ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2010
M. M. WALKER
Aliment Pharmacol Ther,31, 1229,1236 Summary Background, Allergy and functional gastrointestinal disorders have been associated with eosinophilia in duodenal mucosa. Aim, To assess the prevalence of eosinophilia in duodenal biopsies of patients attending for oesophogastroduodenoscopy and delineate associated clinical conditions. Methods, A total of 155 patients (mean age 55 years, 59% women) with normal duodenal biopsies were randomly selected for audit from histopathology files. Eosinophil counts in five high power fields (HPFs) were assessed. Records were analysed for symptoms, diagnosis and medications; patients were divided into five groups based on upper gastrointestinal (UGI) symptom profiles, including a control group of those without predominant UGI symptoms. The prevalence of duodenal eosinophilia (defined as >22/5HPFs a priori) was calculated. Results, In the control group, the mean duodenal eosinophil count was 15/5HPFs; prevalence of duodenal eosinophilia was 22.5%. In postprandial distress syndrome (PDS), both mean eosinophil counts (20.2/5HPF, P < 0.04) and prevalence of duodenal eosinophilia (47.3%, P < 0.04) were significantly higher. Duodenal eosinophilia was significantly associated with allergy (OR 5.04, 95% CI 2.12,11.95, P < 0.001). There was no association with irritable bowel syndrome or medications. Conclusions, Subtle duodenal eosinophilia is relatively common in routine oesophogastroduodenoscopy and previously overlooked; it is associated with allergy and may indicate a hypersensitivity mechanism in some patients with PDS including early satiety. [source]

Cellular characteristics of non-allergic eosinophilic conjunctivitis

ACTA OPHTHALMOLOGICA, Issue 2 2010
Osmo Kari
Abstract. Purpose:, This study examines the histology of conjunctival biopsy samples from patients with persistent allergic eosinophilic conjunctivitis (AEC) or non-allergic eosinophilic conjunctivitis (NAEC). Methods:, Fourteen patients with conjunctivitis and eosinophilia in cytology samples were included in the study. Seven had positive skin-prick tests (the AEC group) and seven had negative skin-prick tests (the NAEC group). Eight asymptomatic subjects with negative skin-prick tests served as a control group. In conjunctival biopsies eosinophils were identified with monoclonal antibodies. Mast cells were identified by specific immunostaining and tryptase-positive granules were counted around them. The percentage of degranulated mast cells was used as a measure of cell activation. Eosinophil and goblet cell numbers were counted, epithelial thickness was measured, and the symptoms were characterized and graded. Results:, The numbers of eosinophils in biopsies were higher in patients with AEC than in healthy controls (p = 0.010). The proportion of activated mast cells tended to be higher in AEC patients (65%) than in NAEC patients (48%) or control subjects (40%). Patients with AEC had more goblet cells than control subjects (p = 0.049) and their epithelial layer was thicker (p = 0.054). Patients with AEC had more severe symptoms than control subjects (p = 0.0005), whereas the symptoms of NAEC patients did not differ statistically from those of controls (p = 0.065). Conclusions:, Patients with NAEC were characterized by mild eosinophilic inflammation and only minor structural conjunctival changes. The condition seems to run a relatively mild but persistent clinical course. [source]

