucyl-phenylalanine (FMLP-induced LTC4 generation by eosinophils in a dose-dependent fashion. The TJ-96 was more potent in the release by ionophore (IC50 = 60 mg/mL than the release induced by FMLP (IC50 = 300 mg/mL. Maximal inhibition was observed when eosinophils were pretreated with TJ-96 for 5 min. Although TJ-96 at high concentrations inhibited IgE-mediated histamine release from human basophils, inhibition of IgE-mediated LTC4 release was not statistically significant. The potent inhibitory activity was found in the extract of Glycyrrhiza root, one of the herbal components of TJ-96, but the inhibitory effects were not due to either glycyrrhizin or liquiritin, the main elements of the Glycyrrhiza root. These results raise the possibility that the clinical efficacy of TJ-96 is derived, at least in part, from its potent inhibitory effect on LTC4 release from eosinophils.

Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy

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Melo, Rossana C.N., E-mail: rossana.melo@ufjf.edu.br [Laboratory of Cellular Biology, Department of Biology, ICB, Federal University of Juiz de Fora, UFJF, Rua José Lourenço Kelmer, Juiz de Fora, MG 36036-900 (Brazil); Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215 (United States); Weller, Peter F. [Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215 (United States)

2016-10-01

Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles – EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. - Highlights: • Application of EM to understand the complex secretory pathway in human eosinophils. • EM techniques reveal an active vesicular system associated with secretory granules. • Tubular vesicles are involved in the transport of granule-derived immune mediators.

Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy

International Nuclear Information System (INIS)

Melo, Rossana C.N.; Weller, Peter F.

2016-01-01

Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles – EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. - Highlights: • Application of EM to understand the complex secretory pathway in human eosinophils. • EM techniques reveal an active vesicular system associated with secretory granules. • Tubular vesicles are involved in the transport of granule-derived immune mediators.

Predictive value of eosinophils and neutrophils on clinical effects of ICS in COPD

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Hartjes, Floor J; Vonk, Judith M; Faiz, Alen

2018-01-01

BACKGROUND AND OBJECTIVE: Inflammation is present to a variable degree and composition in patients with COPD. This study investigates associations between both eosinophils and neutrophils in blood, sputum, airway wall biopsies and bronchoalveolar lavage (BAL) and their potential use as biomarkers...... and BAL were evaluated at baseline. In addition, at baseline, 6 and 30 months, forced expiratory flow in 1 s (FEV1 ), residual volume/total lung capacity (hyperinflation) and Clinical COPD Questionnaire were evaluated. RESULTS: Cross-sectional analyses at baseline showed that higher blood eosinophils were...... significantly associated with higher eosinophil counts in sputum, biopsies and BAL. However, blood neutrophils did not significantly correlate with neutrophil counts in the other compartments. Baseline eosinophils and neutrophils, in whichever compartment measured, did not predict longitudinal FEV1 changes...

Blood eosinophil counts for the prediction of the severity of exercise-induced bronchospasm in asthma.

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Koh, Y I; Choi, S

2002-02-01

It has been suggested that airway eosinophilic inflammation is associated with the severity of exercise-induced bronchospasm (EIB). Blood eosinophils are known to be an indirect marker of airway inflammation in asthma. The aim of this study is to investigate that a simple and easy blood test for blood eosinphil counts may predict the severity of EIB in asthma. Seventy-seven men with perennial asthma (age range 18-23 years) were included. Lung function test, skin prick test, and blood tests for eosinophils counts and total IgE levels were performed. Methacholine bronchial provocation test and, 24 h later, free running test were carried out. EIB was defined as a 15% reduction or more in post-exercise FEV1 compared with pre-exercise FEV1 value. Atopy score was defined as a sum of mean wheal diameters to allergens. EIB was observed in 60 (78%) of 77 subjects. Asthmatics with EIB showed significantly increased percentages of eosinophils (P 700 microl(-1) (36.9 +/- 12.7%) had significantly greater maximal % fall in FEV1 after exercise than asthmatics with eosinophils of 350 microl(-1) yielded the specificity of 88% and positive predictive value of 93% for the presence of EIB. When a multiple regression analysis of maximal % fall in FEV1 according to log eosinophil counts, log PC20, log IgE and atopy score was performed, only blood eosinophil counts were significant factor contributing to the maximal % fall in FEV1 after exercise. These findings not only suggest that a simple blood test for eosinophils may be useful in the prediction of the severity of EIB, but also reinforce the view that airway eosinophilic inflammation may play a major role in EIB in asthma.

Cutting Edge: Eosinophils Undergo Caspase-1-Mediated Pyroptosis in Response to Necrotic Liver Cells.

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Palacios-Macapagal, Daphne; Connor, Jane; Mustelin, Tomas; Ramalingam, Thirumalai R; Wynn, Thomas A; Davidson, Todd S

2017-08-01

Many chronic liver disorders are characterized by dysregulated immune responses and hepatocyte death. We used an in vivo model to study the immune response to necrotic liver injury and found that necrotic liver cells induced eosinophil recruitment. Necrotic liver induced eosinophil IL-1β and IL-18 secretion, degranulation, and cell death. Caspase-1 inhibitors blocked all of these responses. Caspase-1-mediated cell death with accompanying cytokine release is the hallmark of a novel form of cell death termed pyroptosis. To confirm this response in a disease model, we isolated eosinophils from the livers of Schistosoma mansoni -infected mice. S. mansoni eggs lodge in the hepatic sinusoids of infected mice, resulting in hepatocyte death, inflammation, and progressive liver fibrosis. This response is typified by massive eosinophilia, and we were able to confirm pyroptosis in the infiltrating eosinophils. This demonstrated that pyroptosis is a cellular pathway used by eosinophils in response to large-scale hepatic cell death. Copyright © 2017 by The American Association of Immunologists, Inc.

Pre-operative irradiation of eosinophilic granuloma in the parotid area

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Kitahara, Satoshi; Toda, Yukio; Nakajima, Hisami; Takeyama, Isamu; Sodemoto, Yukio; Endo, Masaru

1983-01-01

Eosinophilic granuloma is thought to originate in the reticuloendothelial system and cannot clearly be distinguished from the surrounding tissue during operation. An eosinophilic granuloma in the parotid area was removed after 25 days of irradiation at a dosage of 10.0 Gy per 3 days. A thin capsule of connective tissue was observed after the tumor was cut in half. Then, histopathological studies were performed on this connective tissue to determine the effect of the irradiation. Histopathologically, at the periphery of the tissue, atrophy of lymphocytes and destruction of the lymphoid tissue, which were thought to result in an increase in the connective tissue, were observed. It was concluded that a small dose of pre-operative radiation on eosinophilic granuloma in the parotid area made the tumor small and produced a capsule around the tumor. (author)

Case report 342: Eosinophilic granuloma of the right iliac wing

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Schlesinger, A.E.; Glass, R.B.J.; Fernbach, S.K.; Young, S.

1986-01-01

In summary, this case demonstrates that eosinophilic granuloma may present with findings on CT usually associated with aggressive malignant lesions, while plain films may show the same lesion to have the unequivocal appearance of a benign lesion. It is important, therefore, that eosinophilic granuloma be considered in the differential diagnosis of solitary bone lesions with extraosseous extension, extensive destruction of the cortex and associated periosteal reaction. A local biopsy, as opposed to wide excision, should be performed for diagnosis, prior to any therapy. Of at least equal significance, it is obvious from this case that plain films in many instances still maintain their importance and with few exceptions should be obtained prior to the CT study. In this instance the diagnosis of a benign disorder and even the specific diagnoses of eosinophilic, granuloma was suggested with confidence because of the plain films. (orig.)

Idiopathic eosinophilic parotitis in an eight-year-old boy: a case report

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Gelardi Matteo

2011-08-01

Full Text Available Abstract Introduction A number of medical conditions, some of them recently reported, are associated with an increased production of eosinophils. We report the first case of eosinophilic parotitis in the literature. Case presentation The patient was an eight-year-old Caucasian boy who presented with a two-year history of recurring acute parotitis with no fever. He had had a total of five episodes with no response to antibiotics, but remission had been achieved with oral corticosteroid therapy. We performed allergy tests for inhalant and food allergens and for haptens, but the results were all negative. The results of echography ruled out sialodochitis. Instead, a swab from the parotid duct led to the detection of a high number of eosinophils. Conclusions This report is first in the literature to describe a case of eosinophilic parotitis, and we suggest that a cytological assessment, which is quite simple yet rarely used by physicians, be performed when patients with parotitis of uncertain origin are under evaluation.

Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.

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Lu Huang

2015-12-01

Full Text Available It has become increasingly clear that the functions of eosinophils extend beyond host defense and allergy to metabolism and tissue regeneration. These influences have strong potential to be relevant in worm infections in which eosinophils are prominent and parasites rely on the host for nutrients to support growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that IL-4 and eosinophils are necessary for normal larval growth and that eosinophils from IL-4 competent mice are sufficient to support growth. The eosinophil-mediated effect operates in the absence of adaptive immunity. Following invasion by newborn larvae, host gene expression in skeletal muscle was compatible with a regenerative response and a shift in the source of energy in infected tissue. The presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4 and phosphorylation of Akt were observed in nurse cells, consistent with enhancement of glucose uptake and glycogen storage by larvae that is known to occur. The data are consistent with a mechanism in which eosinophils promote larval growth by an IL-4 dependent mechanism that limits local interferon-driven responses that otherwise alter nutrient metabolism in infected muscle. Our findings document a novel interaction between parasite and host in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth.

Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.

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Huang, Lu; Beiting, Daniel P; Gebreselassie, Nebiat G; Gagliardo, Lucille F; Ruyechan, Maura C; Lee, Nancy A; Lee, James J; Appleton, Judith A

2015-12-01

It has become increasingly clear that the functions of eosinophils extend beyond host defense and allergy to metabolism and tissue regeneration. These influences have strong potential to be relevant in worm infections in which eosinophils are prominent and parasites rely on the host for nutrients to support growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that IL-4 and eosinophils are necessary for normal larval growth and that eosinophils from IL-4 competent mice are sufficient to support growth. The eosinophil-mediated effect operates in the absence of adaptive immunity. Following invasion by newborn larvae, host gene expression in skeletal muscle was compatible with a regenerative response and a shift in the source of energy in infected tissue. The presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4) and phosphorylation of Akt were observed in nurse cells, consistent with enhancement of glucose uptake and glycogen storage by larvae that is known to occur. The data are consistent with a mechanism in which eosinophils promote larval growth by an IL-4 dependent mechanism that limits local interferon-driven responses that otherwise alter nutrient metabolism in infected muscle. Our findings document a novel interaction between parasite and host in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth.

Hematemesis as Initial Presentation in a 10-Week-Old Infant with Eosinophilic Gastroenteritis

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Varun Shetty

2017-01-01

Full Text Available Eosinophilic gastroenteritis is a rare condition characterized by eosinophilic inflammation in the gastrointestinal tract resulting in a variety of gastrointestinal symptoms. There is currently a dearth of information on this topic in the pediatric literature, as very few cases have been reported. In this report, we present a case of eosinophilic gastroenteritis in a 10-week-old patient with initial presenting symptom of hematemesis. To our knowledge, this is the youngest case reported in the literature and is unique in its initial presentation.

SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice.

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Percopo, Caroline M; Brenner, Todd A; Ma, Michelle; Kraemer, Laura S; Hakeem, Reem M A; Lee, James J; Rosenberg, Helene F

2017-01-01

Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45 + CD11c - SiglecF + Gr1 hi ). SiglecF + Gr1 hi eosinophils, distinct from the canonical SiglecF + Gr1 - eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX -/- and MBP-1 -/- ) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1 + neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF + Gr1 hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G + Although indistinguishable from the more-numerous SiglecF + Gr1 - eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF + Gr1 hi eosinophil population (at 3.9 and 4.8 pg/10 6 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/10 6 cells). Interestingly, bone marrow-derived (SiglecF + ), cultured eosinophils include a more substantial Gr1 + subpopulation (∼50%); Gr1 + bmEos includes primarily a single Ly6C + and a smaller, double-positive (Ly6C + Ly6G + ) population. Taken together, our findings characterize a distinct SiglecF + Gr1 hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF + Gr1 hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. © Society for Leukocyte Biology.

A Case Report of Eosinophilic Esophagitis Accompanying Hypereosinophilic Syndrome

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Mahreema Jawairia

2012-01-01

Full Text Available Hypereosinophilic syndrome is a blood disorder characterized by the overproduction of eosinophils in the bone marrow with persistent peripheral eosinophilia, associated with organ damage by the release of eosinophilic mediators. Although HES can involve multiple organ systems, GI tract involvement is very rare. Few cases of HES presenting with gastritis or enteritis have been reported worldwide. To date, HES presenting with esophagus involvement has only been reported once. Here, we present a 39-year-old Hispanic female patient with history of HES presenting with complaints of dysphagia and generalized pruritus.

Elevated Systemic Levels of Eosinophil, Neutrophil, and Mast Cell Granular Proteins in Strongyloides Stercoralis Infection that Diminish following Treatment.

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Rajamanickam, Anuradha; Munisankar, Saravanan; Bhootra, Yukthi; Dolla, Chandra Kumar; Nutman, Thomas B; Babu, Subash

2018-01-01

Infection with the helminth parasite Strongyloides stercoralis ( Ss ) is commonly clinically asymptomatic that is often accompanied by peripheral eosinophilia. Granulocytes are activated during helminth infection and can act as immune effector cells. Plasma levels of eosinophil and neutrophil granular proteins convey an indirect measure of granulocyte degranulation and are prominently augmented in numerous helminth-infected patients. In this study, we sought to examine the levels of eosinophil, neutrophil, and mast cell activation-associated granule proteins in asymptomatic Ss infection and to understand their kinetics following anthelmintic therapy. To this end, we measured the plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, neutrophil elastase, myeloperoxidase, neutrophil proteinase-3, mast cell tryptase, leukotriene C4, and mast cell carboxypeptidase-A3 in individuals with asymptomatic Ss infection or without Ss infection [uninfected (UN)]. We also estimated the levels of all of these analytes in infected individuals following definitive treatment of Ss infection. We demonstrated that those infected individuals have significantly enhanced plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, elastase, myeloperoxidase, mast cell tryptase, leukotriene C4, and carboxypeptidase-A3 compared to UN individuals. Following the treatment of Ss infection, each of these granulocyte-associated proteins drops significantly. Our data suggest that eosinophil, neutrophil, and mast cell activation may play a role in the response to Ss infection.

Eosinophilic spleen colonies are produced in rat-marrow-transplanted but not in murine-marrow-transplanted mice

International Nuclear Information System (INIS)

Szabo, L.G.; Kelemen, E.

1988-01-01

Differential counts of about 5000 splenic clusters and colonies developing in whole-body-irradiated mice and rats were made, using semi-serial histological sections prepared 9 to 12 d after transplantation with bone marrow haemopoietic cells. The investigated mouse and rat spleens were from syngeneically, allogeneically, or xenogeneically transplanted recipients. Splenic eosinophil clusters were always found when rat eosinophil-producing progenitors were present in the inoculum, whereas murine inocula failed to produce splenic eosinophilic clusters even in the syngeneic mouse. The limiting factor in the production pf splenic eosinophilic clusters was the appropriate donor progenitor/committed stem cell itself. Changes in the percentages of eosinophil clusters with the number of injected cells and with increased doses of irradiation, as well as formation of rat eosinophil colonies in mice, as against mainly clusters in rats, themselves show that regulatory mechanisms of the recipients also play a role. These regulatory mechanisms cannot be attributed to the splenic microenvironment. (author)

Eosinophil inversely associates with type 2 diabetes and insulin resistance in Chinese adults.

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Liying Zhu

Full Text Available CONTEXT: Limited population-based study focused on relationship between eosinophil and type 2 diabetes (T2D. OBJECTIVES: We aimed to evaluate the relationship between peripheral eosinophil percentage and glucose metabolism and insulin resistance in a large sample size of Chinese population aged 40 and older. DESIGN AND METHODS: A cross-sectional study was performed among 9,111 Chinese adults including 3,561 men and 5,550 women. The glucose metabolism status was confirmed by 75-g oral glucose tolerance test. Homeostasis model assessment of insulin resistance index and serum insulin levels were used to evaluate insulin resistance. Homeostasis model assessment-B was used to evaluate β cell function. RESULTS: The average age of participants was 58.5 years. The prevalence of T2D decreased across the tertiles of eosinophil percentage (21.3%, 18.2% and 16.9%, P<0.0001. Each one tertile increase of eosinophil percentage inversely associated with risk of T2D when referred not only to normal glucose tolerance (NGT (odds ratio (OR 0.81, 95% CI 0.76-0.87, P< 0.0001, but also to impaired glucose regulation (OR 0.89, 95% CI 0.83-0.97, P = 0.006, respectively, after adjustment for the confounding factors. Compared with the first tertile, the third tertile of eosinophil percentage associated with a 23% decrease of insulin resistance in NGT participants after full adjustments (P = 0.005. Each 1-standard deviation of increment of eosinophil percentage associated with a 37% decrease of insulin resistance (P = 0.005. CONCLUSIONS: Higher peripheral eosinophil percentage was associated with decreased risk of T2D. The inverse relation to insulin resistance was detected in NGT participants.

IL-5 Induces Suspended Eosinophils to Undergo Unique Global Reorganization Associated with Priming

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Han, Shih-Tsung

2014-01-01

The experiments described herein define a unique program of polarization of suspended human eosinophils stimulated with IL-5 family cytokines. We found that eosinophil granules and the nucleus move in opposite directions to form, respectively, a granular compartment and the nucleopod, a specialized uropod occupied by the nucleus and covered with adhesion receptors, including P-selectin glycoprotein ligand-1, CD44, and activated αMβ2 integrin. Ligated IL-5 family receptors localize specifically at the tip of the nucleopod in proximity to downstream signaling partners Janus tyrosine kinase 2, signal transducer and activator of transcription-1 and -5, and extracellular signal–regulated kinase. Microscopy and effects of cytochalasin B and nocodazole indicate that remodeling of filamentous actin and reorientation of the microtubule network are required for eosinophil polarization and nucleopod formation. IL-5 induces persistent polarization and extracellular signal–regulated kinase redistribution that are associated with eosinophil priming, a robust response on subsequent stimulation with N-formyl-methionyl-leucyl-phenylalanine. Global reorganization of cytoskeleton, organelles, adhesion receptors, and signaling molecules likely facilitates vascular arrest, extravasation, migration, granule release, and survival of eosinophils entering inflamed tissues from the bloodstream. PMID:24156300

Role of the eosinophil in serum-mediated adherence of equine leukocytes to infective larvae of Strongylus vulgaris.

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Klei, T R; Chapman, M R; Dennis, V A

1992-06-01

The adherence of equine leukocytes to Strongylus vulgaris infective larvae (L3) in the presence of normal and immune sera was examined in vitro. Immune sera promoted adherence of buffy coat cells from ponies with S. vulgaris-induced eosinophilia (eosinophilic ponies) to S. vulgaris L3. However, eosinophils in the buffy coat cells were the predominant adherent cell type. Studies using leukocyte populations enriched for eosinophils, neutrophils, and mononuclear cells from eosinophilic ponies support the observations using buffy coat cells that eosinophils were the main effector cells. Adherent eosinophils from eosinophilic ponies immobilized L3. Neutrophils were less adherent and did not immobilize L3. Mononuclear cells failed to adhere. Normal eosinophils from strongly-naive ponies did not immobilize S. vulgaris L3 in the presence of immune serum, suggesting the in vivo activation of eosinophils in eosinophilic animals. Immune serum promoted less adherence of buffy coat cells to Strongylus edentatus or mixed species of Cyathostominae L3, suggesting that the serum-mediated cellular adherence phenomenon was species-specific. Normal serum promoted less cellular adherence to S. vulgaris L3 than immune serum. The adherence mediated by normal serum was removed by heat inactivation, suggesting that this nonspecific phenomenon was a complement-mediated reaction. Immune globulins promoted reactions similar to that seen using heat-inactivated immune serum, whereas normal globulins did not promote adherence. Immune globulins absorbed with pieces of S. vulgaris adult worms did not promote the adherence of buffy coat cells to S. vulgaris L3, suggesting that adult and L3 stages share antigens important in this phenomenon that resulted in the removal of specific adherence antibody during absorption.

Eosinophilic Gastroenteritis as a Rare Cause of Recurrent Epigastric Pain

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Mohammad Taghi Safari

2016-04-01

Full Text Available 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.

Fibronectin changes in eosinophilic meningitis with blood-CSF barrier disruption.

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Shyu, Ling-Yuh; Hu, Ming-E; Chou, Chun-Hui; Chen, Ke-Min; Chiu, Ping-Sung; Lai, Shih-Chan

2015-01-01

Fibronectin, which is present at relatively low levels in healthy central nervous systems (CNS), shows increased levels in meningitis. In this study, fibronectin processing was correlated with the increased permeability of the blood-cerebrospinal fluid (CSF) barrier as well as with the formation of eosinophil infiltrates in angiostrongyliasis meningitis. The immunohistochemistry results show matrix metalloproteinase-9 (MMP-9) is localized in the choroid plexus epithelium. Coimmunoprecipitation demonstrated fibronectin strongly binds MMP-9. Furthermore, treatment with the MMP-9 inhibitor GM6001 significantly inhibited fibronectin processing, reduced the blood-CSF barrier permeability, and decreased the eosinophil counts. The decreased fibronectin processing in CSF implies decreased cellular invasion of the subarachnoid space across the blood-CSF barrier. Therefore, increased fibronectin processing may be associated with barrier disruption and participate in the extravasation and migration of eosinophils into the CNS during experimental parasitic infection. Copyright © 2015 Elsevier Inc. All rights reserved.

Combination of CD157 and FLAER to Detect Peripheral Blood Eosinophils by Multiparameter Flow Cytometry.

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Carulli, Giovanni; Marini, Alessandra; Sammuri, Paola; Domenichini, Cristiana; Ottaviano, Virginia; Pacini, Simone; Petrini, Mario

2015-01-01

The identification of eosinophils by flow cytometry is difficult because most of the surface antigens expressed by eosinophils are shared with neutrophils. Some methods have been proposed, generally based on differential light scatter properties, enhanced autofluorescence, lack of CD16 or selective positivity of CD52. Such methods, however, show several limitations. In the present study we report a novel method based on the analysis of glycosylphosphatidylinositol (GPI)-linked molecules. The combination of CD157 and FLAER was used, since FLAER recognizes all GPI-linked molecules, while CD157 is absent on the membrane of eosinophils and expressed by neutrophils. Peripheral blood samples from normal subjects and patients with variable percentages of eosinophils (n = 31), and without any evidence for circulating immature myeloid cells, were stained with the combination of FLAER-Alexa Fluor and CD157-PE. A FascCanto II cytometer was used. Granulocytes were gated after CD33 staining and eosinophils were identified as CD157(-)/FLAER(+) events. Neutrophils were identified as CD157(+)/FLAER(+) events. The percentages of eosinophils detected by this method showed a very significant correlation both with automated counting and with manual counting (r = 0.981 and 0.989, respectively). Sorting assays were carried out by a S3 Cell Sorter: cytospins obtained from CD157(-)/FLAER(+) events consisted of 100% eosinophils, while samples from CD157(+)/FLAER(+) events were represented only by neutrophils. In conclusion, this method shows high sensitivity and specificity in order to distinguish eosinophils from neutrophils by flow cytometry. However, since CD157 is gradually up-regulated throughout bone marrow myeloid maturation, our method cannot be applied to cases characterized by immature myeloid cells.

Eosinophilic Esophagitis in Brazilian Pediatric Patients

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Mayra Isabel Correia Pinheiro

2013-01-01

Full Text Available We examined 11 pediatric patients with eosinophilic esophagitis with a tardy diagnosis. The symptoms were initially thought to be related to other diseases, leading to the use of inadequate therapeutic approaches. The patients were between 3 and 17 years old (mean 7.8 ± 3.8 years, and 8 of the patients were male. Common symptoms included abdominal pain, regurgitation, difficulty in gaining weight, vomiting, dysphagia, and coughing. The mean age for the onset of symptoms was 4.3 ± 2.9 years. Endoscopic findings included normal mucosa in five (45% patients, thickening of the mucosa with longitudinal grooves in three (27%, erosive esophagitis in two (18%, and a whitish stippling in one (9% patient. Treatment included the use of a topical corticosteroid for 10 patients. In eight (73% cases, the treatment made the symptoms disappear. Ten patients underwent histopathological management after treatment, with a decrease in the number of eosinophils.

Bone marrow contribution to eosinophilic inflammation

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Denburg Judah A

1997-01-01

Full Text Available Allergen-induced bone marrow responses are observable in human allergic asthmatics, involving specific increases in eosinophil-basophil progenitors (Eo/B-CFU, measured either by hemopoietic assays or by flow cytometric analyses of CD34-positive, IL-3Ralpha-positive, and/or IL-5-responsive cell populations. The results are consistent with the upregulation of an IL-5-sensitive population of progenitors in allergen-induced late phase asthmatic responses. Studies in vitro on the phenotype of developing eosinophils and basophils suggest that the early acquisition of IL-5Ralpha, as well as the capacity to produce cytokines such as GM-CSF and IL-5, are features of the differentiation process. These observations are consistent with findings in animal models, indicating that allergen-induced increases in bone marrow progenitor formation depend on hemopoietic factor(s released post-allergen. The possibility that there is constitutive marrow upregulation of eosinophilopoiesis in allergic airways disease is also an area for future investigation.

Cutaneous mastocytomas in the neotenic caudate amphibians Ambystoma mexicanum (axolotl) and Ambystoma tigrinun (tiger salamander)

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Harshbarger, J.C.; Chang, S.C.; DeLanney, L.E.; Rose, F.L.; Green, D.E.

1999-01-01

Spontaneous mastocytomas studied in 18 axolotls (Ambystoma mexicanum) and six tiger salamanders (Ambystoma tigrinum) were gray-white, uni- to multilobular cutaneous protrusions from 2mm to 2cm in diameter. Tumors were moderately cellular unencapsulated masses that usually infiltrated the dermis and hypodermis with the destruction of intervening tissues. Some tumors were invading superficial bundles of the underlying skeletal muscle. Tumors consisted of mitotically active cells derived from a single lineage but showing a range of differentiation. Immature cells had nearly smooth to lightly cleft or folded basophilic nuclei bordered by a band of cytoplasm with few cytoplasmic processes and containing a few small uniform eccentric granules. Mature cells had basophilic nuclei with deep clefts or folds and abundant eosinophilic cytoplasm with multiple long intertwining cytoplasmic extensions packed with metachromatic granules. The axolotls were old individuals from an inbred laboratory colony. The tiger salamanders were wild animals from a single polluted pond. They could have been old and inbred. Both groups were neotenic. These are the first mastocytomas discovered in cold-blooded animals.

Cytoplasmic Z-RNA

International Nuclear Information System (INIS)

Zarling, D.A.; Calhoun, C.J.; Hardin, C.C.; Zarling, A.H.

1987-01-01

Specific immunochemical probes for Z-RNA were generated and characterized to search for possible Z-RNA-like double helices in cells. Z-RNA was detected in the cytoplasm of fixed protozoan cells by immunofluorescence microscopy using these anti-Z-RNA IgCs. In contrast, autoimmune or experimentally elicited anti-DNA antibodies, specifically reactive with B-DNA or Z-DNA, stained the nuclei. Pre-or nonimmune IgGs did not bind to the cells. RNase A or T1 digestion eliminated anti-Z-RNA IgG binding to cytoplasmic determinants; however, DNase I or mung bean nuclease had no effect. Doxorubicin and ethidium bromide prevented anti-Z-RNA antibody binding; however, actinomycin D, which does not bind double-stranded RNA, did not. Anti-Z-RNA immunofluorescence was specifically blocked in competition assays by synthetic Z-RNA but not Z-DNA, A-RNA, or single-stranded RNAs. Thus, some cytoplasmic sequences in fixed cells exist in the left-handed Z-RNA conformation

Allergen-Induced Increases in Interleukin-25 and Interleukin-25 Receptor Expression in Mature Eosinophils from Atopic Asthmatics.

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Tang, Wei; Smith, Steven G; Salter, Brittany; Oliveria, John Paul; Mitchell, Patrick; Nusca, Graeme M; Howie, Karen; Gauvreau, Gail M; O'Byrne, Paul M; Sehmi, Roma

2016-01-01

Interleukin (IL)-25 plays a pivotal role in type 2 immune responses. In a baseline cross-sectional study, we previously showed that IL-25 plasma levels and IL-25 receptor (IL-25R: IL-17RA, IL-17RB, and IL-17RA/RB) expression on mature blood eosinophils are increased in atopic asthmatics compared to normal nonatopic controls. This study investigated allergen-induced changes in IL-25 and IL-25R expression in eosinophils from asthmatics. Dual responder atopic asthmatics (n = 14) were enrolled in this randomized diluent-controlled crossover allergen challenge study. Blood was collected before and 24 h after the challenge. The surface expression of IL-25R was evaluated by flow cytometry on eosinophils and Th2 memory cells. In addition, plasma levels of IL-25 were measured by ELISA, and functional responses to IL-25 including type 2 cytokine expression, degranulation, and the migrational responsiveness of eosinophils were evaluated in vitro. Following the allergen but not the diluent inhalation challenge, significant increases in the expression of IL-17RB and IL-17RA/B were found on eosinophils but not on Th2 memory cells. IL-25 plasma levels and the number of eosinophils but not of Th2 memory cells expressing intracellular IL-25 increased significantly in response to the allergen but not the diluent challenge. Stimulation with physiologically relevant concentrations of IL-25 in vitro caused (i) degranulation of eosinophils (measured by eosinophil peroxidase release), (ii) enhanced intracellular expression of IL-5 and IL-13, and (iii) priming of eosinophil migration to eotaxin. IL-25 stimulated intracellular cytokine expression, and the migration of eosinophils was blocked in the presence of a neutralizing IL-25 antibody. Our findings suggest that the IL-25/IL-25R axis may play an important role in promoting the recruitment and proinflammatory function of eosinophils in allergic asthma. © 2016 S. Karger AG, Basel.

Antibody-secreting cells in respiratory tract tissues in the absence of eosinophils as supportive partners.

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Sealy, Robert E; Surman, Sherri L; Vogel, Peter; Hurwitz, Julia L

2016-11-01

Antibody-secreting cells (ASCs) in respiratory tract tissues provide a first line of defense against invading pathogens. These cells often secrete IgA that is efficiently transcytosed across epithelial barriers into the airway lumen where pathogens can be blocked at their point of entry. Previous literature has reported that in the bone marrow, eosinophils are required for the maintenance of ASCs, and that eosinophils co-localize with ASCs as nearest neighbors. To determine if these rules similarly apply to the maintenance of ASCs in respiratory tract tissues, we evaluated virus-specific responses 1 month and 4 months following an intranasal virus infection of eosinophil-null (∆dblGATA-1) mice. Results showed that ASCs were fractionally reduced, but were nonetheless observed in respiratory tract tissues in the absence of eosinophils. Virus-specific antibodies were similarly observed in the airways of eosinophil-deficient mice. Respiratory tract ASCs were also present in mice lacking neutrophils (Mcl1 ∆M ). The staining of tissue sections from the upper respiratory tract of wild-type mice following viral infections demonstrated that virus-specific ASCs were most frequently situated adjacent to epithelial cells rather than eosinophils or neutrophils. Taken together, these data emphasize that rules for cell maintenance are not absolute and that ASCs can survive in the respiratory tract without eosinophils or neutrophils as their nearest neighbors. © The Japanese Society for Immunology. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Helminth antigens counteract a rapid high-fat diet-induced decrease in adipose tissue eosinophils.

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van den Berg, Susan M; van Dam, Andrea D; Kusters, Pascal J H; Beckers, Linda; den Toom, Myrthe; van der Velden, Saskia; Van den Bossche, Jan; van Die, Irma; Boon, Mariëtte R; Rensen, Patrick C N; Lutgens, Esther; de Winther, Menno P J

2017-10-01

Brown adipose tissue (BAT) activation and white adipose tissue (WAT) beiging can increase energy expenditure and have the potential to reduce obesity and associated diseases. The immune system is a potential target in mediating brown and beige adipocyte activation. Type 2 and anti-inflammatory immune cells contribute to metabolic homeostasis within lean WAT, with a prominent role for eosinophils and interleukin (IL)-4-induced anti-inflammatory macrophages. We determined eosinophil numbers in epididymal WAT (EpAT), subcutaneous WAT (ScAT) and BAT after 1 day, 3 days or 1 week of high-fat diet (HFD) feeding in C57Bl/6 mice. One day of HFD resulted in a rapid drop in eosinophil numbers in EpAT and BAT, and after 3 days, in ScAT. In an attempt to restore this HFD-induced drop in adipose tissue eosinophils, we treated 1-week HFD-fed mice with helminth antigens from Schistosoma mansoni or Trichuris suis and evaluated whether the well-known protective metabolic effects of helminth antigens involves BAT activation or beiging. Indeed, antigens of both helminth species induced high numbers of eosinophils in EpAT, but failed to induce beiging. In ScAT, Schistosoma mansoni antigens induced mild eosinophilia, which was accompanied by slightly more beiging. No effects were observed in BAT. To study type 2 responses on brown adipocytes directly, T37i cells were stimulated with IL-4. This increased Ucp1 expression and strongly induced the production of eosinophil chemoattractant CCL11 (+26-fold), revealing that brown adipocytes themselves can attract eosinophils. Our findings indicate that helminth antigen-induced eosinophilia fails to induce profound beiging of white adipocytes. © 2017 Society for Endocrinology.

Association of interleukin 1 receptor-like 1 gene polymorphisms with eosinophilic phenotype in Japanese adults with asthma.

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Inoue, Hideki; Ito, Isao; Niimi, Akio; Matsumoto, Hisako; Oguma, Tsuyoshi; Tajiri, Tomoko; Iwata, Toshiyuki; Nagasaki, Tadao; Kanemitsu, Yoshihiro; Morishima, Toshitaka; Hirota, Tomomitsu; Tamari, Mayumi; Wenzel, Sally E; Mishima, Michiaki

2017-11-01

IL1RL1 (ST2) is involved in Th2 inflammation including eosinophil activation. Single nucleotide polymorphisms (SNPs) of the IL1RL1 gene are associated with asthma development and increased peripheral blood eosinophil counts. However, the association between IL1RL1 SNPs and eosinophilic phenotype among adults with asthma remains unexplored. In a primary cohort of 110 adult Japanese patients with stable asthma, we examined the associations between IL1RL1 SNPs and clinical measurements including forced expiratory volume (FEV 1 ), airway reversibility of FEV 1 , exhaled nitric oxide (FeNO), serum soluble-ST2 (sST2) levels, peripheral blood eosinophil differentials and serum total IgE level. The findings in the primary cohort were confirmed in a validation cohort of 126 adult Japanese patients with stable asthma. Patients with minor alleles in 3 SNPs (rs17026974, rs1420101, and rs1921622) had high FeNO, blood eosinophil differentials, and reversibility of FEV 1 , but low levels of serum sST2 and FEV 1 . Minor alleles of rs1041973 were associated with low serum sST2 levels alone. In the validation cohort, minor alleles of rs1420101 were associated with high FeNO and blood eosinophil differentials, whereas minor alleles of rs17026974 and rs1921622 were associated with high blood eosinophil differentials and FeNO, respectively. Multivariate analyses revealed that the minor allele of rs1420101 additively contributed to the FeNO, blood eosinophil differentials, and reversibility of FEV 1 . The minor alleles of IL1RL1 SNPs were associated with high FeNO and peripheral blood eosinophilia among adult Japanese patients with stable asthma. IL1RL1 SNPs may characterize the eosinophilic phenotype with greater eosinophilic inflammation in the Japanese asthma cohort. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

The Pathophysiology of Eosinophilic Esophagitis

Directory of Open Access Journals (Sweden)

Daniel Avi Lemberg

2014-05-01

Full Text Available Eosinophilic Esophagitis (EoE is an emerging disease characterised 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 TGF-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.

The distribution of blood eosinophil levels in a Japanese COPD clinical trial database and in the rest of the world

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Ishii, Takeo; Hizawa, Nobuyuki; Midwinter, Dawn; James, Mark; Hilton, Emma; Jones, Paul W

2018-01-01

Background Blood eosinophil measurements may help to guide physicians on the use of inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD). Emerging data suggest that COPD patients with higher blood eosinophil counts may be at higher risk of exacerbations and more likely to benefit from combined ICS/long-acting beta2-agonist (LABA) treatment than therapy with a LABA alone. This analysis describes the distribution of blood eosinophil count at baseline in Japanese COPD patients in comparison with non-Japanese COPD patients. Methods A post hoc analysis of eosinophil distribution by percentage and absolute cell count was performed across 12 Phase II–IV COPD clinical studies (seven Japanese studies [N=848 available absolute eosinophil counts] and five global studies [N=5,397 available eosinophil counts] that included 246 Japanese patients resident in Japan with available counts). Blood eosinophil distributions were assessed at baseline, before blinded treatment assignment. Findings Among Japanese patients, the median (interquartile range) absolute eosinophil count was 170 cells/mm3 (100–280 cells/mm3). Overall, 612/1,094 Japanese patients (56%) had an absolute eosinophil count ≥150 cells/mm3 and 902/1,304 Japanese patients (69%) had a percentage eosinophil ≥2%. Among non-Japanese patients, these values were 160 (100–250) cells/mm3, 2,842/5,151 patients (55%), and 2,937/5,155 patients (57%), respectively. The eosinophil distribution among Japanese patients was similar to that among non-Japanese patients. Within multi-country studies with similar inclusion criteria, the eosinophil count was numerically lower in Japanese compared with non-Japanese patients (median 120 vs 160 cells/mm3). Interpretation The eosinophil distribution in Japanese patients seems comparable to that of non-Japanese patients; although within multi-country studies, there was a slightly lower median eosinophil count for Japanese patients compared with

Airway eosinophils accumulate in the mediastinal lymph nodes but lack antigen-presenting potential for naive T cells

NARCIS (Netherlands)

van Rijt, Leonie S.; Vos, Nanda; Hijdra, Daniëlle; de Vries, Victor C.; Hoogsteden, Henk C.; Lambrecht, Bart N.

2003-01-01

Asthma is characterized by infiltration of the airway wall with eosinophils. Although eosinophils are considered to be effector cells, recent studies have reported their ability to activate primed Th2 cells. In this study, we investigated whether eosinophils are capable of presenting Ag to unprimed

Human eosinophils modulate peripheral blood mononuclear cell response to Schistosoma mansoni adult worm antigen in vitro.

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Tweyongyere, R; Namanya, H; Naniima, P; Cose, S; Tukahebwa, E M; Elliott, A M; Dunne, D W; Wilson, S

2016-08-01

High numbers of eosinophils are observed in parasitic infections and allergic diseases, where they are proposed to be terminally differentiated effector cells that play beneficial role in host defence, or cause harmful inflammatory response. Eosinophils have been associated with killing of schistosomulae in vitro, but there is growing evidence that eosinophils can play additional immuno-regulatory role. Here, we report results of a study that examines peripheral blood mononuclear cell (PBMC) cytokine responses to Schistosoma mansoni adult worm antigen (SWA) when stimulated alone or enriched with autologous eosinophils. Production of the Th-2 type cytokines interleukin (IL)-4, IL-5 and IL-13 was lower (P = 0·017, 0·018 and eosinophil cultures than in PBMC-only cultures stimulated with SWA. Substantial levels of IL-13, IL-10, interferon gamma and tumour necrosis factor alpha were recorded in cultures of eosinophils, but none of these cytokines showed significant association with the observed eosinophil-induced drop in cytokine responses of PBMC. Transwell experiments suggested that the observed effect is due to soluble mediators that downmodulate production of Th-2 type cytokines. This study shows that eosinophils may down-modulate schistosome-specific Th-2 type cytokine responses in S. mansoni-infected individuals. The mechanism of this immune modulation remains to be elucidated. © 2016 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

Urinary Eosinophil Protein X in Childhood Asthma : Relation with Changes in Disease Control and Eosinophilic Airway Inflammation

NARCIS (Netherlands)

Nuijsink, Marianne; Hop, Wim C. J.; Sterk, Peter J.; Duiverman, Eric J.; De Jongste, Johan C.

2013-01-01

The aim of this study was to assess cross-sectional and longitudinal correlations between uEPX and other markers of asthma control and eosinophilic airway inflammation. Methods. We measured uEPX at baseline, after 1 year and after 2 years in 205 atopic asthmatic children using inhaled fluticasone.

Pyloric obstruction due to massive eosinophilic infiltration in a young adult dog.

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Konstantinidis, Alexandros O; Mylonakis, Mathios E; Psalla, Dimitra; Soubasis, Nectarios; Papadimitriou, Dimitrios; Rallis, Timoleon S

2017-11-01

A 16-month-old dog was presented with chronic vomiting, anorexia, progressive weight loss, and melena. Exploratory laparotomy revealed a massive pyloric eosinophilic infiltration leading to pyloric obstruction that was treated successfully with pylorectomy. This is a novel clinical presentation of eosinophilic gastritis and highlights the need to consider it as a differential diagnosis for pyloric obstruction.

[Non allergic simple eosinophilic pneumonia--Löffler syndrome--a case report study].