Inflammatory cell mapping of the respiratory tract in fatal asthma

CLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2005
S. De Magalhães Simões
Summary Background The site and distribution of inflammation in the airways of asthmatic patients has been largely investigated. Inflammatory cells are distributed in both large and small airways in asthma. It has been demonstrated that distal lung inflammation in asthma may significantly contribute to the pathophysiology of the disease. The upper airways have also been implicated in the overall asthmatic inflammation. Although it is now accepted that lung inflammation is not restricted to the intrapulmonary airways in asthma, little is known about cell distribution in the other lung compartments and their relation to the intrapulmonary airways. Objective We aimed to map the inflammatory process in fatal asthma (FA), from the upper airways to the lung parenchyma. Methods Eosinophil, neutrophil, mast cell and lymphocyte content were determined in nasal mucosa, the trachea, intrapulmonary airways and parenchyma (peribronchiolar and distal) of 20 patients with FA and 10 controls. Results Eosinophil content was higher in all studied areas in FA compared with controls (P<0.02). Mast cell content was higher in the outer area of larger airways, small membranous bronchioles and in peribronchiolar parenchyma of FA compared with controls (P<0.04). CD3+, CD4+and CD20+cells showed increased content in FA intrapulmonary airways compared with controls (P<0.05). There was a positive correlation between CD4+cell content in nasal mucosa and larger airways in asthmatics. Increased neutrophil content was observed only in peribronchiolar parenchyma of FA (P=0.028). Conclusion Eosinophils present a widespread distribution within the respiratory tract in FA, from the nasal mucosa to the distal lung. The outer wall of small membranous bronchioles is the main site of inflammatory changes in FA. There is a localized distribution of alveolar inflammation at the peribronchiolar region for mast cells and neutrophils. Our findings provide further evidence of the importance of the lung periphery in the pathophysiology of FA. [source]

Eosinophil,epithelial cell interactions: an important facet of asthmatic inflammation

CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2002
Darren W. Sexton
No abstract is available for this article. [source]

Eosinophil,epithelial cell interactions: a special relationship?

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2001
Garry M. Walsh
[source]

CCR3-active chemokines influence eosinophil adhesion to endothelial cells under static and flow conditions

CLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2007
H. Tachimoto
Summary We recently demonstrated that CCR3-active chemokines promote rapid detachment of eosinophils bound to vascular cell adhesion molecule-1 (VCAM-1) in vitro. Eosinophils adhered well to immobilized human recombinant VCAM-1 primarily via ,4,1 integrin. Eotaxin-2, a CCR3-specific chemokine, induced eosinophil de-adhesion from VCAM-1. In contrast, very few eosinophils spontaneously adhered to bovine serum albumin (BSA), and eosinophil adhesion to BSA was enhanced by eotaxin-2 over a similar nm range of concentrations. This enhancement of BSA adhesion was dependent on ,2 integrins. Eosinophil ,4,1 integrins can mediate rolling on VCAM-1 under physiological flow conditions. Although we observed a reduction of eosinophil accumulation on immobilized VCAM-1 in response to eotaxin-2 under physiological flow conditions, this reduction of adhesion was not observed when VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) were co-immobilized. Based on antibody-blocking studies, this appears to be caused by a chemokine-induced shift in integrin usage away from ,1 integrin-dominated interactions with VCAM-1 towards ,2 integrin-dominated interactions with ICAM-1. Our results confirm the important role of integrins and chemokines in selective eosinophil migration processes. CCR3-active chemokines may be necessary to facilitate de-adhesion from luminal VCAM-1 and to facilitate the process of diapedesis by shifting integrin usage in eosinophils away from ,1 integrin-dominated interactions with VCAM-1 towards ,2 integrin-dominated interactions with ICAM-1. The critical importance of integrins and chemokines in eosinophilic inflammation lends support for targeting these molecules with novel therapeutic agents. [source]

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

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2000
G. T. Furuta
Eosinophil infiltration occurs in a variety of allergic and inflammatory diseases. The release of preformed mediators from eosinophils may contribute to inflammatory responses. We investigated the ability of eosinophil-derived major basic protein and eosinophil-derived neurotoxin to stimulate production of IL-8 from intestinal myofibroblasts. Intestinal myofibroblasts (18-Co cells) were incubated with major basic protein, eosinophil-derived neurotoxin, or a synthetic analogue of major basic protein, poly- l -arginine. Immunoreactive IL-8 was measured by ELISA and IL-8 mRNA levels were analysed by Northern blot or reverse transcription-polymerase chain assay. Major basic protein induced IL-8 mRNA production and release of significant levels of IL-8 immunoreactive protein. By contrast, eosinophil-derived neurotoxin stimulated little IL-8 release. The induction of IL-8 mRNA by poly- l -arginine was significantly inhibited by actinomycin D. These findings demonstrate a novel interaction between eosinophils and intestinal fibroblasts that may be involved in the pathogenesis of diseases associated with tissue eosinophilia. [source]