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Meta-Jevtović, Ivana; Tomović, Miroslav S; Mojsilović, Slavica; Petrović, Marina

2008-01-01

Löffler syndrome is an acute, pneumonia of unknown ethiology. This disease is not often associated with bronchial asthma. In its asymptomatic form, this disease is reversible, transient, self-limited with no requests for specific therapy regimen. In the symptomatic form, as well as during its progression, treatment with steroids is very effective. Furthermore, in both acute eosinophilic and idiopathic chronic eosinophilic form, this kind of therapy ensures survival. The case of a 53-year-old Caucasian woman was presented with 2-month history of low grade fever, shortness of breath, cough and reduced exercise tolerance. Although she had an allergic accident on insects in history, non allergy reactions as well as an obstructive disease with that kind of origin were not detected on admission. The diagnosis of simple eosinophilic pneumonia (SEP) (Löffler's syndrome) was confirmed by transbronchial biopsy and by sternal testing. The peripheral blood eosinophilia with pulmonary eosinophilic infiltrates on X ray chest radiography were observed during clinical examination. Biopsy specimen of the lung parenchym showed changes associated with Löffler's syndrome. The diagnosis was, also, confirmed according to the radiographic findings of unilateral migratory infiltrates consistent pneumonia. Churg Strauss syndrome (CSS) has to be considered in this differential diagnosis. Frequently, this disease has extrinsic bronchial asthma with eosinophilic pneumonia in history: asthma is often associated with allergic bronchopulmonary aspergillosis. In the reported case, treatment with steroids resulted in a marked clinical improvement compared to nonsteroid therapy.

A possible mechanism in the recruitment of eosinophils and Th2 cells through CD163(+) M2 macrophages in the lesional skin of eosinophilic cellulitis.

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Fujimura, Taku; Kambayashi, Yumi; Furudate, Sadanori; Kakizaki, Aya; Aiba, Setsuya

2014-01-01

M2 macrophages play a critical role in the recruitment of T helper 2 (Th2) regulatory T cells (Treg). To study the role of M2 macrophages and Treg cells in eosinophilic celulitis. We employed immunohistochemical staining for CD163( )and CD206 (macrophages) as well as FoxP3 (Treg), in lesional skin of four cases of eosinophilic cellulitis. CD163(+) CD206(+) M2 macrophages, which were previously reported to produce CCL17 to induce Th2 cells and Treg cells, were predominantly infiltrating the subcutaneous tissues and interstitial area of the dermis. M2 macrophages derived from PBMC showed significantly increased expression of CCL11, CCL17, CCL24 and CCL26 mRNA and production of CCL17 and CCL24, when stimulated by IL-4 or IL- 13. In addition, CCL17-producing cells and CCL24-producing cells were prominent in the lesional skin of EC. Our study sheds light on one of the possible immunological mechanisms of eosinophilic cellulitis.

Eosinophils may play regionally disparate roles in influencing IgA(+) plasma cell numbers during large and small intestinal inflammation.

Science.gov (United States)

Forman, Ruth; Bramhall, Michael; Logunova, Larisa; Svensson-Frej, Marcus; Cruickshank, Sheena M; Else, Kathryn J

2016-05-31

Eosinophils are innate immune cells present in the intestine during steady state conditions. An intestinal eosinophilia is a hallmark of many infections and an accumulation of eosinophils is also observed in the intestine during inflammatory disorders. Classically the function of eosinophils has been associated with tissue destruction, due to the release of cytotoxic granule contents. However, recent evidence has demonstrated that the eosinophil plays a more diverse role in the immune system than previously acknowledged, including shaping adaptive immune responses and providing plasma cell survival factors during the steady state. Importantly, it is known that there are regional differences in the underlying immunology of the small and large intestine, but whether there are differences in context of the intestinal eosinophil in the steady state or inflammation is not known. Our data demonstrates that there are fewer IgA(+) plasma cells in the small intestine of eosinophil-deficient ΔdblGATA-1 mice compared to eosinophil-sufficient wild-type mice, with the difference becoming significant post-infection with Toxoplasma gondii. Remarkably, and in complete contrast, the absence of eosinophils in the inflamed large intestine does not impact on IgA(+) cell numbers during steady state, and is associated with a significant increase in IgA(+) cells post-infection with Trichuris muris compared to wild-type mice. Thus, the intestinal eosinophil appears to be less important in sustaining the IgA(+) cell pool in the large intestine compared to the small intestine, and in fact, our data suggests eosinophils play an inhibitory role. The dichotomy in the influence of the eosinophil over small and large intestinal IgA(+) cells did not depend on differences in plasma cell growth factors, recruitment potential or proliferation within the different regions of the gastrointestinal tract (GIT). We demonstrate for the first time that there are regional differences in the requirement of

Eosinophil granule proteins ECP and EPX as markers for a potential early-stage inflammatory lesion in female genital schistosomiasis (FGS)

DEFF Research Database (Denmark)

Ramarokoto, Charles Emile; Kildemoes, Anna M. O.; Randrianasolo, Bodo Sahondra

2014-01-01

pathology, as viable schistosome egg granulomas often are eosinophil rich. Here it was investigated whether eosinophil granule proteins ECP (eosinophil cationic protein) and EPX (eosinophil protein-X) in urine and genital lavage can be used as markers for active FGS lesions. METHODS: Uro-genital samples...

Endogenous secreted phospholipase A2 group X regulates cysteinyl leukotrienes synthesis by human eosinophils.

Science.gov (United States)

Hallstrand, Teal S; Lai, Ying; Hooper, Kathryn A; Oslund, Rob C; Altemeier, William A; Matute-Bello, Gustavo; Gelb, Michael H

2016-01-01

Phospholipase A2s mediate the rate-limiting step in the formation of eicosanoids such as cysteinyl leukotrienes (CysLTs). Group IVA cytosolic PLA2α (cPLA2α) is thought to be the dominant PLA2 in eosinophils; however, eosinophils also have secreted PLA2 (sPLA2) activity that has not been fully defined. To examine the expression of sPLA2 group X (sPLA2-X) in eosinophils, the participation of sPLA2-X in the formation of CysLTs, and the mechanism by which sPLA2-X initiates the synthesis of CysLTs in eosinophils. Peripheral blood eosinophils were obtained from volunteers with asthma and/or allergy. A rabbit polyclonal anti-sPLA2-X antibody identified sPLA2-X by Western blot. We used confocal microscopy to colocalize the sPLA2-X to intracellular structures. An inhibitor of sPLA2-X (ROC-0929) that does not inhibit other mammalian sPLA2s, as well as inhibitors of the mitogen-activated kinase cascade (MAPK) and cPLA2α, was used to examine the mechanism of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-mediated formation of CysLT. Eosinophils express the mammalian sPLA2-X gene (PLA2G10). The sPLA2-X protein is located in the endoplasmic reticulum, golgi, and granules of eosinophils and moves to the granules and lipid bodies during fMLP-mediated activation. Selective sPLA2-X inhibition attenuated the fMLP-mediated release of arachidonic acid and CysLT formation by eosinophils. Inhibitors of p38, extracellular-signal-regulated kinases 1/2 (p44/42 MAPK), c-Jun N-terminal kinase, and cPLA2α also attenuated the fMLP-mediated formation of CysLT. The sPLA2-X inhibitor reduced the phosphorylation of p38 and extracellular-signal-regulated kinases 1/2 (p44/42 MAPK) as well as cPLA2α during cellular activation, indicating that sPLA2-X is involved in activating the MAPK cascade leading to the formation of CysLT via cPLA2α. We further demonstrate that sPLA2-X is activated before secretion from the cell during activation. Short-term priming with IL-13 and TNF/IL-1β increased the

Urinary eosinophil protein X in childhood asthma: relation with changes in disease control and eosinophilic airway inflammation

NARCIS (Netherlands)

Nuijsink, Marianne; Hop, Wim C. J.; Sterk, Peter J.; Duiverman, Eric J.; de Jongste, Johan C.

2013-01-01

The aim of this study was to assess cross-sectional and longitudinal correlations between uEPX and other markers of asthma control and eosinophilic airway inflammation. Methods. We measured uEPX at baseline, after 1 year and after 2 years in 205 atopic asthmatic children using inhaled fluticasone.

Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort.

Science.gov (United States)

Hastie, Annette T; Martinez, Fernando J; Curtis, Jeffrey L; Doerschuk, Claire M; Hansel, Nadia N; Christenson, Stephanie; Putcha, Nirupama; Ortega, Victor E; Li, Xingnan; Barr, R Graham; Carretta, Elizabeth E; Couper, David J; Cooper, Christopher B; Hoffman, Eric A; Kanner, Richard E; Kleerup, Eric; O'Neal, Wanda K; Paine, Richard; Peters, Stephen P; Alexis, Neil E; Woodruff, Prescott G; Han, MeiLan K; Meyers, Deborah A; Bleecker, Eugene R

2017-12-01

Increased concentrations of eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with increased frequency of exacerbations, reduced lung function, and corticosteroid responsiveness. We aimed to assess whether high eosinophil concentrations in either sputum or blood are associated with a severe COPD phenotype, including greater exacerbation frequency, and whether blood eosinophils are predictive of sputum eosinophils. We did a multicentre observational study analysing comprehensive baseline data from SPIROMICS in patients with COPD aged 40-80 years who had a smoking history of at least 20 pack-years, recruited from six clinical sites and additional subsites in the USA between Nov 12, 2010, and April 21, 2015. Inclusion criteria for this analysis were SPIROMICS baseline visit data with complete blood cell counts and, in a subset, acceptable sputum counts. We stratified patients on the basis of blood and sputum eosinophil concentrations and compared their demographic characteristics, as well as results from questionnaires, clinical assessments, and quantitative CT (QCT). We also analysed whether blood eosinophil concentrations reliably predicted sputum eosinophil concentrations. This study is registered with ClinicalTrials.gov (NCT01969344). Of the 2737 patients recruited to SPIROMICS, 2499 patients were smokers and had available blood counts, and so were stratified by mean blood eosinophil count: 1262 patients with low (George Respiratory Questionnaire symptom scores (p=0·037), and increased wheezing (p=0·018), but no evidence of an association with COPD exacerbations (p=0·35) or the other indices of COPD severity, such as emphysema measured by CT density, COPD assessment test scores, Body-mass index, airflow Obstruction, Dyspnea, and Exercise index, or Global Initiative for Chronic Obstructive Lung Disease stage. Blood eosinophil counts showed a weak but significant association with sputum eosinophil counts

Reliability of histologic assessment in patients with eosinophilic oesophagitis.

Science.gov (United States)

Warners, M J; Ambarus, C A; Bredenoord, A J; Verheij, J; Lauwers, G Y; Walsh, J C; Katzka, D A; Nelson, S; van Viegen, T; Furuta, G T; Gupta, S K; Stitt, L; Zou, G; Parker, C E; Shackelton, L M; D Haens, G R; Sandborn, W J; Dellon, E S; Feagan, B G; Collins, M H; Jairath, V; Pai, R K

2018-04-01

The validity of the eosinophilic oesophagitis (EoE) histologic scoring system (EoEHSS) has been demonstrated, but only preliminary reliability data exist. Formally assess the reliability of the EoEHSS and additional histologic features. Four expert gastrointestinal pathologists independently reviewed slides from adult patients with EoE (N = 45) twice, in random order, using standardised training materials and scoring conventions for the EoEHSS and additional histologic features agreed upon during a modified Delphi process. Intra- and inter-rater reliability for scoring the EoEHSS, a visual analogue scale (VAS) of overall histopathologic disease severity, and additional histologic features were assessed using intra-class correlation coefficients (ICCs). Almost perfect intra-rater reliability was observed for the composite EoEHSS scores and the VAS. Inter-rater reliability was also almost perfect for the composite EoEHSS scores and substantial for the VAS. Of the EoEHSS items, eosinophilic inflammation was associated with the highest ICC estimates and consistent with almost perfect intra- and inter-rater reliability. With the exception of dyskeratotic epithelial cells and surface epithelial alteration, ICC estimates for the remaining EoEHSS items were above the benchmarks for substantial intra-rater, and moderate inter-rater reliability. Estimation of peak eosinophil count and number of lamina propria eosinophils were associated with the highest ICC estimates among the exploratory items. The composite EoEHSS and most component items are associated with substantial reliability when assessed by central pathologists. Future studies should assess responsiveness of the score to change after a therapeutic intervention to facilitate its use in clinical trials. © 2018 John Wiley & Sons Ltd.

Eosinophilic myositis as first manifestation in a patient with type 2 myotonic dystrophy CCTG expansion mutation and rheumatoid arthritis.

Science.gov (United States)

Meyer, Alain; Lannes, Béatrice; Carapito, Raphaël; Bahram, Seiamak; Echaniz-Laguna, Andoni; Geny, Bernard; Sibilia, Jean; Gottenberg, Jacques Eric

2015-02-01

Eosinophilic myositis is characterized by eosinophilic infiltration of skeletal muscles. In the absence of an identifiable causative factor or source (including parasitic infection, intake of drugs or L-tryptophan, certain systemic disorders as well as malignant diseases), the diagnosis of idiopathic eosinophilic myositis is usually retained. However, some muscular dystrophies have been recently identified in this subset of eosinophilic myositis. Here, we report a patient with an 8 kb CCTG expansion in intron 1 of the CNBP gene, a mutation characteristic of myotonic dystrophy type 2 (DM2), whose first manifestation was "idiopathic" eosinophilic myositis. This report suggests that in "idiopathic" eosinophilic myositis, clinicians should consider muscular dystrophies, including DM2. Copyright © 2014 Elsevier B.V. All rights reserved.

Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle

1999-01-01

-assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used...... age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies...... should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth....

Eosinophilic Meningitis Caused by Angiostrongylus cantonensis in an Adolescent With Mental Retardation and Pica Disorder

Directory of Open Access Journals (Sweden)

Chang-Wei Hsueh

2013-02-01

Full Text Available Eosinophilic meningitis or encephalitis is a rare disorder and is most commonly caused by Angiostrongylus cantonensis. Humans are accidentally infected when they ingest raw snails or vegetables contaminated with the parasite larvae. Because of the improvement in sanitary food handling practices, the occurrence of A. cantonensis eosinophilic meningitis has been decreasing in Taiwan in recent decades. The common symptoms and signs of eosinophilic meningitis are severe headache, neck stiffness, paresthesia, vomiting, nausea, and fever. Acute urinary retention is a rare presentation. We report a case of A. cantonensis eosinophilic meningitis in an intellectually disabled patient who presented with acute urinary retention without any other meningeal signs. The patient received supportive treatment with corticosteroid therapy and was discharged and received urinary rehabilitation at home.

An ultrastructural study of the interaction of human eosinophils with respiratory syncytial virus

NARCIS (Netherlands)

Kimpen, JLL; Garofalo, R; Welliver, RC; Fujihara, K; Ogra, PL

It was shown previously that eosinophils are activated in vivo and in vitro by respiratory syncytial virus (RSV) (Garofalo et al., J Pediatr 1992: 120: 28-32; Kimpen et al., Pediatr Res 1992: 32: 160-4). For study of the interaction of eosinophils and RSV on the ultrastructural level, normodense

Cellular Subcompartments through Cytoplasmic Streaming.

Science.gov (United States)

Pieuchot, Laurent; Lai, Julian; Loh, Rachel Ann; Leong, Fong Yew; Chiam, Keng-Hwee; Stajich, Jason; Jedd, Gregory

2015-08-24

Cytoplasmic streaming occurs in diverse cell types, where it generally serves a transport function. Here, we examine streaming in multicellular fungal hyphae and identify an additional function wherein regimented streaming forms distinct cytoplasmic subcompartments. In the hypha, cytoplasm flows directionally from cell to cell through septal pores. Using live-cell imaging and computer simulations, we identify a flow pattern that produces vortices (eddies) on the upstream side of the septum. Nuclei can be immobilized in these microfluidic eddies, where they form multinucleate aggregates and accumulate foci of the HDA-2 histone deacetylase-associated factor, SPA-19. Pores experiencing flow degenerate in the absence of SPA-19, suggesting that eddy-trapped nuclei function to reinforce the septum. Together, our data show that eddies comprise a subcellular niche favoring nuclear differentiation and that subcompartments can be self-organized as a consequence of regimented cytoplasmic streaming. Copyright © 2015 Elsevier Inc. All rights reserved.

Malignant mast cell tumor of the thymus in an Royal College of Surgeons (RCS) rat.

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Terayama, Yui; Matsuura, Tetsuro; Ozaki, Kiyokazu

2017-01-01

A 152-week-old male Royal College of Surgeons (RCS) rat kept as a non-treated animal in a long-term animal study presented with a soft mass in the anterior mediastinum, which adhered to the pleura of the lung. Histopathologically, the mass mainly consisted of round to short spindle-shaped tumor cells that had infiltrated through the hyperplastic thymic tissue. The tumor cells were arranged in loose to dense sheets. Nuclei were moderate in size and round to spindle-shaped, with small nucleoli. Almost all tumor cells exhibited abundant eosinophilic cytoplasm, including eosinophilic granules of a range of sizes. The granules of tumor cells exhibited metachromasia with toluidine blue stain and were positive for c-kit and mast cell protease II. These findings indicate that the tumor described here represents a rare case of spontaneous malignant mast cell tumor with thymic epithelial hyperplasia.

Elevated blood eosinophils in early infancy are predictive of atopic dermatitis in children with risk for atopy.

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Rossberg, Siri; Gerhold, Kerstin; Geske, Thomas; Zimmermann, Kurt; Menke, Georg; Zaino, Mohammad; Wahn, Ulrich; Hamelmann, Eckard; Lau, Susanne

2016-11-01

Accessible markers to predict the development of atopic diseases are highly desirable but yet matter of debate. We investigated the role of blood eosinophils at 4 weeks and 7 months of life and their association with developing atopic dermatitis (AD) in a birth cohort of children with atopic heredity. Infant blood samples for eosinophil counts were taken from 559 infants at 4 weeks and from 467 infants at 7 month of life with at least one atopic parent. Elevation of blood eosinophils was defined as ≥ 5% of total leukocytes and the asscociation for the occurrence of AD was assessed by entering 2 × 2 tables and the odds ratios were estimated followed by hypothesis testing against the alternate working hypothesis: odds ratio 1. Survival analysis was carried out estimating the Kaplan-Meier product limit estimator from the life-time table of AD score and time to AD manifestation stratified by the eosinophil binary score. Elevated blood eosinophils observed at 4 weeks were significantly associated with the occurrence of AD in the whole cohort at the age of 7 months (p = 0.007), 1 year (p = 0.004), 2 years (p = 0.007) and 3 years (p = 0.006) of life. AD occurred app. 12 weeks earlier in infants with elevated blood eosinophils at 4 weeks of life. Blood eosinophil counts ≥5% at 7 months of life failed to show significance for AD; for eosinophils at 4.5% a significant association at 7 months (p = 0.005), and 1 year of life (p = 0.039), 2 years (p = 0.033) and 3 years (p = 0.034) was observed. Elevated blood eosinophils at age 4 weeks have a predictive value for the onset of atopic dermatitis in infancy and early childhood in children with high risk for atopy. Early eosinophil counts may therefore be helpful for counseling parents to provide infant skincare but furthermore identify individuals for interventional trials aiming at allergy prevention. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eosinophilic airway inflammation is increased in children with asthma and food allergies.

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Kulkarni, Neeta; Ragazzo, Vincenzo; Costella, Silvia; Piacentini, Giorgio; Boner, Attilio; O'Callaghan, Christopher; Fiocchi, Alessandro; Kantar, Ahmad

2012-02-01

Asthma is associated with food allergies in a significant number of children, with evidence linking allergies to asthma severity and morbidity. In this study, we tested our hypothesis that the eosinophilic lower airway inflammation is higher in asthmatic children with food allergies. The aims of the study were to compare the eosinophilic inflammatory markers in asthmatic children with and without food allergies. Children with asthma, with (n = 22) and (n = 53) without food allergies were included. All subjects were classified according to the GINA guidelines (2009) and had received at least 3 months of anti-inflammatory therapy prior to testing. Fractional exhaled nitric oxide and sputum differential counts were performed using standard techniques.   Children with asthma and food allergies had significantly higher fractional exhaled nitric oxide median (range) [(22.4 (6.1-86.9) vs. 10.3 (2.7-38.7) (p = 0.01)] and sputum eosinophil percentage [15.5 (5.0-53.0) vs. 2.0 (0-20) (p allergies. These results suggest that the children with asthma and food allergies have increased eosinophilic inflammation of the airways. © 2011 John Wiley & Sons A/S.

The effect of hepatocyte growth factor on secretory functions in human eosinophils.