A new paradigm of eosinophil granulocytes: neuroimmune interactions

EXPERIMENTAL DERMATOLOGY, Issue 9 2008
Ulrike Raap
Abstract:, Eosinophil granulocytes have long been regarded as potent effector cells with the potential to release an array of inflammatory mediators involved in cytotoxicity to helminths and tissue destruction in chronic inflammatory diseases such as asthma. However, it has become evident that eosinophils are also involved in regulatory mechanisms modulating local tissue immune responses. Eosinophils take part in remodelling and repair mechanisms and contribute to the localized innate and acquired immune response as well as systemic adaptive immunity. In addition, eosinophils are involved in neuroimmune interactions modulating the functional activity of peripheral nerves. Neuromediators can also modulate the functional activity of eosinophils, revealing bidirectional interactions between the two cell types. Eosinophils are tissue-resident cells and have been found in close vicinity of peripheral nerves. This review describes neuroimmune interactions between eosinophil granulocytes and peripheral nerves and highlights why eosinophils are important in allergic diseases such as asthma. [source]

Blood cell profile of six Mediterranean mariculture fish species

JOURNAL OF APPLIED ICHTHYOLOGY, Issue 1 2007
M. Pavlidis
Summary The haematological profile and a description of the cell types from the peripheral blood of six Mediterranean fish species are presented. The highest haematocrit value was recorded in the saupe, Sarpa salpa (P < 0.001), the only herbivorous species, and which also lacked monocyte cells. Eosinophils were absent from the blood of the European sea bass Dicentrarchus labrax. White sea bream, Diplodus sargus and gilthead sea bream, Sparus aurata had statistically significantly high numbers of neutrophils and low numbers of lymphocytes (P < 0.001). The numbers of different leucocyte cell types were not influenced by sex or maturity stage in any species, although some variation in the maximum diameter of the cells was observed. [source]

Indications of ,atopic bowel' in patients with self-reported food hypersensitivity

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2010
K. LILLESTØL
Aliment Pharmacol Ther,31, 1112,1122 Summary Background, An association between atopic disease and gastrointestinal complaints has been suggested. Aim, To explore the association between atopic disease, gastrointestinal symptoms, and possible gastrointestinal manifestations of atopic disease in patients with self-reported food hypersensitivity. Methods, Symptoms, skin prick tests, serum markers of allergy and intestinal permeability were recorded in 71 adult patients. Eosinophils, tryptase- and IgE-positive cells were counted in duodenal biopsies. Results, Sixty-six (93%) patients had irritable bowel syndrome (IBS) and 43 (61%) had atopic disease, predominantly rhinoconjunctivitis. All 43 were sensitized to inhalant allergens, 29 (41%) to food allergens, but food challenges were negative. Serum total IgE and duodenal IgE-positive cell counts were significantly correlated (P < 0.0001) and both were significantly higher in atopic than in non-atopic patients (P < 0.0001 and P = 0.003 respectively). IgE-positive cells appeared to be ,armed' mast cells. Intestinal permeability was significantly elevated in atopic compared with non-atopic patients (P = 0.02). Gastrointestinal symptoms and numbers of tryptase-positive mast cells and eosinophils did not differ between groups. Conclusions, Patients with self-reported food hypersensitivity had a high prevalence of IBS and atopic disease. Atopic patients had increased intestinal permeability and density of IgE-bearing cells compared with non-atopic patients, but gastrointestinal symptoms did not differ between groups. [source]

Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009
M. M. WALKER
Summary Background, Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional disorders without defined pathology. Mast cells and eosinophils interact with T lymphocytes and may alter enteric nerve and smooth muscle function. Aim, To examine mast cell, eosinophil and intraepithelial lymphocyte populations in duodenal biopsies of subjects with IBS and FD. Methods, A random sample of an adult Swedish population (n = 1001; mean age 54 years; 51% female) underwent upper endoscopy and biopsy; 51 cases with FD and 41 cases with IBS were compared with 48 randomly selected controls. Eosinophils were identified by light microscopy; mast cells by immunocytochemistry (CD117). Intraepithelial lymphocytes were counted per 100 enterocytes. Cell counts were quantified by counting the number per high power field (HPF) in 5HPFs in the bulb (D1) and second part of duodenum (D2), summed over 5HPFs at each site. Results, Cases and controls showed similar demographics. Compared to controls, IELs in IBS-constipation were significantly increased (P = 0.005). Mast cells were significantly increased in IBS in D2 (P < 0.001), while eosinophils were significantly increased in FD in D1 and D2 (P < 0.001). Conclusion, Duodenal mast cell hyperplasia is linked to IBS and eosinophilia to FD, and duodenal biopsy may identify subsets of these disorders. [source]

CC Chemokine Receptor 4 (CCR4) in human allergen-induced late nasal responses

ALLERGY, Issue 9 2010
G. Banfield
To cite this article: Banfield G, Watanabe H, Scadding G, Jacobson MR, Till SJ, Hall DA, Robinson DS, Lloyd CM, Nouri-Aria KT, Durham SR. CC Chemokine Receptor 4 (CCR4) in human allergen-induced late nasal responses. Allergy 2010; 65: 1126,1133. Abstract Background:, CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4-mediated inflammation may be important in the pathology of allergic rhinitis. Disruption of CCR4 , ligand interaction may abrogate allergen-induced inflammation. Methods:, Sixteen allergic rhinitics and six nonatopic individuals underwent both allergen and control (diluent) nasal challenges. Symptom scores and peak nasal inspiratory flow were recorded. Nasal biopsies were taken at 8 h post challenge. Sections were immunostained and examined by light or dual immunofluorescence microscopy for eosinophils, T-lymphocytes, CCR4+CD3+ and CXCR3+CD3+ cells and examined by in situ hybridization for CCR4, IL-4 and IFN-, mRNA+ cells. Peripheral blood mononuclear cells were obtained from peripheral blood of nine normal donors and the CCR4+CD4+ cells assessed for actin polymerization in response to the CCR4 ligand macrophage-derived chemokine (MDC/CCL22) and the influence of a CCR4 antagonist tested. Results:, Allergic rhinitics had increased early and late phase symptoms after allergen challenge compared to diluent; nonatopics did not respond to either challenge. Eosinophils, but not total numbers of CD3+ T cells, were increased in rhinitics following allergen challenge. In rhinitics, there was an increase in CCR4+CD3+ protein-positive cells relative to CXCR3+CD3+ cells; CCR4 mRNA+ cells were increased and IL-4 increased to a greater extent than IFN-,. CCR4+CD4+ T cells responded to MDC in vitro, and this response was inhibited by the selective CCR4 antagonist. Conclusion:, Lymphocyte CCR4 expression is closely associated with induction of human allergen-induced late nasal responses. Blocking CCR4-ligand interaction may provide a novel therapeutic approach in allergic disease. [source]

Inflammatory profiles in nasal mucosa of patients with persistent vs intermittent allergic rhinitis

ALLERGY, Issue 9 2010
F. Liu
To cite this article: Liu F, Zhang J, Liu Y, Zhang N, Holtappels G, Lin P, Liu S, Bachert C. Inflammatory profiles in nasal mucosa of patients with persistent vs intermittent allergic rhinitis. Allergy 2010; 65: 1149,1157. Abstract Background:, To date there is little information on the inflammatory profiles of patients suffering from persistent (PER) and intermittent allergic rhinitis (IAR). Also, it is not clear whether differences exist in eosinophilic inflammation and/or T-helper cell sub-populations and their markers. The aim of this study was to primarily evaluate the inflammatory profiles of patients with moderate/severe PER and IAR. Methods:, Inferior nasal turbinate tissue was obtained from 12 PER, 12 IAR and 12 nonallergic nonrhinitic (control) patients, and symptoms (visual analogue scales, VAS) and impairment of life was monitored. All tissues were assessed for eosinophil and mast cell numbers by immunohistochemistry; IL-5, ECP and IgE concentrations by immunoassay; mRNA for transcription factors GATA-3, T-bet, FOXP3 and RORc by quantitative real-time polymerase chain reaction; and IgE-induced release of LTC4/D4/E4 and PGD2in vitro. Results:, Eosinophils and mast cells were significantly increased in patients with PER and patients with IAR compared to control subjects; by patients with PER demonstrating even significantly greater increase of both cell types than patients with IAR. Similarly, ECP IL-5, GATA-3 mRNA expression and IgE-induced release of LTC4/D4/E4 and PGD2 from mast cells were significantly increased in patients with PER compared to patients with IAR. In contrast, the expression of T-bet, FOXP3 or RORc mRNA was not significantly different in the PER, IAR or control patients. Conclusion:, The findings from the present study suggest that PER is characterized by a significantly greater eosinophilic and predominantly Th2 cell-mediated nasal inflammatory profile compared to IAR. [source]