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Yamauchi, Yumiko; Ueki, Shigeharu; Konno, Yasunori; Ito, Wataru; Takeda, Masahide; Nakamura, Yuka; Nishikawa, Junko; Moritoki, Yuki; Omokawa, Ayumi; Saga, Tomoo; Hirokawa, Makoto

2016-12-01

Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro-fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study. We found that HGF significantly inhibited IL-5-induced secretion of TGF-β and VEGF from human eosinophils. The inhibitory effect is not associated with TGF-β transcription; rather, it is associated with ultrastructural granule emptying and loss of intracellular TGF-β contents, indicating HGF inhibits the process of piecemeal degranulation. The effect of HGF on extracellular trap cell death (ETosis) that mediates cytolytic degranulation was also investigated; however, immobilized IgG- or phorbol myristate acetate-induced ETosis was only minimally attenuated by HGF. These results reveal the effect of HGF on the distinct pathways of eosinophil secretory functions and also provide novel insights into the role of HGF in the pathogenesis of allergic inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Translation and cultural adaptation of the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS v2.0).

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Santos, Maria Fernanda Oliveira; Barros, Cristina Palmer; Silva, Carlos Henrique Martins da; Paro, Helena Borges Martins da Silva

2017-11-04

To translate and culturally adapt the Pediatric Eosinophilic Esophagitis Symptom Score (version 2.0), a tool used to assess pediatric eosinophilic esophagitis symptoms reported by patients and/or their parents/caregivers. The Pediatric Eosinophilic Esophagitis Symptom Score was translated through the following stages: initial translation, back-translation, and consensus of independent reviewers through the Delphi technique. The pre-final version of the Pediatric Eosinophilic Esophagitis Symptom Score was applied to five 8-to-18-year-old patients and to ten parents of two-to-18-year-old patients from an outpatient pediatric gastroenterology service (pre-test). During the translation process, no translations presenting with difficult consensus in the review process or grammar inconsistencies were observed. During the pre-test, difficulties in comprehension of some unconventional terms, e.g., "náusea", were observed. Adverbs of frequency, such as "quase nunca" were also identified as being of difficult understanding by patients and parents, and the substitution by the term "raramente" was suggested. Such difficulties may be inherent to the pediatric age group. Age 8 years or above should be considered adequate for the self-reporting of symptoms. The study presents the Brazilian version of the Pediatric Eosinophilic Esophagitis Symptom Score, which is adapted to the Brazilian culture. This version may be introduced as a clinical and research tool for the assessment of patients with esophagic disease symptoms. The Pediatric Eosinophilic Esophagitis Symptom Score is a breakthrough in the evaluation of symptoms of pediatric eosinophilic esophagitis, since it reinforces the importance of self-reporting by patients who experience this disease. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Coccidioidomycosis Masquerading as Eosinophilic Ascites.

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Alavi, Kourosh; Atla, Pradeep R; Haq, Tahmina; Sheikh, Muhammad Y

2015-01-01

Endemic to the southwestern parts of the United States, coccidioidomycosis, also known as "Valley Fever," is a common fungal infection that primarily affects the lungs in both acute and chronic forms. Disseminated coccidioidomycosis is the most severe but very uncommon and usually occurs in immunocompromised individuals. It can affect the central nervous system, bones, joints, skin, and, very rarely, the abdomen. This is the first case report of a patient with coccidioidal dissemination to the peritoneum presenting as eosinophilic ascites (EA). A 27-year-old male presented with acute abdominal pain and distention from ascites. He had eosinophilia of 11.1% with negative testing for stool studies, HIV, and tuberculosis infection. Ascitic fluid exam was remarkable for low serum-ascites albumin gradient (SAAG), PMN count >250/mm(3), and eosinophils of 62%. Abdominal imaging showed thickened small bowel and endoscopic testing negative for gastric and small bowel biopsies. He was treated empirically for spontaneous bacterial peritonitis, but no definitive diagnosis could be made until coccidioidal serology returned positive. We noted complete resolution of symptoms with oral fluconazole during outpatient follow-up. Disseminated coccidioidomycosis can present in an atypical fashion and may manifest as peritonitis with low SAAG EA. The finding of EA in an endemic area should raise the suspicion of coccidioidal dissemination.

Churg-Strauss syndrome with coexistence of eosinophilic vasculitis, granulomatous phlebitis and granulomatous dermatitis in bullous pemphigoid-like blisters.

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Ishibashi, Masafumi; Kudo, Saori; Yamamoto, Kyoko; Shimai, Nobuko; Chen, Ko-Ron

2011-03-01

The main histopathological features in the cutaneous lesions of Churg-Strauss syndrome (CSS) are dermal leukocytoclastic vasculitis with a variable eosinophilic infiltrate and non-vasculitic tissue eosinophilia with granuloma formation. This wide histopathological spectrum may account for the various skin manifestations of CSS. However, the unique histopathological combination of dermal eosinophilic vasculitis and subcutaneous granulomatous phlebitis accompanied by bulla formation has not been previously described. We report an unusual CSS case showing dermal necrotizing eosinophilic vasculitis and granulomatous phlebitis in purpuric lesions coupled with subepidermal blistering. The blisters showed dermal granulomatous dermatitis and eosinophilia without evidence of vasculitis. Dermal necrotizing eosinophilic vasculitis was characterized by fibrinoid alteration of the vessel wall, a prominent perivascular eosinophilic infiltrate, a few infiltrating histiocytes along the affected vessel wall, and the absence of neutrophilic infiltration. The underlying subcutaneous granulomatous phlebitis was characterized by an angiocentric histiocytic infiltrate surrounded by marked eosinophilic infiltrate. Deposition of cytotoxic proteins and radicals derived from eosinophils in the vessel walls and papillary dermis followed by a secondary granulomatous response may account for the unique clinical and histopathological features in this case. Copyright © 2010 John Wiley & Sons A/S.

Bach2 Controls Homeostasis of Eosinophils by Restricting the Type-2 Helper Function of T Cells.

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Sato, Yuki; Kato, Hiroki; Ebina-Shibuya, Risa; Itoh-Nakadai, Ari; Okuyama, Ryuhei; Igarashi, Kazuhiko

2017-03-01

Bach2 is a transcription factor which represses its target genes and plays important roles in the differentiation of B and T lymphoid cells. Bach2-deficient (KO) mice develop severe pulmonary alveolar proteinosis, which is associated with increased numbers of granulocytes and T cells. Bach2 is essential for the regulation of T cells, but its role in the regulation of granulocytes is not clear. Here, we observed increased numbers of eosinophils but not neutrophils in the bone marrow, spleen, peripheral blood, and bronchoalveolar lavage fluids of Bach2 KO mice compared with those of wild-type (WT) mice. Upon co-transplantation of the bone marrow cells from CD45.2 Bach2 KO and CD45.1/CD45.2 double-positive WT mice to irradiated WT CD45.1/CD45.2 mice, the reconstituted numbers of eosinophils were similar between Bach2 KO and WT cells. These results showed that the deficiency of Bach2 in eosinophils did not directly drive the differentiation of eosinophils. To investigate the effect of Bach2 KO CD4 + T cells upon eosinophils, we analyzed Rag2/Bach2-double deficient (dKO) mice which lack lymphocytes including CD4 + T cells. Rag2/Bach2 dKO mice did not show any increase in the numbers of eosinophils. Importantly, Bach2 KO mice showed an increase of interleukin-5 (Il-5) in the sera compared with WT mice. These results suggest that up-regulated functions of CD4 + T cells including secretion of Il-5 resulted in proliferation and/or migration to peripheral tissues of eosinophils in Bach2 KO mice. We propose that Bach2 controls homeostasis of eosinophils via restricting the production of Il-5 in CD4 + T cells.

Ascites in a Young Woman: A Rare Presentation of Eosinophilic Gastroenteritis

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Carina Santos

2018-01-01

Full Text Available Introduction. Eosinophilic gastroenteritis (EGE is a rare idiopathic disease that can affect one or more organs of the digestive tract. It has an estimated incidence of 1–20 cases per 100,000 patients. Klein et al. classified EGE into 3 subtypes: predominant mucosal, muscular, or subserosal. Clinical Case. We report a case of a 32-year-old woman, who presented with diffuse abdominal pain, nausea, postprandial infarction, diarrhea, and moderate ascites of three-week evolution. The rest of physical examination did not show alterations. The past medical history was unremarkable. Laboratory test results revealed peripheral blood eosinophilia. Abdominal CT scan revealed diffuse and concentric parietal thickening of the distal 2/3 of esophagus, moderate volume ascites, and small bowel wall thickening and distension on the left quadrants. The paracentesis revealed 93.3% of eosinophils. The colon biopsies evidenced an increase in the number of eosinophils. Secondary causes of eosinophilia were excluded. The patient was treated with oral prednisolone 40 mg/day with immediate clinical and analytical improvement. Conclusion. Eosinophilic gastroenteritis is a rare condition with a nonspecific and highly variable clinical presentation, which requires a high level of clinical suspicion. It is a diagnosis of exclusion. Secondary causes of eosinophilia such as intestinal tuberculosis, parasitosis, and malignant neoplasms should be excluded.

Optimal therapy and prospects for new medicines in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

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Pagnoux, Christian; Groh, Matthieu

2016-10-01

The prevalence of eosinophilic granulomatosis with polyangiitis (EGPA; previously known as Churg-Strauss syndrome) is lower than that of other antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV's), and only a few randomized controlled trials have been conducted for this rare disease. However, recent international efforts have helped delineate the best treatment approach. At present, EGPA conventional therapy is by default similar to that of other AAVs. Limited, non-severe EGPA can initially be treated with glucocorticoids (GCs) alone. Patients with life-threatening manifestations and/or major organ involvement must receive a combination of GCs and an immunosuppressant, mainly cyclophosphamide. Remission can be achieved in >85% of patients with these first-line treatments, but vasculitis relapses occur in more than one-third of patients, and about 85% cannot stop GC treatment because of GC-dependent asthma and/or ENT manifestations. A few biologic agents, including rituximab or mepolizumab, are now under investigation after interesting preliminary results. Expert commentary: Treatment for EGPA still has several unmet needs. Several biologic agents are now under investigation in randomized controlled trials, but a few others should be considered soon. Their benefit should be demonstrated for devising more EGPA-tailored therapeutic strategies (ideally GC-free).

In vitro study of histamine and histamine receptor ligands influence on the adhesion of purified human eosinophils to endothelium.

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Grosicki, Marek; Wójcik, Tomasz; Chlopicki, Stefan; Kieć-Kononowicz, Katarzyna

2016-04-15

It is a well-known fact that histamine is involved in eosinophil-dependent inflammatory responses including cellular chemotaxis and migration. Nevertheless, the relative role of histamine receptors in the mechanisms of eosinophils adhesion to endothelial cells is not known. Therefore the aim of presented study was to examine the effect of selective histamine receptors ligands on eosinophils adhesion to endothelium. For that purpose the highly purified human eosinophils have been isolated from the peripheral blood. The viability and functional integrity of isolated eosinophils have been validated in several tests. Histamine as well as 4-methylhistamine (selective H4 agonist) in concentration-dependent manner significantly increased number of eosinophils that adhere to endothelium. Among the selective histamine receptors antagonist or H1 inverse agonist only JNJ7777120 (histamine H4 antagonist) and thioperamide (dual histamine H3/H4 antagonist) had direct effect on eosinophils adhesion to endothelial cells. Antagonists of H1 (diphenhydramine, mepyramine) H2 (ranitidine and famotidine) and H3 (pitolisant) histamine receptors were ineffective. To the best of our knowledge, this is the first study to demonstrate that histamine receptor H4 plays a dominant role in histamine-induced eosinophils adhesion to endothelium. Copyright © 2016 Elsevier B.V. All rights reserved.

The distribution of blood eosinophil levels in a Japanese COPD clinical trial database and in the rest of the world

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Barnes N

2018-02-01

Full Text Available Neil Barnes,1,2 Takeo Ishii,3,4 Nobuyuki Hizawa,5 Dawn Midwinter,6 Mark James,3 Emma Hilton,1 Paul Jones1,71Respiratory Medicine Franchise, GlaxoSmithKline, Brentford, UK; 2William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK; 3Medical Affairs, GlaxoSmithKline K.K., Tokyo, Japan; 4Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; 5Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; 6Global Respiratory Department, GlaxoSmithKline, Stockley Park, UK; 7Institute of Infection and Immunity, St George’s University of London, London, UK Background: Blood eosinophil measurements may help to guide physicians on the use of inhaled corticosteroids (ICS for patients with chronic obstructive pulmonary disease (COPD. Emerging data suggest that COPD patients with higher blood eosinophil counts may be at higher risk of exacerbations and more likely to benefit from combined ICS/long-acting beta2-agonist (LABA treatment than therapy with a LABA alone. This analysis describes the distribution of blood eosinophil count at baseline in Japanese COPD patients in comparison with non-Japanese COPD patients.Methods: A post hoc analysis of eosinophil distribution by percentage and absolute cell count was performed across 12 Phase II–IV COPD clinical studies (seven Japanese studies [N=848 available absolute eosinophil counts] and five global studies [N=5,397 available eosinophil counts] that included 246 Japanese patients resident in Japan with available counts. Blood eosinophil distributions were assessed at baseline, before blinded treatment assignment.Findings: Among Japanese patients, the median (interquartile range absolute eosinophil count was 170 cells/mm3 (100–280 cells/mm3. Overall, 612/1,094 Japanese patients (56% had an absolute eosinophil count ≥150 cells/mm3 and 902/1,304 Japanese patients (69% had a percentage eosinophil ≥2%. Among non

Chronic Eosinophilic Leukemia—Not Otherwise Specified (NOS in the Background of a Large Cell Lymphoma

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Wilson I. Gonsalves

2013-01-01

Full Text Available Clonal eosinophilic disorders are rare among hematological malignancies. Most eosinophilia tends to be due to secondary causes such as infections, hypersensitivity conditions, drug reactions, and connective tissue disorders. The presence of a primary clonal eosinophilic disorder such as chronic eosinophilic leukemia—not otherwise specified (NOS in the presence of a synchronous large cell lymphoma—is rare making the diagnosis challenging. We present a case of a 51-year-old female with the aforementioned presentation and demonstrate the extensive workup performed to identify the diagnosis.

Investigation of CT diagnostic imaging of 'Eosinophilic chronic rhinosinusitis'

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Ogino, Nobuhiro; Matsuwaki, Yoshinori; Ojiri, Hiroya; Kanou, Asami; Fukuda, Kunihiko

2011-01-01

'Eosinophilic chronic rhinosinusitis (ECRS)' is a newly developed entity of chronic rhinosinusitis, which shows resistance against conventional treatment and poor prognosis. Pathologically, ECRS is manifested by high-degree of eosinophilic infiltration in the paranasal sinus mucosa. We structure the CT diagnostic criteria of ECRS and assess its availability. This diagnostic criteria consists of disease distribution (bilateral and predominant in the ethmoid sinus), existence of nasal polyp (s) and high attenuation which suggestive of allergic mucine. We retrospectively review CT of clinically diagnosed 14 ECRS cases to see if CT features of each case fit the criteria or not. The current CT diagnostic criteria of ECRS were proven to be useful to evaluate cases with clinical suspicion of ECRS. (author)

Cytoplasmic influence of nucleolar development

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Ghosh, Sibdas

1974-01-01

The role of cytoplasmic factors on the development of nucleolus in nucleus has been investigated in Ehrlich mouse ascites tumour cells using tritiated thymidine/uridine for autoradiography. It is inferred from the observations that the cytoplasmic factors has some but not absolute control over the development of nucleolus. (M.G.B.)

[Eosinophilic esophagitis, a pathology on the rise].

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Miranda García, M; Gutiérrez Teira, B

2013-10-01

The eosinophilic esofagitis is a pathology that consists of an inflammatory condition of the esophagus, which is characterized for having a high percentage of eosinophils. It is a problem of allergic origin and his diagnosis is increasing in the population, especially in children and adult young persons, throughout last decade. The fisiopathology is not completely established nowadays. The diagnosis is confirmed with endoscopia and capture of biopsies. The differential diagnosis is necessary to be done with the disease for reflux gastroesofágico, gastroenteritis eosinofílica, by Crohn's disease, pathology of connective fabric, syndrome hipereosinofílico, infections and response of hypersensitivity to medicaments. Nowadays there is no a treatment that is definitive. We present a clinical case, which was valued initially for the consultation of Primary care. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Pulmonary infiltration with eosinophils in 14 dogs

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Corcoran, B.M.; Thoday, K.L.; Henfrey, J.I.; Simpson, J.W.; Burnie, A.G.; Mooney, C.T.

1991-01-01

Pulmonary infiltration with eosinophils was diagnosed in 14 dogs, whose age ranged from three months to 13 years. The predominant clinical sign was coughing. Dyspnoea, tachypnoea and pruritus were also observed. An absolute circulating eosinophilia was seen in eight dogs and basophilia in five dogs. Thoracic radiographic changes were variable and were not diagnostic. Bronchoscopic evidence of mild to severe bronchitis was present in 12 dogs. Abnormal numbers of eosinophils were found in bronchoalveolar lavage samples and, or, bronchial washings in all 14 cases, but no significant bacteria were recovered. Respiratory compliance was measured in five dogs and was abnormal in three. Faecal examination for helminth parasites was carried out in four cases, a large ascarid burden being identified in one. Intradermal skin testing was carried out in three dogs but was negative in all cases. Complete remission of signs was achieved with prednisolone in 12 cases with six dogs requiring continuous or repeated treatment. Three dogs died as a direct consequence of progression of the disease

Time-dependent labelling course of human eosinophilic granulocytes after 3H thymidine application

International Nuclear Information System (INIS)

Walle, A.J.

1975-01-01

After intravenous injection of 0.1 μCi/g body weight 3 H-Thymidine and taking of blood samples in intervals of 6-12 hrs. on three test persons with healthy blood, the labelling course of the eosinophilic granulocytes was studied. The cells were classified in four groups, according to the relative frequency of the different degrees of labelling. The time-dependent labelling index curves showed a nawe-sheped course. Elimination of the eosinophilics from the blood is carried out according to the 'At-random'-principle. 12 hrs. p.i. already 10% of the eosinophilics in the blood were labelled with maximally 5 grains. The cell flow-in phase of 13 hrs. was succeeded by a flow-out phase of nearly the same duration, afthr the first labelling maximum of 17%. 80 hrs. p.i. the first massive in-flow of high-labelled cells containing more than 30 grains. After reaching the labelling maximum of 58%, the labelling index values decreased continuously. Until the 11th day p.i., appr. 50% of the eosinophilics were still labelled, after 17 days appr. 25%, more than 65% of which consisted of cells with only 2-4 grains. Comparison of the labelling index curves of the grain groups with each other shows at first a synchronous, then an increasingly asynchronous course, according to the desynchronization of the several eosinophilic generation cycles in the bone marrow which gets more significant in the course of time. (orig.) [de

Products of neutrophils and eosinophils increase the responsiveness of human isolated bronchial tissue.

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Hallahan, A R; Armour, C L; Black, J L

1990-05-01

This study examines the possibility that products of neutrophils and eosinophils could increase the responsiveness of human isolated bronchial tissue. Neutrophils and eosinophils were isolated from the peripheral blood of healthy volunteers. The cells were incubated with 1 microM calcium ionophore A23187 for 10-15 min then centrifuged, the supernatant collected and stored at -70 degrees C. Human bronchial rings (2-3 mm diameter, 3-4 mm long) were prepared from specimens resected at thoracotomy. The tissues were suspended in organ baths under a 1 g load and changes in tension measured isometrically. Stable contractions to bolus doses of histamine (0.1-10 microM) or to electrical field stimulation (40-100 V, 4-16 Hz, 1 ms for 20 s) were established. Supernatant from 106 neutrophils or 105 eosinophils was then added and tissue responsiveness reassessed. Neutrophil supernatant increased tissue responsiveness to histamine and electrical field stimulation by 54 +/- 17% (n = 5, p less than 0.05) and 18 +/- 7% (n = 6, p less than 0.05), respectively. Eosinophil supernatant increased the histamine response by 60 +/- 23% (n = 8, p less than 0.05) while tissue responsiveness to electrical field stimulation was unchanged (n = 3). Thus, as neutrophils and eosinophils can change the responsiveness of human bronchus in vitro it is possible that they do this in vivo and may not simply be temporally related to the development of bronchial hyperresponsiveness.

Resveratrol induces cell cycle arrest and apoptosis in human eosinophils from asthmatic individuals.

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Hu, Xin; Wang, Jing; Xia, Yu; Simayi, Mihereguli; Ikramullah, Syed; He, Yuanbing; Cui, Shihong; Li, Shuang; Wushouer, Qimanguli

2016-12-01

Eosinophils exert a number of inflammatory effects through the degranulation and release of intracellular mediators, and are considered to be key effector cells in allergic disorders, including asthma. In order to investigate the regulatory effects of the natural polyphenol, resveratrol, on eosinophils derived from asthmatic individuals, the cell counting Kit‑8 assay and flow cytometry analysis were used to determine cell proliferation and cell cycle progression in these cells, respectively. Cellular apoptosis was detected using annexin V-fluorescein isothiocyanate/propidium iodide double‑staining. The protein expression levels of p53, p21, cyclin‑dependent kinase 2 (CDK2), cyclin A, cyclin E, Bim, B‑cell lymphoma (Bcl)‑2 and Bcl‑2‑associated X protein (Bax) were measured by western blot analysis following resveratrol treatment. The results indicated that resveratrol effectively suppressed the proliferation of eosinophils from asthmatic patients in a concentration‑ and time‑dependent manner. In addition, resveratrol was observed to arrest cell cycle progression in G1/S phase by increasing the protein expression levels of p53 and p21, and concurrently reducing the protein expression levels of CDK2, cyclin A and cyclin E. Furthermore, resveratrol treatment significantly induced apoptosis in eosinophils, likely through the upregulation of Bim and Bax protein expression levels and the downregulation of Bcl‑2 protein expression. These findings suggested that resveratrol may be a potential agent for the treatment of asthma by decreasing the number of eosinophils.

In vivo changes of hemopoietic progenitors and the expression of the interleukin 5 gene in eosinophilic mice infected with Toxocara canis.

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Yamaguchi, Y; Matsui, T; Kasahara, T; Etoh, S; Tominaga, A; Takatsu, K; Miura, Y; Suda, T

1990-12-01

It has been demonstrated that purified recombinant interleukin 5 (rIL-5) supports the terminal differentiation and proliferation of eosinophilic precursors in vitro and plays an important role in increasing the functional activities of eosinophils. In this study, we examined the hemopoietic changes and analyzed murine (m) IL-5 mRNA expression in eosinophilic mice infected with the helminth Toxocara canis. In eosinophilic mice, eosinophils increased in number in both bone marrow and spleen. However, the number of eosinophilic precursors increased markedly in spleen cells of eosinophilic mice but remained relatively constant in the bone marrow. In the presence of granulocyte colony-stimulating factor (G-CSF), the number of granulocytic precursors increased in the spleen cells of eosinophilic mice. From these findings, the condition of eosinophilopoiesis in eosinophilic mice is accompanied by an increase in granulocyte-macrophage progenitors as well as eosinophil progenitors. Using Northern blot analysis, a weak but definite band corresponding to mIL-5 mRNA was detected in spleen cells of mice 4 and 5 days after helminthic infection. In addition, these data were confirmed by in vitro polymerase chain reaction (PCR) amplification of mRNA obtained from these spleen cells. Finally, injections of a monoclonal antibody against mIL-5 completely suppressed the blood eosinophilia in mice infected with T. canis. In conclusion, IL-5 is suggested to play a major role in eosinophilopoiesis in vivo.

Histamine 1 Receptor Blockade Enhances Eosinophil-Mediated Clearance of Adult Filarial Worms.

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Ellen Mueller Fox

Full Text Available Filariae are tissue-invasive nematodes that cause diseases such as elephantiasis and river blindness. The goal of this study was to characterize the role of histamine during Litomosoides sigmodontis infection of BALB/c mice, a murine model of filariasis. Time course studies demonstrated that while expression of histidine decarboxylase mRNA increases throughout 12 weeks of infection, serum levels of histamine exhibit two peaks-one 30 minutes after primary infection and one 8 weeks later. Interestingly, mice treated with fexofenadine, a histamine receptor 1 inhibitor, demonstrated significantly reduced worm burden in infected mice compared to untreated infected controls. Although fexofenadine-treated mice had decreased antigen-specific IgE levels as well as lower splenocyte IL-5 and IFNγ production, they exhibited a greater than fourfold rise in eosinophil numbers at the tissue site where adult L. sigmodontis worms reside. Fexofenadine-mediated clearance of L. sigmodontis worms was dependent on host eosinophils, as fexofenadine did not decrease worm burdens in eosinophil-deficient dblGATA mice. These findings suggest that histamine release induced by tissue invasive helminths may aid parasite survival by diminishing eosinophilic responses. Further, these results raise the possibility that combining H1 receptor inhibitors with current anthelmintics may improve treatment efficacy for filariae and other tissue-invasive helminths.

Seborrheic inclusion cyst of the skin positive for cytoplasmic inclusion bodies and HPV antigen.

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Terada, Tadashi

2012-01-01

Seborrheic inclusion cyst (SIC) is a very rare variant of epidermal cyst of the skin. SIC shows seborrheic keratosis (SK)-like lesion in epidermal cyst. SIC is extremely rare; only 6 case reports have been published in the English literature. However, no immunohistochemical study of SIC has been reported. A 41-year-old Japanese man noticed a subcutaneous tumor in the neck. Physical examination showed slightly mobile tumor in the subcutaneous tissue, and total excision was performed. Grossly, the tumor (1 x 1 x 0.8 cm) was cyst containing atheromatous keratin. Microscopically, the lesion is a cyst containing keratins. About one half of the cyst showed features of epidermal cyst consisting of mature squamous epithelium with granular layers. The other one half showed SK-like epidermal proliferation. The SK-like area showed basaloid cell proliferation with pseudohorn cysts. No significant atypia was noted. Many eosinophilic cytoplasmic inclusion bodies were noted in the SK-like area. Immunohistochemically, the SK-like area was positive for pancytokeratin AE1/3, pancytokeratin CAM5.2, p63, and Ki-67 (labeling=8%) and HPV, but negative for p53. The pathological diagnosis was SIC.

A Case of Unifocal Eosinophilic Granuloma of the Mandible in an Adult Female: A Case Report

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Anshita Agarwal

2012-01-01

Full Text Available Eosinophilic granuloma of bone is a disease with an incidence of one new case per 350,000 to 2 million per year, which is an uncommon disease of maxillofacial region, and presents in more than 90% in children under the age of ten with predominance for males. As a result, eosinophilic granuloma of the jaw is always unconsidered in the differential diagnosis of similar lesions by many clinicians. It is difficult to make a correct diagnosis on it without proof of a pathological diagnosis, which correlates with the diverse clinical and radiographic presentations of eosinophilic granuloma in the jaws. In the present paper we report a rare case of unifocal eosinophilic granuloma of mandible occurring in an adult female.

Characterization of a receptor for interleukin-5 on human eosinophils and the myeloid leukemia line HL-60

International Nuclear Information System (INIS)

Ingley, E.; Young, I.G.

1991-01-01

Interleukin-5 (IL-5) promotes the growth and differentiation of human eosinophils and may regulate the selective eosinophilia and eosinophil activation seen in certain diseases. Radiolabeled recombinant human IL-5 (hIL-5) was used to characterize the IL-5 receptor present on normal human eosinophils and on the myeloid leukemia line HL-60, which can be induced to differentiate into eosinophilic cells. Binding studies with eosinophils and HL-60 cells grown under alkaline conditions demonstrated similar high-affinity binding sites for hIL-5 on both cell types with kd values of approximately 400 pmol/L. The binding observed was specific in that it was not inhibited by hIL-3, human granulocyte-macrophage colony-stimulating factor, or hIL-2. Binding studies with a number of other human cell lines, including a B-lymphoma line, and with lymphocyte and neutrophil preparations were also performed, but IL-5 receptors were not detectable on these cells. The number of hIL-5 receptors on HL-60 cells could be correlated with its propensity to differentiate towards an eosinophilic cell type. Expression of hIL-5 receptors on HL-60 cells was upregulated by butyric acid under alkaline conditions, downregulated by hIL-3, virtually eliminated by dimethyl sulfoxide and hIL-5, while hIL-2 had no detectable effect. One major 125I-hIL-5-crosslinked complex of 75 to 85 Kd in Mr was detected on HL-60 cells using crosslinking agents giving a molecular mass of 55 to 60 Kd for the hIL-5 receptor itself. Studies using cellular autoradiography showed that IL-5 receptors were evenly distributed on eosinophils but that receptor distribution on HL-60 cells was noticeably heterogeneous. Eosinophils were the only cells in slides prepared from peripheral blood that had detectable levels of IL-5 receptors in agreement with the specific action of IL-5 on the human eosinophil lineage

Lactoferrin, myeloperoxidase, lysozyme and eosinophil cationic protein in exudate in delayed type hypersensitivity

DEFF Research Database (Denmark)

Lerche, A; Bisgaard, H; Christensen, J D

1988-01-01

allergic patients with nickel challenge in the chamber medium showed a time-dependent increase of mononuclear cells, eosinophils and basophils and a concomitant decrease of polymorphonuclear granulocytes, characteristic of a combined specific and unspecific inflammation. The morphology of the exudate...... in contact allergic patients exposed to nickel showed a dominance of polymorphonuclear granulocytes throughout the study period, while mononuclear cells, eosinophils and basophils were detected at a much lower quantity and with a considerable delay. Further, we studied the kinetics of the leucocyte granule...... proteins: lactoferrin, myeloperoxidase, lysozyme and eosinophil cationic protein in exudate fluid in a parallel test. A significant higher flux was found for all during the second day of allergen exposure compared to contact allergic patients without allergen challenge as well as normal volunteers...

Hypoxia causes IL-8 secretion, Charcot Leyden crystal formation, and suppression of corticosteroid-induced apoptosis in human eosinophils.

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Porter, L M; Cowburn, A S; Farahi, N; Deighton, J; Farrow, S N; Fiddler, C A; Juss, J K; Condliffe, A M; Chilvers, E R

2017-06-01

Inflamed environments are typically hypercellular, rich in pro-inflammatory cytokines, and profoundly hypoxic. While the effects of hypoxia on neutrophil longevity and function have been widely studied, little is known about the consequences of this stimulus on eosinophils. We sought to investigate the effects of hypoxia on several key aspects of eosinophil biology, namely secretion, survival, and their sensitivity to glucocorticosteroids (GCS), agents that normally induce eosinophil apoptosis. Eosinophils derived from patients with asthma/atopy or healthy controls were incubated under normoxia and hypoxia, with or without glucocorticoids. Activation was measured by flow cytometry, ELISA of cultured supernatants, and F-actin staining; apoptosis and efferocytosis by morphology and flow cytometry; and GCS efficacy by apoptosis assays and qPCR. Hypoxic incubation (3 kPa) caused (i) stabilization of HIF-2α and up-regulation of hypoxia-regulated genes including BNIP3 (BCL2/adenovirus E1B 19-kDa protein-interacting protein 3) and GLUT1 (glucose transporter 1); (ii) secretion of pre-formed IL-8, and Charcot Leyden crystal (CLC) formation, which was most evident in eosinophils derived from atopic and asthmatic donors; (iii) enhanced F-actin formation; (iv) marked prolongation of eosinophil lifespan (via a NF-κB and Class I PI3-kinase-dependent mechanism); and (v) complete abrogation of the normal pro-apoptotic effect of dexamethasone and fluticasone furoate. This latter effect was evident despite preservation of GCS-mediated gene transactivation under hypoxia. These data indicate that hypoxia promotes an eosinophil pro-inflammatory phenotype by enhancing eosinophil secretory function, delaying constitutive apoptosis, and importantly, antagonizing the normal pro-apoptotic effect of GCS. As eosinophils typically accumulate at sites that are relatively hypoxic, particularly during periods of inflammation, these findings may have important implications to understanding the

Changes in CD11b and L-selectin expression on eosinophils are mediated by human lung fibroblasts in vitro

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Spoelstra, FM; Hovenga, H; Noordhoek, JA; Postma, DS; Kauffman, HF

Eosinophilic airway infiltration is a central feature in asthma. Eosinophils recovered from bronchoalveolar fluid show an activated phenotype, e.g., increased CD11b and decreased L-selectin expression. We investigated whether lung fibroblasts are able to activate eosinophils in vitro, and if so,

Eosinophils subvert host resistance to an intracellular pathogen by instigating non-protective IL-4 in CCR2-/- mice.

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Verma, A H; Bueter, C L; Rothenberg, M E; Deepe, G S

2017-01-01

Eosinophils contribute to type II immune responses in helminth infections and allergic diseases; however, their influence on intracellular pathogens is less clear. We previously reported that CCR2 -/- mice exposed to the intracellular fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an early exaggerated interleukin (IL)-4 response. We sought to identify the cellular source promulgating IL-4 in infected mutant animals. Eosinophils were the principal instigators of non-protective IL-4 and depleting this granulocyte population improved fungal clearance in CCR2 -/- animals. The deleterious impact of eosinophilia on mycosis was also recapitulated in transgenic animals overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed that phagocytosis of H. capsulatum via the pattern recognition receptor complement receptor (CR) 3 triggered the heightened IL-4 response in murine eosinophils. This phenomenon was conserved in human eosinophils; exposure of cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings elucidate a detrimental attribute of eosinophil biology in fungal infections that could potentially trigger a collapse in host defenses by instigating type II immunity.

CT-guided corticosteroid injection for solitary eosinophilic granuloma of the spine

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Rimondi, Eugenio; Rossi, Giuseppe [Istituto Ortopedico Rizzoli, University of Bologna, Department of Radiology and Interventional Angiographic Radiology, Bologna (Italy); Mavrogenis, Andreas F. [Istituto Ortopedico Rizzoli, University of Bologna, Department of Orthopedics, Bologna (Italy); Istituto Ortopedico Rizzoli, University of Bologna, Department of Orthopaedics, Orthopaedic Oncology Service, Bologna (Italy); Ussia, Giuseppe; Angelini, Andrea [Istituto Ortopedico Rizzoli, University of Bologna, Department of Orthopedics, Bologna (Italy); Ruggieri, Pietro [Istituto Ortopedico Rizzoli, University of Bologna, Department of Orthopedics, Bologna (Italy); Istituto Ortopedico Rizzoli, University of Bologna, Department of Orthopaedics, Bologna (Italy)

2011-06-15

To evaluate the clinical and imaging outcome of patients with symptomatic eosinophilic granuloma of the spine treated with CT-guided intralesional methylprednisolone injection after biopsy. Patients (n =19) with symptomatic solitary eosinophilic granuloma of the spine treated by CT-guided intralesional methylprednisolone injection were retrospectively studied. There were 12 males and seven females with a mean age of 17 years (range, 3-43 years). The mean follow-up was 6 years (median, 4 years; range, 0.5-19 years). Spinal location included the cervical (two patients), thoracic (seven patients), lumbar spine (eight patients), and the sacrum (two patients). Vertebra plana was observed in two patients. All patients had biopsies before treatment. Complete resolution of pain and healing of the lesion was observed in 17 patients (89.5%); none of these patients had recurrence at the latest examination. Reconstitution of the T1 and L1 vertebra plana was observed in both patients. Two patients initially diagnosed and treated for a solitary eosinophilic granuloma had constant pain after the procedure; in these patients, 6 and 12 months after the procedure, respectively, imaging showed multifocal disease and systemic therapy was administered. Complications related to the procedure were not observed. General anesthesia was administered in two patients because of intolerable pain during the procedure. In view of the benign clinical course of eosinophilic granuloma, in patients with symptomatic lesions, CT-guided intralesional corticosteroid injection is a safe and effective outpatient treatment with a low complication rate. (orig.)

Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1-PDGFRα

International Nuclear Information System (INIS)

Ishihara, Kenji; Kitamura, Hajime; Hiraizumi, Kenji; Kaneko, Motoko; Takahashi, Aki; Zee, OkPyo; Seyama, Toshio; Hong, JangJa; Ohuchi, Kazuo; Hirasawa, Noriyasu

2008-01-01

The constitutively activated tyrosine kinase Fip1-like 1 (FIP1L1)-platelet-derived growth factor receptor α (PDGFRα) causes eosinophilic leukemia EoL-1 cells to proliferate. Recently, we demonstrated that histone deacetylase inhibitors suppressed this proliferation and induced the differentiation of EoL-1 cells into eosinophils in parallel with a decrease in the level of FIP1L1-PDGFRα. In this study, we analyzed the mechanism by which FIP1L1-PDGFRα induces the proliferation and whether the suppression of cell proliferation triggers the differentiation into eosinophils. The FIP1L1-PDGFRα inhibitor imatinib inhibited the proliferation of EoL-1 cells and decreased the level of the oncoprotein c-Myc as well as the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK). The proliferation of EoL-1 cells and expression of c-Myc were also inhibited by the MEK inhibitor U0126 and JNK inhibitor SP600125. The expression of the eosinophilic differentiation marker CCR3 was not induced by imatinib. These findings suggest that FIP1L1-PDGFRα induces the proliferation of EoL-1 cells through the induction of c-Myc expression via ERK and JNK signaling pathways, but is not involved in the inhibition of differentiation toward mature eosinophils

[Increased expressions of substance P and neurokinin/tachykinin receptor 1 in eosinophils of patients with psoriasis].

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Zuo, Zhe; Wang, Junling; Zhang, Huiyun; Zheng, Wenjiao; Zhang, Zenan; He, Shaoheng

2017-07-01

Objective To investigate the expressions of substance P (SP) and its receptor neurokinin/tachykinin receptor 1 (NK1R) in peripheral blood eosinophils of patients with psoriasis. Methods The levels of SP and NK1R in the peripheral blood of both patients with psoriasis and healthy people were detected by flow cytometry. This method was again used to detect the levels of SP and NK1R in the peripheral blood eosinophils of patients with psoriasis after stimulated with the crude extracts of Artemisia pollen, dust mite and Platanus pollen (all at concentrations of 0.1 and 1.0 μg/mL). Results Compared with the healthy controls, the percentages of SP + and NK1R + eosinophils in psoriasis patients increased up to 2.7 and 0.5 folds, respectively. Moreover, the mean fluorescence intensity (MFI) of SP + and NK1R + eosinophils of psoriasis patients were elevated by 1.5 and 0.2 folds, respectively. The percentage of SP + eosinophils in psoriasis were down-regulated by 60% after the stimulation with Platanus pollen extract (1 μg/mL), while 0.1 μg/mL Platanus pollen extract induced a 0.6-fold increase in the percentage of NK1R + eosinophis. Conclusion The expressions of SP and NK1R are up-regulated in peripheral blood eosinophils of patients with psoriasis.

Heightened systemic levels of neutrophil and eosinophil granular proteins in pulmonary tuberculosis and reversal following treatment.

Science.gov (United States)

Moideen, Kadar; Kumar, Nathella Pavan; Nair, Dina; Banurekha, Vaithilingam V; Bethunaickan, Ramalingam; Babu, Subash

2018-04-09

Granulocytes are activated during tuberculosis (TB) infection and act as immune effector cells and granulocyte responses are implicated in TB pathogenesis. Plasma levels of neutrophil and eosinophil granular proteins provide an indirect measure of degranulation. In this study, we wanted to examine the levels of neutrophil and eosinophil granular proteins in individuals with pulmonary tuberculosis (PTB) and to compare them with the levels in latent TB (LTB) individuals. Hence, we measured the plasma levels of myeloperoxidase (MPO), neutrophil elastase, and proteinase-3; major basic protein (MBP), eosinophil derived neurotoxin (EDN), eosinophil cationic protein (ECP) and eosinophil peroxidase (EPX) in these individuals. Finally, we also measured the levels of all of these parameters in PTB individuals following anti-tuberculosis (ATT) treatment. Our data reveal that PTB individuals are characterized by significantly higher plasma levels of MPO, elastase, human proteinase 3 as well as MBP and EDN in comparison to LTB individuals. Our data also reveal that ATT resulted in reversal of all of these changes, indicating an association with TB disease. Finally, our data show that the systemic levels of MPO and proteinase-3 can significantly discriminate PTB from LTB individuals. Thus, our data suggest that neutrophil and eosinophil granular proteins could play a potential role in the innate immune response and therefore, the pathogenesis of pulmonary TB. Copyright © 2018 American Society for Microbiology.

Characterization and antagonism of cytokine-induced eosinophil priming

NARCIS (Netherlands)

Rosas Rosas, Ana Marcela

2006-01-01

Allergic asthma is an inflammatory disease characterized by bronchial hyper-responsiveness, airway inflammation, and reversible obstruction of the airways. In humans, cytokine activated eosinophils are thought to be important players in this process since they can release inflammatory mediators

Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides

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Peter Lamprecht

2018-04-01

Full Text Available Anti-neutrophil cytoplasmic autoantibodies (ANCA targeting proteinase 3 (PR3 and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA, microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV.

Coccidioidomycosis Masquerading as Eosinophilic Ascites

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Kourosh Alavi

2015-01-01

Full Text Available Endemic to the southwestern parts of the United States, coccidioidomycosis, also known as “Valley Fever,” is a common fungal infection that primarily affects the lungs in both acute and chronic forms. Disseminated coccidioidomycosis is the most severe but very uncommon and usually occurs in immunocompromised individuals. It can affect the central nervous system, bones, joints, skin, and, very rarely, the abdomen. This is the first case report of a patient with coccidioidal dissemination to the peritoneum presenting as eosinophilic ascites (EA. A 27-year-old male presented with acute abdominal pain and distention from ascites. He had eosinophilia of 11.1% with negative testing for stool studies, HIV, and tuberculosis infection. Ascitic fluid exam was remarkable for low serum-ascites albumin gradient (SAAG, PMN count >250/mm3, and eosinophils of 62%. Abdominal imaging showed thickened small bowel and endoscopic testing negative for gastric and small bowel biopsies. He was treated empirically for spontaneous bacterial peritonitis, but no definitive diagnosis could be made until coccidioidal serology returned positive. We noted complete resolution of symptoms with oral fluconazole during outpatient follow-up. Disseminated coccidioidomycosis can present in an atypical fashion and may manifest as peritonitis with low SAAG EA. The finding of EA in an endemic area should raise the suspicion of coccidioidal dissemination.