Markers of eosinophilic and neutrophilic inflammation in bronchoalveolar lavage of asthmatic and atopic children

ALLERGY, Issue 8 2010
D. Snijders
To cite this article: Snijders D, Agostini S, Bertuola F, Panizzolo C, Baraldo S, Turato G, Faggian D, Plebani M, Saetta M, Barbato A. Markers of eosinophilic and neutrophilic inflammation in bronchoalveolar lavage of asthmatic and atopic children. Allergy 2010; 65: 978,985. Abstract Background:, Recent studies performing fiberoptic bronchoscopy in children have improved our understanding of asthma pathophysiology. Eosinophilic, but also neutrophilic, inflammation has been described in asthma, but the relationship with atopy was incompletely investigated. The aim of this study is to examine inflammatory cells and mediators in children with asthma compared to the appropriate controls, i.e. atopic children without asthma and children with no atopy or asthma. Moreover, asthmatic children were analysed separately based on the presence of atopy and stratified by age. Methods:, We recruited 191 children undergoing fiberoptic bronchoscopy for appropriate indications: 91 asthmatics (aged 1.4,17 years), 44 atopics without asthma (1.6,17.8 years) and 56 nonasthmatic nonatopic controls (1.4,14 years). In bronchoalveolar lavage, total and differential cell counts and inflammatory mediators, including ECP, eotaxin, IL-8 and TNF,, were analysed. Results:, Eosinophils and ECP levels were increased in asthmatic children when compared to controls (P = 0.002 and P = 0.01, respectively), but also atopic children without asthma had increased ECP levels compared to controls (P = 0.0001). Among asthmatic children, eosinophils and ECP levels were not different between atopic and nonatopic individuals. Neither neutrophils nor the related mediators (IL-8 and TNF,) differed significantly in the three groups. This pattern of inflammation was observed in both preschool and school-aged asthmatic children. Conclusions:, This study suggests that markers of eosinophilic, but not neutrophilic inflammation, are increased in asthmatic children and also in atopic children without asthma. Of interest, in asthmatic children, the activation of the eosinophilic response is not solely because of the presence of atopy. [source]

IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg,Strauss syndrome

ALLERGY, Issue 7 2010
A. Bossios
To cite this article: Bossios A, Sjöstrand M, Dahlborn A-K, Samitas K, Malmhäll C, Gaga M, Lötvall J. IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg,Strauss syndrome. Allergy 2010; 65: 831,839. Abstract Background:, Eosinophils develop from hematopoietic CD34+ progenitor cells in the bone marrow (BM) under the influence of Interleukin-5 (IL-5). The primary source of IL-5 is T-lymphocytes, although other sources may exist. The aims of this study were to determine whether CD34+ cells from human peripheral blood (PB) and BM have the capacity to produce IL-5 when stimulated in vitro, and secondly, whether an elevated number of IL-5-producing CD34+ cells can be found in situ in ongoing eosinophilic disease. Methods:, CD34+ cells from PB and BM were stimulated in vitro, and IL-5 production and release was assessed by ELISA, ELISPOT, flow cytometry and immunocytochemistry. Blood and BM from a patient with Churg,Strauss syndrome were analyzed by flow cytometry for CD34+/IL-5+ cells, and immunohistochemical staining of CD34+/IL-5+ cells in bronchial biopsies from an asthmatic patient was performed. Results:, Both PB and BM CD34+ cells can produce and release IL-5 when stimulated in vitro. In the Churg,Strauss patient, IL-5-producing CD34+ cells were found in PB and BM. Oral glucocorticoid treatment markedly decreased the number of IL-5-positive CD34 cells in the BM. CD34+/IL-5+ cells were present in a patient with asthma. Conclusion:, CD34+ cells in blood and BM are capable of producing IL-5 both in vitro and in vivo in humans, arguing that these cells may have the capacity to contribute to eosinophilic inflammation. Consequently, targeting CD34+ progenitor cells that produce and release IL-5 may be effective in reducing the mobilization of eosinophil lineage-committed cells in eosinophilic-driven diseases. [source]