Evaluation of plasma eosinophil count and mean platelet volume in patients with coronary slow flow

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Mehmet Demir

2014-01-01

Full Text Available OBJECTIVE: The pathophysiology of coronary slow flow has not been clearly defined, although multiple abnormalities including arteritis, endothelial dysfunction, and atherothrombosis, have been reported. It is known that eosinophils play an important role in inflammation, endothelial dysfunction, and thrombosis. We aimed to compare the eosinophil counts of coronary slow flow patients versus healthy controls. METHODS: This study included 50 coronary slow flow patients (19 males, mean age 65.6±13.7 years and 30 healthy controls (10 males, mean age 57.86±11.6 years. These participants were evaluated using concurrent routine biochemical tests as well as neutrophil, lymphocyte, and eosinophil counts and mean platelet volume (MPV, which were obtained from the whole blood count. These parameters were compared between groups. RESULTS: The baseline characteristics of the study groups were comparable. The coronary slow flow patients had a higher mean platelet volume and eosinophil count than the control group (8.38±0.86 vs 6.28±1.6 fL and 0.31±0.42 vs 0.09±0.05; p<0.001 and 0.008, respectively. CONCLUSION: Our study demonstrated a relationship between eosinophil count and MPV in patients with coronary slow flow.

Multiple intra-abdominal serosal myxosarcomas in two koalas (Phascolarctos cinereus).

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Astudillo, V González; Schaffer-White, A; Allavena, R; Palmieri, C

2015-01-01

Two adult koalas (Phascolarctos cinereus) were presented for necropsy examination without any clinical history. A diffuse, severe gelatinous effusion was found in the abdominal cavity, while numerous 1-3 mm diameter, round, well-demarcated, multifocal to coalescing, raised, firm nodules containing a clear gelatinous fluid were scattered on the surface of the parietal peritoneum, diaphragm, liver, gastrointestinal tract and mesentery. Microscopically, the nodular lesions consisted of spindle-shaped to stellate neoplastic cells, with scant eosinophilic cytoplasm and moderate anisocytosis and anisokaryosis. The neoplastic cells were admixed with and surrounded by abundant acellular pale eosinophilic material that was stained by Alcian blue and only weakly by the periodic acid-Schiff reaction. Serosal proliferations are described rarely in koalas and to the authors' knowledge this is the first reported case of serosal myxosarcoma. The significance and pathogenesis of this condition in the koala population is unknown. Copyright © 2015 Elsevier Ltd. All rights reserved.

Eosinophilic myositis resulted from Sarcocystis infection in prime marbled beef of Japanese black cattle

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Tohru Kimura

Full Text Available Partial changes of color (greenish to brownish were found in prime marbled beef of Japanese black cattle. The disseminated lesions of the skeletal muscles were histopathologically examined in relation to Sarcocystis infection. The lesions in the muscles showed granulomas with inflammatory cell infiltration. The sarcocysts had a distinct wall, which was radically striated by palisading villar protrusions. The sarcocyst wall was surrounded by degenerative eosinophils and necrotic muscle fibers. In conclusion, eosinophilic myositis in prime marbled beef of Japanese black cattle resulted from Sarcocystis spp. infection. The muscular lesions were characterized by the presence of granulomas and capsulated sarcocysts surrounded by numerous eosinophils. [Vet. World 2011; 4(11.000: 500-502

Eosinophils in the lung – modulating apoptosis and efferocytosis in airway inflammation

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Jennifer M Felton

2014-07-01

Full Text Available Due to the key role of the lung in efficient transfer of oxygen in exchange for carbon dioxide, a controlled inflammatory response is essential for restoration of tissue homeostasis following airway exposure to bacterial pathogens or environmental toxins. Unregulated or prolonged inflammatory responses in the lungs can lead to tissue damage, disrupting normal tissue architecture and consequently compromising efficient gaseous exchange. Failure to resolve inflammation underlies the development and/or progression of a number of inflammatory lung diseases including asthma. Eosinophils, granulocytic cells of the innate immune system, are primarily involved in defence against parasitic infections. However, the propagation of the allergic inflammatory response in chronic asthma is thought to involve excessive recruitment and impaired apoptosis of eosinophils together with defective phagocytic clearance of apoptotic cells (efferocytosis. In terms of therapeutic approaches for treatment of asthma, the widespread use of glucocorticoids is associated with a number of adverse health consequences after long-term use, while some patients suffer from steroid-resistant disease. A new approach for therapeutic intervention would be to promote the resolution of inflammation via modulation of eosinophil apoptosis and the phagocytic clearance of apoptotic cells. This review focuses on the mechanisms underpinning eosinophil-mediated lung damage, currently available treatments and therapeutic targets that might in future be harnessed to facilitate inflammation resolution by the manipulation of cell survival and clearance pathways.

Central Role of IL-23 and IL-17 Producing Eosinophils as Immunomodulatory Effector Cells in Acute Pulmonary Aspergillosis and Allergic Asthma.

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Guerra, Evelyn Santos; Lee, Chrono K; Specht, Charles A; Yadav, Bhawna; Huang, Haibin; Akalin, Ali; Huh, Jun R; Mueller, Christian; Levitz, Stuart M

2017-01-01

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with conidia. All of these functions underscore a potential protective role for eosinophils in acute aspergillosis. Given the postulated role for IL-17 in asthma pathogenesis, we assessed whether eosinophils could act as sources of IL-23 and IL-17 in models where mice were sensitized to either A. fumigatus antigens or ovalbumin (OVA). We found IL-23p19+ IL-17AF+ eosinophils in both allergic models. Moreover, close to 95% of IL-23p19+ cells and >90% of IL-17AF+ cells were identified as eosinophils. These data establish a new paradigm in acute and allergic aspergillosis whereby eosinophils act not only as effector cells but also as immunomodulatory cells driving the IL-23/IL-17 axis and contributing to inflammatory cell recruitment.

Cytoplasmic Streaming - Skylab Student Experiment ED-63

Science.gov (United States)

1973-01-01

This chart describes the Skylab student experiment (ED-63), Cytoplasmic Streaming, proposed by Cheryl A. Peitz of Arapahoe High School, Littleton, Colorado. Experiment ED-63 was to observe the effect of zero-gravity on cytoplasmic streaming in the aquatic plant named Elodea, commonly called water weed or water thyme. The phenomenon of cytoplasmic streaming is not well understood, but it is recognized as the circulation mechanism of the internal materials or cytoplasm of a cell. Cytoplasm is a gelatinous substance that has the ability to change its viscosity and flow, carrying various cell materials with it. The activity can be stimulated by sunlight or heat. In March 1972, NASA and the National Science Teachers Association selected 25 experiment proposals for flight on Skylab. Science advisors from the Marshall Space Flight Center aided and assisted the students in developing the proposals for flight on Skylab.

Osseous eosinophilic granuloma in children; Le granulome eosinophile des os chez l'enfant

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Leblan, I.; Gaucher, H.; Marinard, L.; Galloy, M.A.; Phi, I.N.; Hoeffel, J.C. [Hopital de Brabois-Vandoeuvre, 54 - Nancy (France). Service de radiologie

2001-02-01

Eosinophilic granuloma of bone or Langerhans cell histiocytosis is mostly uni-focal. It appears on plain X Ray as a solitary destructive lesion of long bones or flat bones. CT is useful to define the extension to the cortical bone and also to precisely localize the lesion when the anatomy is complex (hip, spine, base of the skull). MR is very useful in case of more aggressive lesions when there is extension to soft tissues. Differential diagnosis includes circumscribed osteitis and tumors prognosis is more serious in case of multiple lesions. (authors)

The analysis of imaging diagnosis and misdiagnosis of vertebral eosinophilic granuloma

International Nuclear Information System (INIS)

Liang Weiqiang; Li Sheng

2007-01-01

Objective: To analyze the imaging features of vertebral eosinophilic granuloma and the reasons of misdiagnosis, so as to improve the diagnosis accuracy of the disease. Methods: The clinical materials and images findings of 10 patients with vertebral eosinophilic granuloma proved by surgery and histopathology were analyzed retrospectively. Results: Of all the cases, 3 of them were located in cervical vertebra, 5 in thoracic vertebra and 2 in lumbar vertebra. 8 lesions were single and 2 involved the adjacent 2 vertebrae. 4 lesions showed obvious sinking and flattening of the vertebra body, with widening anteroposterior and transverse diameters, 4 cases showed wedge-shaped appearance, 2 cases showed well-defined oval deossification. The appendix of vertebrae in 3 lesions were destroyed with surrounding mass. The intervertebral spaces were normal in 7 cases, slightly widened in 2 cases and slightly narrowed in 1 case. 6 cases showed paravertebra soft tissue swelling or soft tissue mass formation. Conclusion: Though there are some imaging features of vertebral eosinophilic granuloma, close combination with clinical dates and careful analysis of imaging findings can effectively improved the diagnosis accuracy. (authors)

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

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Anael Viana Pinto Alberto

Full Text Available 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.

Eosinophils express muscarinic receptors and corticotropin-releasing factor to disrupt the mucosal barrier in ulcerative colitis.

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Wallon, Conny; Persborn, Mats; Jönsson, Maria; Wang, Arthur; Phan, Van; Lampinen, Maria; Vicario, Maria; Santos, Javier; Sherman, Philip M; Carlson, Marie; Ericson, Ann-Charlott; McKay, Derek M; Söderholm, Johan D

2011-05-01

Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropin-releasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers ((51)Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), α-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Eosinophils are required to suppress Th2 responses in Peyer's patches during intestinal infection by nematodes.

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Strandmark, J; Steinfelder, S; Berek, C; Kühl, A A; Rausch, S; Hartmann, S

2017-05-01

Infections with enteric nematodes result in systemic type 2 helper T (Th2) responses, expansion of immunoglobulin (Ig)G1 antibodies, and eosinophilia. Eosinophils have a supportive role in mucosal Th2 induction during airway hyperreactivity. Whether eosinophils affect the local T-cell and antibody response in the gut-associated lymphoid tissue during enteric infections is unknown. We infected eosinophil-deficient ΔdblGATA-1 mice with the Th2-inducing small intestinal nematode Heligmosomoides polygyrus and found that parasite fecundity was decreased in the absence of eosinophils. A lack of eosinophils resulted in significantly augmented expression of GATA-3 and IL-4 by CD4 + T cells during acute infection, a finding strictly limited to Peyer's patches (PP). The increase in IL-4-producing cells in ΔdblGATA-1 mice was particularly evident within the CXCR5 + PD-1 + T-follicular helper cell population and was associated with a switch of germinal centre B cells to IgG1 production and elevated serum IgG1 levels. In contrast, infected wild-type mice had a modest IgG1 response in the PP, whereas successfully maintaining a population of IgA + germinal center B cells. Our results suggest a novel role for eosinophils during intestinal infection whereby they restrict IL-4 responses by follicular T helper cells and IgG1 class switching in the PP to ensure maintenance of local IgA production.

Phenotypic plasticity and targeting of Siglec-F(high) CD11c(low) eosinophils to the airway in a murine model of asthma.

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Abdala Valencia, H; Loffredo, L F; Misharin, A V; Berdnikovs, S

2016-02-01

Eosinophil recruitment in asthma is a multistep process, involving both trans-endothelial migration to the lung interstitium and trans-epithelial migration into the airways. While the trans-endothelial step is well studied, trans-epithelial recruitment is less understood. To contrast eosinophil recruitment between these two compartments, we employed a murine kinetics model of asthma. Eosinophils were phenotyped by multicolor flow cytometry in digested lung tissue and bronchoalveolar lavage (BAL) simultaneously, 6 h after each ovalbumin (OVA) challenge. There was an early expansion of tissue eosinophils after OVA challenge followed by eosinophil buildup in both compartments and a shift in phenotype over the course of the asthma model. Gradual transition from a Siglec-F(med) CD11c(-) to a Siglec-F(high) CD11c(low) phenotype in lung tissue was associated with eosinophil recruitment to the airways, as all BAL eosinophils were of the latter phenotype. Secondary microarray analysis of tissue-activated eosinophils demonstrated upregulation of specific integrin and chemokine receptor signature suggesting interaction with the mucosa. Using adhesion assays, we demonstrated that integrin CD11c mediated adhesion of eosinophils to fibrinogen, a significant component of epithelial barrier repair and remodeling. To the best of our knowledge, this is the only report to date dissecting compartmentalization of eosinophil recruitment as it unfolds during allergic inflammation. By capturing the kinetics of eosinophil phenotypic change in both tissue and BAL using flow cytometry and sorting, we were able to demonstrate a previously undocumented association between phenotypic shift of tissue-recruited eosinophils and their trans-epithelial movement, which implicates the existence of a specific mechanism targeting these cells to mucosal airways. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

TGF-Beta Gene Polymorphisms in Food Allergic versus Non-Food Allergic Eosinophilic Esophagitis

Science.gov (United States)

2013-10-01

esophageal dysfunction (i.e. dysphagia, anorexia, early satiety, failure to thrive) in whom gastro - esophageal reflux disease has been ruled out by...W81XWH-11-1-0741 TITLE: TGF-Beta Gene Polymorphisms in Food Allergic versus Non-Food Allergic Eosinophilic Esophagitis PRINCIPAL INVESTIGATOR...versus Non-Food Allergic Eosinophilic Esophagitis 5b. GRANT NUMBER W81XWH-11-1-0741 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David Broide MB

Elimination diets in the management of eosinophilic esophagitis

Directory of Open Access Journals (Sweden)

Wechsler JB

2014-05-01

Full Text Available Joshua B Wechsler, Sally Schwartz, Katie Amsden, Amir F Kagalwalla Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, IL, USA Abstract: Eosinophilic esophagitis, an increasingly recognized chronic inflammatory disorder isolated to the esophagus, is triggered by an abnormal allergic response to dietary antigens. Current treatment includes swallowed topical steroids and dietary modification, which aim to resolve symptoms and prevent long-term complications such as formation of strictures. The dietary approach has become more widely accepted because long-term steroid therapy is associated with potential risks. Dietary treatment includes elemental and elimination diets. An exclusive elemental diet, which requires replacement of all intact protein with amino acid-based formula, offers the best response of all available therapies, with remission in up to 96% of subjects proving it to be superior to all other available therapies including topical steroids. However, compliance with this approach is challenging because of poor taste and monotony. The high cost of formula and the associated psychosocial problems are additional drawbacks of this approach. Empiric and allergy test-directed elimination diets have gained popularity given that elimination of a limited number of foods is much easier and as such is more readily acceptable. There is a growing body of literature supporting this type of therapy in both children and adults. This paper reviews the evidence for all types of dietary therapy in eosinophilic esophagitis. Keywords: eosinophilic esophagitis, dietary therapy, empiric elimination, elemental, allergy test-directed

Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids

DEFF Research Database (Denmark)

Watz, Henrik; Tetzlaff, Kay; Wouters, Emiel F M

2016-01-01

were seen with eosinophil cutoffs of 300 cells per μL and 400 cells per μL, and mutually exclusive subgroups. INTERPRETATION: Blood eosinophil counts at screening were related to the exacerbation rate after complete ICS withdrawal in patients with severe to very severe COPD and a history...... of exacerbations. Our data suggest that counts of 4% or greater or 300 cells per μL or more might identify a deleterious effect of ICS withdrawal, an effect not seen in most patients with eosinophil counts below these thresholds. FUNDING: Boehringer Ingelheim....

Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor.

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Willart, M A M; van Nimwegen, M; Grefhorst, A; Hammad, H; Moons, L; Hoogsteden, H C; Lambrecht, B N; Kleinjan, A

2012-12-01

Ursodeoxycholic acid (UDCA) is the only known beneficial bile acid with immunomodulatory properties. Ursodeoxycholic acid prevents eosinophilic degranulation and reduces eosinophil counts in primary biliary cirrhosis. It is unknown whether UDCA would also modulate eosinophilic inflammation outside the gastrointestinal (GI) tract, such as eosinophilic airway inflammation seen in asthma. The working mechanism for its immunomodulatory effect is unknown. The immunosuppressive features of UDCA were studied in vivo, in mice, in an ovalbumin (OVA)-driven eosinophilic airway inflammation model. To study the mechanism of action of UDCA, we analyzed the effect of UDCA on eosinophils, T cells, and dendritic cell (DCs). DC function was studied in greater detail, focussing on migration and T-cell stimulatory strength in vivo and interaction with T cells in vitro as measured by time-lapse image analysis. Finally, we studied the capacity of UDCA to influence DC/T cell interaction. Ursodeoxycholic acid treatment of OVA-sensitized mice prior to OVA aerosol challenge significantly reduced eosinophilic airway inflammation compared with control animals. DCs expressed the farnesoid X receptor for UDCA. Ursodeoxycholic acid strongly promoted interleukin (IL)-12 production and enhanced the migration in DCs. The time of interaction between DCs and T cells was sharply reduced in vitro by UDCA treatment of the DCs resulting in a remarkable T-cell cytokine production. Ursodeoxycholic acid-treated DCs have less capacity than saline-treated DCs to induce eosinophilic inflammation in vivo in Balb/c mice. Ursodeoxycholic acid has the potency to suppress eosinophilic inflammation outside the GI tract. This potential comprises to alter critical function of DCs, in essence, the effect of UDCA on DCs through the modulation of the DC/T cell interaction. © 2012 John Wiley & Sons A/S.

Modulation of eosinophil generation and migration by Mangifera indica L. extract (Vimang).

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Sá-Nunes, Anderson; Rogerio, Alexandre P; Medeiros, Alexandra I; Fabris, Viciany E; Andreu, Gilberto P; Rivera, Dagmar G; Delgado, René; Faccioli, Lúcia H

2006-09-01

The effects of Vimang, an aqueous extract of the stem bark of Mangifera indica L. (Anacardiaceae), on cell migration in an experimental model of asthma was investigated. In vivo treatment of Toxocara canis-infected BALB/c mice for 18 days with 50 mg/kg Vimang reduced eosinophil migration into the bronchoalveolar space and peritoneal cavity. Also, eosinophil generation in bone marrow and blood eosinophilia were inhibited in infected mice treated with Vimang. This reduction was associated with inhibition of IL-5 production in serum and eotaxin in lung homogenates. In all these cases the effects of Vimang were more selective than those observed with dexamethasone. Moreover, Vimang treatment is not toxic for the animals, as demonstrated by the normal body weight increase during infection. These data confirm the potent anti-inflammatory effect of Vimang and support its potential use as an alternative therapeutic drug to the treatment of eosinophilic disorders including those caused by nematodes and allergic diseases.

Diagnostic value of eosinophils in pleural effusion: a prospective study of 26 cases.

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Matthai, Smita Mary; Kini, Usha

2003-02-01

Eosinophilic pleural effusions (EPFs), defined as the presence of 10% or more eosinophils in the pleural fluid, are relatively rare. Their diagnostic and prognostic significance, however, remains controversial, as most of the studies are based almost entirely on retrospective case studies. This prospective study examines 26 eosinophilic pleural effusions from among 444 consecutive pleural effusions investigated at this tertiary health care center from October 1999 to April 2002. This study was attempted to unravel the diagnostic and prognostic significance of these eosinophilic effusions and assess their clinical implications, if any. Koss and Light's criteria were applied in the analysis, which comprised macroscopic, biochemical, cytological, and microbiological examinations. Of the 26 EPFs studied, five were associated with tuberculosis and three with metastatic disease. Nineteen patients had significant associated lymphocytosis. Twenty-four patients have been followed up and are in good health to date and have had no recurrence of effusion. Thus, EPF could be associated with inflammatory, benign, and malignant conditions. Hence, a closer search for a definite etiological agent is warranted in the setting of such an effusion, especially in populations endemic for tuberculosis, as in a developing country like India and in populations with a high prevalence of malignancy. Copyright 2003 Wiley-Liss, Inc.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes

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Christie, Joshua R.; Beekman, Madeleine

2017-01-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes—specifically their organization into host cells and their uniparental (maternal) inheritance—enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller’s ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes—despite their asexual mode of reproduction—can readily undergo adaptive evolution. PMID:28025277

Eosinophilic Otitis Media: CT and MRI Findings and Literature Review

International Nuclear Information System (INIS)

Chung, Won Jung; Lee, Jeong Hyun; Lim, Hyun Kyung; Yoon, Tae Hyun; Cho, Kyung Ja; Baek, Jung Hwan

2012-01-01

Eosinophilic otitis media (EOM) is a relatively rare, intractable, middle ear disease with extremely viscous mucoid effusion containing eosinophils. EOM is associated with adult bronchial asthma and nasal allergies. Conventional treatments for otitis media with effusion (OME) or for chronic otitis media (COM), like tympanoplasty or mastoidectomy, when performed for the treatment of EOM, can induce severe complications such as deafness. Therefore, it should be differentiated from the usual type of OME or COM. To our knowledge, the clinical and imaging findings of EOM of temporal bone are not well-known to radiologists. We report here the CT and MRI findings of two EOM cases and review the clinical and histopathologic findings of this recently described disease entity.

Eosinophilic Otitis Media: CT and MRI Findings and Literature Review

Energy Technology Data Exchange (ETDEWEB)

Chung, Won Jung; Lee, Jeong Hyun; Lim, Hyun Kyung; Yoon, Tae Hyun; Cho, Kyung Ja; Baek, Jung Hwan [Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of)

2012-06-15

Eosinophilic otitis media (EOM) is a relatively rare, intractable, middle ear disease with extremely viscous mucoid effusion containing eosinophils. EOM is associated with adult bronchial asthma and nasal allergies. Conventional treatments for otitis media with effusion (OME) or for chronic otitis media (COM), like tympanoplasty or mastoidectomy, when performed for the treatment of EOM, can induce severe complications such as deafness. Therefore, it should be differentiated from the usual type of OME or COM. To our knowledge, the clinical and imaging findings of EOM of temporal bone are not well-known to radiologists. We report here the CT and MRI findings of two EOM cases and review the clinical and histopathologic findings of this recently described disease entity.

Simvastatin Inhibits IL-5-Induced Chemotaxis and CCR3 Expression of HL-60-Derived and Human Primary Eosinophils.

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Fu, Chia-Hsiang; Tsai, Wan-Chun; Lee, Ta-Jen; Huang, Chi-Che; Chang, Po-Hung; Su Pang, Jong-Hwei

2016-01-01

IL-5-induced chemotaxis of eosinophils is an important feature of allergic airway inflammatory diseases. Simvastatin, a lipid lowering agent, has been shown to exhibit anti-inflammatory and anti-allergic effects. Our aim was to investigate the effect of simvastatin on IL-5-induced eosinophil chemotaxis and its regulatory mechanisms. Eosinophils were derived by treating HL-60 clone 15 (HC15) cells with butyric acid (BA) in an alkaline condition or through direct isolation from human peripheral blood. The expressions of CC chemokine receptor 3 (CCR3) and interleukin (IL)-5 receptors (IL5Rα and β) were analyzed using RT/real-time PCR. The granular proteins were stained using fast green. Eotaxin-induced chemotaxis was measured using a transwell migration assay. CCR3 protein expression was revealed by immunocytochemistry. An animal model of allergic rhinitis was established by challenging Sprague-Dawley® rats repeatedly with ovalbumin. Butyric acid significantly increased the expression of IL5Rα and IL5Rβ, CCR3 and granular proteins in HC15 cells, indicating the maturation of eosinophils (BA-E cells). IL-5 further enhanced the CCR3 expression at both the mRNA and protein levels and the eotaxin-induced chemotaxis of BA-E cells. Simvastatin inhibited the effects of IL-5 on BA-E cells, but not in the presence of mevalonate. Similar results were also exhibited in human primary eosinophils. In vivo animal studies further confirmed that oral simvastatin could significantly suppress the infiltration of eosinophils into turbinate tissues of allergic rats. Therefore, simvastatin was demonstrated to inhibit IL-5-induced CCR3 expression and chemotaxis of eosinophils mediated via the mevalonate pathway. We confirmed that simvastatin also reduced eosinophilic infiltration in allergic rhinitis.

Molecular cloning of the human eosinophil-derived neurotoxin: A member of the ribonuclease gene family

International Nuclear Information System (INIS)

Rosenberg, H.F.; Tenen, D.G.; Ackerman, S.J.

1989-01-01

The authors have isolated a 725-base-pair cDNA clone for human eosinophil-derived neurotoxin (EDN). EDN is a distinct cationic protein of the eosinophil's large specific granule known primarily for its ability to induce ataxia, paralysis, and central nervous system cellular degeneration in experimental animals (Gordon phenomenon). The open reading frame encodes a 134-amino acid mature polypeptide with a molecular mass of 15.5 kDa and a 27-residue amino-terminal hydrophobic leader sequence. The sequence of the mature polypeptide is identical to that reported for human urinary ribonuclease, and to the amino-terminal sequence of human liver ribonuclease; the cDNA encodes a tryptophan in position 7. Both EDN and the related granule protein, eosinophil cationic protein, have ribonucleolytic activity; sequence similarities among EDN, eosinophil cationic protein, ribonucleases from liver, urine, and pancreas, and angiogenin define a ribonuclease multigene family. mRNA encoding EDN was detected in uninduced HL-60 cells and was up-regulated in cells induced toward eosinophilic differentiation with B-cell growth factor 2/interleukin 5 and toward neutrophilic differentiation with dimethyl sulfoxide. EDN mRNA was detected in mature neutrophils even though EDN-like neurotoxic activity is not found neutrophil extracts. These results suggest that neutrophils contain a protein that is closely related or identical to EDN

Esophageal dilations in eosinophilic esophagitis: A single center experience

OpenAIRE

Ukleja, Andrew; Shiroky, Jennifer; Agarwal, Amitesh; Allende, Daniela

2014-01-01

AIM: To diagnose the clinical and histologic features that may be associated with or predictive of the need for dilation and dilation related complications; examine the safety of dilation in patients with eosinophilic esophagitis (EoE).

Eosinophilic Esophagitis in Two Patients with Systemic Sclerosis

Directory of Open Access Journals (Sweden)

Tracy M. Frech

2016-01-01

Full Text Available The gastrointestinal tract (GIT is the most common extracutaneous organ system damaged in systemic sclerosis (SSc and is the presenting feature in 10% of patients. The esophagus as the portion of the GIT is the most commonly affected and there is an association of gastroesophageal reflux (GER with SSc interstitial lung disease (ILD. Thus, an aggressive treatment for GER is recommended in all SSc patients with ILD; however, it is recognized that a long-term benefit to this treatment is needed to understand its impact. In this case report we discuss the presence of eosinophilic esophagitis (EoE in two SSc patients and discuss the role for early EGD in SSc patients with moderate-severe GER symptoms for tissue study. Assessment of esophageal biopsy specimens for the presence of eosinophils and possibly ANA can help elucidate disease pathogenesis and direct therapy, as the presence of EoE in SSc has important management considerations, particularly with regards to dietary modification strategies.

Cytoplasmic Estrogen Receptor in breast cancer

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Welsh, Allison W.; Lannin, Donald R.; Young, Gregory S.; Sherman, Mark E.; Figueroa, Jonine D.; Henry, N. Lynn; Ryden, Lisa; Kim, Chungyeul; Love, Richard R.; Schiff, Rachel; Rimm, David L.

2011-01-01

Purpose In addition to genomic signaling, it is accepted that ERα has non-nuclear signaling functions, which correlate with tamoxifen resistance in preclinical models. However, evidence for cytoplasmic ER localization in human breast tumors is less established. We sought to determine the presence and implications of non-nuclear ER in clinical specimens. Experimental Design A panel of ERα-specific antibodies (SP1, MC20, F10, 60c, 1D5) were validated by western blot and quantitative immunofluorescent (QIF) analysis of cell lines and patient controls. Then eight retrospective cohorts collected on tissue microarrays were assessed for cytoplasmic ER. Four cohorts were from Yale (YTMA 49, 107, 130, 128) and four others (NCI YTMA 99, South Swedish Breast Cancer Group SBII, NSABP B14, and a Vietnamese Cohort) from other sites around the world. Results Four of the antibodies specifically recognized ER by western and QIF, showed linear increases in amounts of ER in cell line series with progressively increasing ER, and the antibodies were reproducible on YTMA 49 with pearson’s correlations (r2 values)ranging from 0.87-0.94. One antibody with striking cytoplasmic staining (MC20) failed validation. We found evidence for specific cytoplasmic staining with the other 4 antibodies across eight cohorts. The average incidence was 1.5%, ranging from 0 to 3.2%. Conclusions Our data shows ERα present in the cytoplasm in a number of cases using multiple antibodies, while reinforcing the importance of antibody validation. In nearly 3,200 cases, cytoplasmic ER is present at very low incidence, suggesting its measurement is unlikely to be of routine clinical value. PMID:21980134

Eosinophilic Granulomatosis with Polyangiitis, formerly Churg-Strauss Syndrome (EGPA)

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... Strauss Syndrome (EGPA) Eosinophilic Granulomatosis with Polyangiitis, formerly Churg-Strauss Syndrome (EGPA) First Description Who gets EGPA (the “ ... granulomatosis with polyangiitis (EGP), formerly known as the Churg-Strauss Syndrome , is a systemic vasculitis. This disease was ...

Osseous eosinophilic granuloma in children

International Nuclear Information System (INIS)

Leblan, I.; Gaucher, H.; Marinard, L.; Galloy, M.A.; Phi, I.N.; Hoeffel, J.C.

2001-01-01

Eosinophilic granuloma of bone or Langerhans cell histiocytosis is mostly uni-focal. It appears on plain X Ray as a solitary destructive lesion of long bones or flat bones. CT is useful to define the extension to the cortical bone and also to precisely localize the lesion when the anatomy is complex (hip, spine, base of the skull). MR is very useful in case of more aggressive lesions when there is extension to soft tissues. Differential diagnosis includes circumscribed osteitis and tumors prognosis is more serious in case of multiple lesions. (authors)

Eosinophilic dermatosis of hematologic malignancy.

Science.gov (United States)

Martires, Kathryn; Callahan, Shields; Terushkin, Vitaly; Brinster, Nooshin; Leger, Marie; Soter, Nicholas A

2016-12-15

We report a 68-year-old woman with chroniclymphocytic leukemia, who developed numerous,pruritic, edematous, and vesicobullous skin lesionsof the face and extremities over the course of severalmonths. The diagnosis of eosinophilic dermatosis ofhematologic malignancy (EDHM) was made basedon the clinical history and histopathologic features.Owing to the possible link between EDHM and amore aggressive underlying CLL, she was startedagain on chemotherapy. This case serves as areminder that, although the precise pathogenesis ofEDHM remains unclear, the paraneoplastic disorderis the result of immune dysregulation. Patientswho develop EDHM should undergo prompthematologic/oncologic evaluation.

Angiostrongylus cantonensis eosinophilic meningitis: a clinical study of 42 consecutive cases in French Polynesia.

Science.gov (United States)

Oehler, Erwan; Ghawche, Frédéric; Delattre, Alex; Berberian, Anthony; Levy, Marc; Valour, Florent

2014-06-01

In endemic areas, eosinophilic meningitis is mainly caused by Angiostrongylus cantonensis. We describe a series of this poorly-known condition. Retrospective cohort study (2000-2012) including all patients diagnosed with eosinophilic meningitis in French Polynesia. Forty-two patients (males: 61.9%, age: 22 (IQR 17-32)) were diagnosed with a serologically proven (n=13) or probable A. cantonensis meningitis, mostly during the dry season (66.6%) and following the consumption of or prolonged contact with an intermediate/paratenic host (64.3%). No differential diagnosis was found in probable cases, in whom serological tests were performed earlier (7.5 days (6.5-10)) compared to positive patients (7.5 (6.5-10) versus 11 (7-30) days, p=0.02). The most commonly reported symptom was headache (92.8%). Fever (7.1%) and biological inflammatory syndrome (14.3%) were rare. Blood eosinophil count was 1200/mm(3) (900-2548). Cerebrospinal fluid (CSF) analysis disclosed a protein level of 0.9 g/L (0.7-1.1), a CSF/plasma glucose ratio of 0.50 (0.40-0.55), and 500 leucocytes/mm(3) (292-725; eosinophils: 42.0% (29.5-60); lymphocytes: 46.5% (32.5-59.0)). Thirteen cases (31.0%) were severe, with 11 focal neurological deficits. A delayed hospital referral (OR 1.13, p=0.05) was associated with severity. A. cantonensis meningitis must be evocated in young patients with meningitic syndrome, severe headache, and CSF inflammation with predominance of eosinophils. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The effect of omalizumab on eosinophilic inflammation of the respiratory tract in patients with allergic asthma.

Science.gov (United States)

Kupryś-Lipińska, Izabela; Molińska, Katarzyna; Kuna, Piotr

2016-01-01

Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses of these drugs, even when administered systemically. Transbronchial biopsies and bronchoalveolar lavage performed in patients with steroid-resistant asthma have demonstrated higher levels of eosinophils and Th2-type cytokines (IL-4 and IL-5) compared to steroid-sensitive patients. Clinical studies have confirmed that the very effective treatment in these cases is therapy with omalizumab - an anti-IgE monoclonal antibody. The paper discusses the efficacy of omalizumab in reducing eosinophil number in peripheral blood and in the airways of asthmatic patients based on basic, clinical, observational studies and case reports. The significance of omalizumab therapy in asthma control and mechanisms that regulate the effects of omalizumab on eosinophils are evaluated.

Cytoplasmic transduction peptide (CTP): New approach for the delivery of biomolecules into cytoplasm in vitro and in vivo

International Nuclear Information System (INIS)

Kim, Daeyou; Jeon, Choonju; Kim, Jeong-Hwan; Kim, Mi-Seon; Yoon, Cheol-Hee; Choi, In-Soo; Kim, Sung-Hoon; Bae, Yong-Soo

2006-01-01

The protein transduction domain (PTD) of HIV-1 TAT has been extensively documented with regard to its membrane transduction potential, as well as its efficient delivery of biomolecules in vivo. However, the majority of PTD and PTD-conjugated molecules translocate to the nucleus rather than to the cytoplasm after transduction, due to the functional nuclear localization sequence (NLS). Here, we report a cytoplasmic transduction peptide (CTP), which was deliberately designed to ensure the efficient cytoplasmic delivery of the CTP-fused biomolecules. In comparison with PTD, CTP and its fusion partners exhibited a clear preference for cytoplasmic localization, and also markedly enhanced membrane transduction potential. Unlike the mechanism underlying PTD-mediated transduction, CTP-mediated transduction occurs independently of the lipid raft-dependent macropinocytosis pathway. The CTP-conjugated Smac/DIABLO peptide (Smac-CTP) was also shown to be much more efficient than Smac-PTD in the blockage of the antiapoptotic properties of XIAP, suggesting that cytoplasmic functional molecules can be more efficiently targeted by CTP-mediated delivery. In in vivo trafficking studies, CTP-fused β-gal exhibited unique organ tropisms to the liver and lymph nodes when systemically injected into mice, whereas PTD-β-gal exhibited no such tropisms. Taken together, our findings implicate CTP as a novel delivery peptide appropriate for (i) molecular targeting to cytoplasmic compartments in vitro, (ii) the development of class I-associated CTL vaccines, and (iii) special drug delivery in vivo, without causing any untoward effects on nuclear genetic material

IL-3 maintains activation of the P90S6K/RPS6 pathway and increases translation in human eosinophils1

Science.gov (United States)

Esnault, Stephane; Kelly, Elizabeth A.B.; Shen, Zhong-Jian; Johansson, Mats W.; Malter, James S.; Jarjour, Nizar N.

2015-01-01

IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines IL-5, IL-3, and GM-CSF are typically present in atopic diseases including allergic asthma. Due to the functional redundancy of these 3 cytokines on eosinophils and the loss of IL-5 receptor on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these 3 cytokines signal through a common β-chain receptor, and yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce production of proteins such as semaphorin-7A without affecting mRNA level suggests a unique influence by IL-3 on translation. The purpose of this study is to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared to IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein (RP) S6 and the upstream kinase, p90S6K. Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared to circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations place IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. PMID:26276876

Arrest of cytoplasmic streaming induces algal proliferation in green paramecia.

Directory of Open Access Journals (Sweden)

Toshiyuki Takahashi

Full Text Available A green ciliate Paramecium bursaria, bearing several hundreds of endosymbiotic algae, demonstrates rotational microtubule-based cytoplasmic streaming, in which cytoplasmic granules and endosymbiotic algae flow in a constant direction. However, its physiological significance is still unknown. We investigated physiological roles of cytoplasmic streaming in P. bursaria through host cell cycle using video-microscopy. Here, we found that cytoplasmic streaming was arrested in dividing green paramecia and the endosymbiotic algae proliferated only during the arrest of cytoplasmic streaming. Interestingly, arrest of cytoplasmic streaming with pressure or a microtubule drug also induced proliferation of endosymbiotic algae independently of host cell cycle. Thus, cytoplasmic streaming may control the algal proliferation in P. bursaria. Furthermore, confocal microscopic observation revealed that a division septum was formed in the constricted area of a dividing paramecium, producing arrest of cytoplasmic streaming. This is a first report to suggest that cytoplasmic streaming controls proliferation of eukaryotic cells.

Cytoplasmic vitamin A binding proteins in chick embryo dermis and epidermis

International Nuclear Information System (INIS)

Gates, R.E.; King, L.E. Jr.

1985-01-01

Excess vitamin A has striking morphologic and developmental effects on chick embryo skin. While cytoplasmic retinoic acid-binding protein (CRABP) was known to be abundant in chick embryo skin, neither quantitative values nor the distribution between dermis and epidermis have been established. The authors determined CRABP levels in collagenase-separated dermis and epidermis from 8-day-old embryos using specific binding of all-trans-[11- 3 H]retinoic acid in cytosols prepared from gram quantities of these tissues. The level of CRABP in dermis was twice the level in epidermis whether calculated on the basis of wet weight, cytosol protein, or DNA. When averaged over many preparations, 3 times as much dermis as epidermis was recovered from a single piece of skin. Therefore, the dermis contained 85% of the extremely high CRABP levels found in collagenase-treated skin, while epidermis contributed only 15%. Cytoplasmic retinol binding protein (CRBP) was also detected in chick embryo skin, but the binding was low and the levels in epidermis and dermis were not significantly different. The amount of CRABP in chick embryo skin (1600 pmol/g wet weight or 100 pmol/mg cytosol protein) is the highest level reported in any tissue and suggests an important role for vitamin A in the normal development and maturation of skin

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes.

Science.gov (United States)

Christie, Joshua R; Beekman, Madeleine

2017-03-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes-specifically their organization into host cells and their uniparental (maternal) inheritance-enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller's ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes-despite their asexual mode of reproduction-can readily undergo adaptive evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Non-allergic activation of eosinophils after strenuous endurance ...

African Journals Online (AJOL)

Objective. To determine the effect of prolonged endurance exercise on the serum concentrations of eosinophil cationic protein (ECP), immunoglobulin E (IgE) and upper respiratory tract symptoms (URTS). Design. In 11 healthy, experienced volunteers (6 males, 5 females, age 43 ± 9.8 years) the serum concentrations of ...

IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils.

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Esnault, Stephane; Kelly, Elizabeth A B; Shen, Zhong-Jian; Johansson, Mats W; Malter, James S; Jarjour, Nizar N

2015-09-15

IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a result of the functional redundancy of these three cytokines on eosinophils and the loss of IL-5R on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these three cytokines signal through a common β-chain receptor but yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce the production of proteins, such as semaphorin-7A, without affecting mRNA levels suggests a unique influence of IL-3 on translation. The purpose of this study was to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared with IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF, or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein S6 (RPS6) and the upstream kinase 90-kDa ribosomal S6 kinase (p90S6K). Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared with circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations identify IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. Copyright © 2015 by The American Association of Immunologists, Inc.

Detection of eosinophilic myocarditis using contrast-enhanced magnetic resonance imaging: case report

International Nuclear Information System (INIS)

Takahashi, N.; Murakami, Y.; Shimada, T.; Kashima, Y.; Nakamura, K.; Inoue, S.-I.; Sugamori, T.; Katoh, H.; Ishibashi, Y.; Maruyama, R.

2001-01-01

Hypereosinophilic syndrome is characterized by idiopathic eosinophilia in the peripheral blood and multiorgan dysfunction secondary to mature eosinophil infiltration. It is essential to diagnose myocardial involvement in the early stage of the disease when active myocarditis due to cardiotoxic substances from eosinophils is still taking place, but clinical tools for the diagnosis of myocardial lesions in patients without overt cardiac dysfunction are not yet available. We present a case of successful detection of myocarditis due to hypereosinophilic syndrome by gadolinium-diethylenetriaminepentaascetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI). (author)

Detection of eosinophilic myocarditis using contrast-enhanced magnetic resonance imaging: case report

Energy Technology Data Exchange (ETDEWEB)

Takahashi, N.; Murakami, Y.; Shimada, T.; Kashima, Y.; Nakamura, K.; Inoue, S.-I.; Sugamori, T.; Katoh, H.; Ishibashi, Y. [Shimane Medical Univ., The Fourth Dept. of Internal Medicine, Izumo City, Shimane (Japan); Maruyama, R. [Shimane Medical Univ., Dept. of Laboratory Medicine, Izumo City, Shimane (Japan)

2001-02-01

Hypereosinophilic syndrome is characterized by idiopathic eosinophilia in the peripheral blood and multiorgan dysfunction secondary to mature eosinophil infiltration. It is essential to diagnose myocardial involvement in the early stage of the disease when active myocarditis due to cardiotoxic substances from eosinophils is still taking place, but clinical tools for the diagnosis of myocardial lesions in patients without overt cardiac dysfunction are not yet available. We present a case of successful detection of myocarditis due to hypereosinophilic syndrome by gadolinium-diethylenetriaminepentaascetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI). (author)

The effect of tributyltin on human eosinophilic [correction of eosinophylic] leukemia EoL-1 cells.

Science.gov (United States)

Sroka, Jolanta; Włosiak, Przemysław; Wilk, Anna; Antonik, Justyna; Czyz, Jarosław; Madeja, Zbigniew

2008-01-01

Organotin compounds are chemicals that are widely used in industry and agriculture as plastic stabilizers, catalysts and biocides. Many of them, including tributyltin (TBT), have been detected in human food and, as a consequence, detectable levels have been found in human blood. As organotin compounds were shown to possess immunotoxic activity, we focused our attention on the effect of TBT on the basic determinants of the function of eosinophils, i.e. cell adhesiveness and motility. We used human eosinophylic leukemia EoL-1 cells, a common in vitro cellular model of human eosinophils. Here, we demonstrate that TBT causes a dose-dependent decrease in the viability of EoL-1 cells. When administered at sub-lethal concentrations, TBT significantly decreases the adhesion of EoL-1 cells to human fibroblasts (HSFs) and inhibits their migration on fibroblast surfaces. Since the basic function of eosinophils is to invade inflamed tissues, our results indicate that TBT, and possibly other organotin compounds, may affect major cellular properties involved in the determination of in vivo eosinophil function.

Hyperandrogenism from an ovarian interstitial-cell tumor in an alpaca.

Science.gov (United States)

Gilbert, Rosanne; Kutzler, Michelle; Valentine, Beth A; Semevolos, Stacy

2006-11-01

An 8-year-old intact female Huacaya alpaca (Lama pacos) was presented for recent development of male behavior. Serum testosterone concentration was determined to be 969.1 pg/ml by using radioimmunoassay, while the range in 33 healthy female adult intact alpacas was 11.7-62.1 pg/ml. An ovarian mass was suspected, and an exploratory laparotomy was performed. A tan mass was present on the left ovary. Histologically, the mass was composed of closely packed, plump, polygonal cells with central round nuclei with granular chromatin and abundant eosinophilic finely granular to vesiculate cytoplasm. An ovarian benign interstitial (Leydig) cell tumor was diagnosed.

Th2 cytokines and asthma — The role of interleukin-5 in allergic eosinophilic disease

Directory of Open Access Journals (Sweden)

Chapman Richard W

2001-03-01

Full Text Available Abstract Interleukin-5 is produced by a number of cell types, and is responsible for the maturation and release of eosinophils in the bone marrow. In humans, interleukin-5 is a very selective cytokine as a result of the restricted expression of the interleukin-5 receptor on eosinophils and basophils. Eosinophils are a prominent feature in the pulmonary inflammation that is associated with allergic airway diseases, suggesting that inhibition of interleukin-5 is a viable treatment. The present review addresses the data that relate interleukin-5 to pulmonary inflammation and function in animal models, and the use of neutralizing anti-interleukin-5 monoclonal antibodies for the treatment of asthma in humans.

Murine eosinophils labeled with indium-111 oxine: localization to delayed hypersensitivity reactions against a schistosomal antigen and to lymphokine in vivo

International Nuclear Information System (INIS)

Rand, T.H.; Clanton, J.A.; Runge, V.; English, D.; Colley, D.G.

1983-01-01

We have evaluated a method for quantitation of eosinophil migration to stimuli in vivo. Upon transfusion into normal syngeneic mice, 111In-labeled eosinophils had an intravascular half-life of 9.5 hr and distributed predominantly into spleen, bone marrow, and liver. In either Schistosoma mansoni-infected mice or recipients of lymphoid cells from infected mice, intradermal (ear pinna) injection of the schistosomal egg antigenic preparation (SEA) elicited time-dependent accumulation of 111In-labeled eosinophils detectable by either gamma scintillation counting of tissue samples or by nuclear medicine external imaging. Intradermal administration of a lymphokine fraction (containing eosinophil stimulation promoter activity) similarly caused accumulation of 111In-labeled eosinophils. Both reactions depended on the concentration of stimulus (SEA or lymphokine). 111In-labeled neutrophils or macrophages or 125I-albumin did not preferentially accumulate at the reactions examined to the extent found with 111In-labeled eosinophils, indicating that localization of label depends on an active process and is due to eosinophils rather than a contaminating cell type. The method was used to estimate how long eosinotactic lymphokine remained at dermal sites: 60% of initial activity was present 12 hr after injection. The model is discussed with regard to the role of lymphokines in hypersensitivity reactions with eosinophil involvement, such as the granulomatous response to S. mansoni eggs

Heart transplantation in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

Science.gov (United States)

Groh, Matthieu; Masciocco, Gabriella; Kirchner, Elizabeth; Kristen, Arnt; Pellegrini, Carlo; Varnous, Shaïda; Bortman, Guillermo; Rosenberg, Mark; Brucato, Antonio; Waterworth, Paul; Bonacina, Edgardo; Facchetti, Fabio; Calabrese, Leonard; Gregorini, Gina; Scali, Juan Jose; Starling, Randall; Frigerio, Maria; D'Armini, Andrea Maria; Guillevin, Loïc

2014-08-01

Heart involvement is the leading cause of death of patients with eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome) and is more frequent in anti-neutrophil cytoplasm antibody (ANCA)-negative patients. Post-transplant outcome has only been reported once. We conducted a retrospective international multicenter study. Patients satisfying the criteria of the American College of Rheumatology and/or revised Chapel Hill Consensus Conference Nomenclature were identified by collaborating vasculitis and transplant specialists, and the help of the Churg-Strauss Syndrome Association. Nine ANCA(-) patients who received transplants between October 1987 and December 2009 were identified. The vasculitis and cardiomyopathy diagnoses were concomitant for 5 patients and separated by 12 to 288 months for the remaining 4 patients. Despite ongoing immunosuppression, histologic examination of 7 (78%) patients' explanted hearts showed histologic patterns suggestive of active vasculitis. The overall 5-year survival rate was low (57%), but rose to 80% when considering only the 6 patients transplanted during the last decade. After survival lasting 3 to 60 months, 4 (44%) patients died sudden deaths. The search for EGPA-related cardiomyopathy is mandatory early in the course of this type of vasculitis. Indeed, prompt treatment with corticosteroids and cyclophosphamide may achieve restore cardiac function. Most patients in this series were undertreated. For patients with refractory EGPA, heart transplantation should be performed, which carries a fair prognosis. No optimal immunosuppressive strategy has yet been identified. Copyright © 2014 International Society for Heart and Lung Transplantation. All rights reserved.

Psychological distress in patients with morphea and eosinophilic fasciitis.

NARCIS (Netherlands)

Kroft, Ilse; Jong, E.M.G.J. de; Evers, A.W.M.

2009-01-01

OBJECTIVE: To examine the level of psychological distress and factors contributing to distress in patients with morphea or eosinophilic fasciitis. DESIGN: Cross-sectional study. SETTING: Dermatology outpatient clinic of a university hospital. PARTICIPANTS: Of 120 patients with morphea or

Eosinophils Subvert Host Resistance to an Intracellular Pathogen by Instigating Non-Protective IL-4 in CCR2−/− Mice

Science.gov (United States)

Verma, Akash H.; Bueter, Chelsea L.; Rothenberg, Marc E.; Deepe, George S.

2016-01-01

Eosinophils contribute to type II immune responses in helminth infections and allergic diseases, however, their influence on intracellular pathogens is less clear. We previously reported that CCR2−/− mice exposed to the intracellular fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an early exaggerated IL-4 response. We sought to identify the cellular source promulgating interleukin (IL)-4 in infected mutant animals. Eosinophils were the principal instigators of non-protective IL-4 and depleting this granulocyte population improved fungal clearance in CCR2−/− animals. The deleterious impact of eosinophilia on mycosis was also recapitulated in transgenic animals overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed that phagocytosis of H. capsulatum via the pattern recognition receptor complement receptor (CR) 3 triggered the heightened IL-4 response in murine eosinophils. This phenomenon was conserved in human eosinophils; exposure of cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings elucidate a detrimental attribute of eosinophil biology in fungal infections that could potentially trigger a collapse in host defenses by instigating type II immunity. PMID:27049063

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

DEFF Research Database (Denmark)

Sverrild, Asger; Bergqvist, Anders; Baines, Katherine J

2016-01-01

BACKGROUND: Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway...... tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell-associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol. METHODS: Airway hyperresponsiveness to inhaled mannitol was measured in 23 non......-smoking, corticosteroid-free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell-associated genes was measured by real-time PCR. RESULTS...

Eosinophilic enteritis – A diagnostic dilemma | Clegg-Lamptey ...

African Journals Online (AJOL)

It may mimic peptic ulcer, subacute (or chronic) intestinal obstruction, gastroenteritis, irritable bowel syndrome, and inflammatory bowel disease. The diagnosis is often ... Finalement laparotomy a revele des segments enflames de petit intestin, une biopsie de qui a montré Eosinophilic enteritis. Le malade a été traite par la ...

Antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis

NARCIS (Netherlands)

Kallenberg, Cees G. M.

Purpose of reviews This review focuses on recent advance in the diagnosis pathogenesis and treatment of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Recent findings Antineutrophil cytoplasmic autoantibodies are closely associated with Wegener's granulomatosis and

Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

NARCIS (Netherlands)

Cottin, Vincent; Bel, Elisabeth; Bottero, Paolo; Dalhoff, Klaus; Humbert, Marc; Lazor, Romain; Sinico, Renato A.; Sivasothy, Pasupathy; Wechsler, Michael E.; Groh, Matthieu; Marchand-Adam, Sylvain; Khouatra, Chahéra; Wallaert, Benoit; Taillé, Camille; Delaval, Philippe; Cadranel, Jacques; Bonniaud, Philippe; Prévot, Grégoire; Hirschi, Sandrine; Gondouin, Anne; Dunogué, Bertrand; Chatté, Gérard; Briault, Amandine; Jayne, David; Guillevin, Loïc; Cordier, Jean-François

2016-01-01

The respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) have not been studied in detail.In this retrospective multicentre study, EGPA was defined by asthma, eosinophilia and at least one new onset extra-bronchopulmonary organ manifestation of disease.The study

Proteomic analysis reveals strong mitochondrial involvement in cytoplasmic male sterility of pepper (Capsicum annuum L.).

Science.gov (United States)

Guo, Jinju; Wang, Peng; Cheng, Qing; Sun, Limin; Wang, Hongyu; Wang, Yutong; Kao, Lina; Li, Yanan; Qiu, Tuoyu; Yang, Wencai; Shen, Huolin

2017-09-25

Although cytoplasmic male sterility (CMS) is widely used for developing pepper hybrids, its molecular mechanism remains unclear. In this study, we used a high-throughput proteomics method called label-free to compare protein abundance across a pepper CMS line (A-line) and its isogenic maintainer line (B-line). Data are available via ProteomeXchange with identifier PXD006104. Approximately 324 differentially abundant protein species were identified and quantified; among which, 47 were up-accumulated and 140 were down-accumulated in the A-line; additionally, 75 and 62 protein species were specifically accumulated in the A-line and B-line, respectively. Protein species involved in pollen exine formation, pyruvate metabolic processes, the tricarboxylic acid cycle, the mitochondrial electron transport chain, and oxidative stress response were observed to be differentially accumulated between A-line and B-line, suggesting their potential roles in the regulation of pepper pollen abortion. Based on our data, we proposed a potential regulatory network for pepper CMS that unifies these processes. Artificial emasculation is a major obstacle in pepper hybrid breeding for its high labor cost and poor seed purity. While the use of cytoplasmic male sterility (CMS) in hybrid system is seriously frustrated because a long time is needed to cultivate male sterility line and its isogenic restore line. Transgenic technology is an effective and rapid method to obtain male sterility lines and its widely application has very important significance in speeding up breeding process in pepper. Although numerous studies have been conducted to select the genes related to male sterility, the molecular mechanism of cytoplasmic male sterility in pepper remains unknown. In this study, we used the high-throughput proteomic method called "label-free", coupled with liquid chromatography-quadrupole mass spectrometry (LC-MS/MS), to perform a novel comparison of expression profiles in a CMS pepper line

The molecular mechanism and physiological role of cytoplasmic streaming.

Science.gov (United States)

Tominaga, Motoki; Ito, Kohji

2015-10-01

Cytoplasmic streaming occurs widely in plants ranging from algae to angiosperms. However, the molecular mechanism and physiological role of cytoplasmic streaming have long remained unelucidated. Recent molecular genetic approaches have identified specific myosin members (XI-2 and XI-K as major and XI-1, XI-B, and XI-I as minor motive forces) for the generation of cytoplasmic streaming among 13 myosin XIs in Arabidopsis thaliana. Simultaneous knockout of these myosin XI members led to a reduced velocity of cytoplasmic streaming and marked defects of plant development. Furthermore, the artificial modifications of myosin XI-2 velocity changed plant and cell sizes along with the velocity of cytoplasmic streaming. Therefore, we assume that cytoplasmic streaming is one of the key regulators in determining plant size. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparative Analysis of Dibutyric cAMP and Butyric Acid on the Differentiation of Human Eosinophilic Leukemia EoL-1 Cells.

Science.gov (United States)

Jung, YunJae

2015-12-01

Purification of enough numbers of circulating eosinophils is difficult because eosinophils account for less than 5% peripheral blood leukocytes. Human eosinophilic leukemia EoL-1 cells have been considered an in vitro source of eosinophils as they can differentiate into mature eosinophil-like cells when incubated with dibutyryl cAMP (dbcAMP) or butyric acid. In this study, the viability and phenotypic maturation of EoL-1 cells stimulated by either dbcAMP or butyric acid were comparatively analyzed. After treatment with 100 µM dbcAMP or 0.5 µM butyric acid, EoL-1 cells showed morphological signs of differentiation, although the number of nonviable EoL-1 cells was significantly increased following butyric acid treatment. Stimulation of EoL-1 cells with 0.5 µM butyric acid more effectively induced the expression of mature eosinophil markers than stimulation with dbcAMP. These results suggest that treatment of EoL-1 cells with 0.5 µM butyric acid for limited duration could be an effective strategy for inducing their differentiation. Considering that expression of CCR3 was not sufficient in EoL-1 cells stimulated with 0.5 µM butyric acid, treatment of the chemically stimulated EoL-1 cells with cytokines, which primarily support eosinophil maturation, would help to obtain differentiated EoL-1 cells with greater functional maturity.

Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa

International Nuclear Information System (INIS)

Chou, Debbie L.; Gerriets, Joan E.; Schelegle, Edward S.; Hyde, Dallas M.; Miller, Lisa A.

2011-01-01

Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. -- Highlights: ► Ozone can modulate the localization of eosinophils in infant allergic airways. ► Expression of eotaxins within the lung is affected by ozone and allergen exposure. ► CCL24 induction by ozone and allergen exposure is not linked to eosinophilia.

Esophageal microbiome in eosinophilic esophagitis.

Directory of Open Access Journals (Sweden)

J Kirk Harris

Full Text Available 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.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.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.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.

Decrease of Airway Allergies After Lung Transplantation Is Associated With Reduced Basophils and Eosinophils.

Science.gov (United States)

Niedzwiecki, M; Yamada, Y; Inci, I; Weder, W; Jungraithmayr, W

2016-01-01

Allergies are hypersensitive reactions of the immune system on antigen exposure similar to immune reactions after transplantation (Tx). Their activity can change after Tx. The lung as a transplantable organ is challenged two-fold, by antigens from the blood and the air environment. Herein we analyzed if airway allergies change after lung Tx. We systematically reviewed patients' airway allergies before and after lung Tx between 1992 and 2014. The course of lymphocytes, thrombocytes, and leukocytes, among them neutrophils, eosinophils, and basophils, was analyzed in patients in whom airway allergies have changed and in whom they did not change. From 362 lung transplanted patients, 44 patients had suffered from allergies before Tx (12.2%). In 20 of these patients (45.5%), airway allergies disappeared completely within 1 year after lung Tx and were persistently absent thereafter. In these patients, basophils and eosinophils decreased significantly (P allergies did not disappear. Leukocytes overall, and in particular, neutrophils, decreased significantly in patients whose allergy disappeared (P allergies disappeared in almost half of cases after lung Tx. Along with this reduction, basophils and eosinophils decreased as potentially responsible cells for this phenomenon. These findings may stimulate intensified research on basophils and eosinophils as major drivers of airway allergies. Copyright © 2016 Elsevier Inc. All rights reserved.

Eosinophilic Esophagitis in Children from Western Saudi Arabia: Relative Frequency, Clinical, Pathological, Endoscopic, and Immunological Study

Directory of Open Access Journals (Sweden)

Omar I. Saadah

2012-01-01

Full Text Available Background and Purpose. Eosinophilic esophagitis (EE is an evolving allergic disease with an accelerated incidence. The purpose of this study was to delineate the relative frequency and clinicopathological characteristics of EE in children from western Saudi Arabia. Methods. Children with EE were studied retrospectively between October 2002 and December 2011 at King Abdulaziz University Hospital and International Medical Center. Results. The relative frequency of EE was 0.85% of 2127 upper gastrointestinal endoscopies performed during the study period. Eighteen patients were identified with EE. The median age was 8.6 years (range, 1.5–18 years. Thirteen (72.2% were males. Dysphagia and vomiting were the most common symptoms. Ten (55.6% children had history of atopy. Testing for food allergy by skin prick test was positive in 11 (61.1%. The most common endoscopic abnormalities were mucosal longitudinal furrow and loss of vascular pattern followed by patchy specks and strictures. The histopathological findings included increased intraepithelial eosinophils, eosinophilic degranulation, lamina propria fibrosis, and eosinophilic microabscesses. Treatment was initiated by swallowed topical corticosteroids in 12 (66.7% and oral prednisolone in 6 (33% patients, followed by low dose of topical corticosteroids and dietary elimination. Conclusions. Eosinophilic esophagitis is an uncommon but evolving problem. A high index of suspicion is required for early identifications and intervention to avoid possible complications.

Cytoplasmic chromatin triggers inflammation in senescence and cancer.

Science.gov (United States)

Dou, Zhixun; Ghosh, Kanad; Vizioli, Maria Grazia; Zhu, Jiajun; Sen, Payel; Wangensteen, Kirk J; Simithy, Johayra; Lan, Yemin; Lin, Yanping; Zhou, Zhuo; Capell, Brian C; Xu, Caiyue; Xu, Mingang; Kieckhaefer, Julia E; Jiang, Tianying; Shoshkes-Carmel, Michal; Tanim, K M Ahasan Al; Barber, Glen N; Seykora, John T; Millar, Sarah E; Kaestner, Klaus H; Garcia, Benjamin A; Adams, Peter D; Berger, Shelley L

2017-10-19

Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.

A 92-Year-Old Male with Eosinophilic Asthma Presenting with Recurrent Palpable Purpuric Plaques

Science.gov (United States)

Negbenebor, Nicole A.; Khalifian, Saami; Foreman, Ruth K.; Kroshinsky, Daniela

2018-01-01

Churg-Strauss syndrome or eosinophilic granulomatosis with polyangiitis is a systemic vasculitis affecting the small and medium-sized vasculature. It is commonly associated with asthma and eosinophilia. Most patients are diagnosed at around the age of 40. We report a case of biopsy-confirmed Churg-Strauss syndrome in a 92-year-old male with a history of eosinophilic asthma and peripheral eosinophilia who was later diagnosed with Churg-Strauss syndrome. PMID:29719830

A 92-Year-Old Male with Eosinophilic Asthma Presenting with Recurrent Palpable Purpuric Plaques

Directory of Open Access Journals (Sweden)

Nicole A. Negbenebor

2018-03-01

Full Text Available Churg-Strauss syndrome or eosinophilic granulomatosis with polyangiitis is a systemic vasculitis affecting the small and medium-sized vasculature. It is commonly associated with asthma and eosinophilia. Most patients are diagnosed at around the age of 40. We report a case of biopsy-confirmed Churg-Strauss syndrome in a 92-year-old male with a history of eosinophilic asthma and peripheral eosinophilia who was later diagnosed with Churg-Strauss syndrome.