Osteopontin is expressed and functional in human eosinophils

ALLERGY, Issue 2 2010
I. Puxeddu
To cite this article: Puxeddu I, Berkman N, Ribatti D, Bader R, Haitchi HM, Davies DE, Howarth PH, Levi-Schaffer F. Osteopontin is expressed and functional in human eosinophils. Allergy 2010; 65: 168,174. Abstract Background:, Eosinophils are critically involved in allergic inflammation and tissue remodeling. Osteopontin (OPN) is a glycoprotein molecule which exhibits pro-fibrogenic and pro-angiogenic properties and has recently also been implicated in allergic diseases. In this study, we investigated the expression and function of OPN in human eosinophils. Methods:, Osteopontin mRNA (RT-PCR) and protein (immunofluorescence) expression in peripheral blood eosinophils from atopic human subjects were evaluated. Soluble OPN release was determined in resting and activated eosinophils. The contribution of OPN to eosinophil-induced angiogenesis was determined using the chick embryo chorio- allantoic membrane (CAM) assay and OPN-induced eosinophil chemotaxis was determined (ChemoTx System microplate wells). Finally, OPN expression in bronchoalveolar lavage (BAL) fluids from mild asthmatic and normal control subjects was determined. Results:, Osteopontin is expressed in human eosinophils and is increased following GM-CSF and IL-5 activation. Eosinophil-derived OPN contributes to eosinophil-induced angiogenesis. Recombinant OPN promotes eosinophil chemotaxis in vitro and this effect is mediated by ,4,1 integrin binding. Soluble OPN is increased in the bronchoalveolar lavage fluid from mild asthmatic subjects and correlates with eosinophil counts. Conclusions:, We therefore conclude that OPN is likely to contribute to the process of angiogenesis observed in the airways in asthma. [source]

Plasma levels and skin-eosinophil-expression of vascular endothelial growth factor in patients with chronic urticaria

ALLERGY, Issue 11 2009
A. Tedeschi
Background:, Although chronic urticaria (CU) is often regarded as autoimmune in nature, only less than 50% of sera from CU patients contain histamine-releasing autoantibodies. This suggests that other factors may contribute to its pathogenesis. We evaluated the possible involvement of vascular endothelial growth factor (VEGF), one of the major mediators of vascular permeability, in CU. Methods:, Eighty consecutive adult patients with CU and 53 healthy subjects were studied. VEGF and prothrombin fragment F1+2 were measured by enzyme immunoassays. Autologous plasma skin test (APST) was performed in CU patients and, in six of them, skin biopsy specimens were taken from wheals to evaluate the immunohistochemical expression of VEGF and eosinophil cationic protein (ECP). Results:, Plasma VEGF concentrations were higher in CU patients (8.00 ± 0.90 pmol/l) than in controls (0.54 ± 0.08 pmol/l) (P = 0.0001) and tended to parallel both the severity of CU and to correlate with F1+2 levels. APST was positive in 85.1% of patients. VEGF concentration was significantly higher in APST-positive than in APST-negative patients (P = 0.0003). Immunohistochemically, all specimens from patients with CU showed a strong expression of VEGF (P = 0.002) that colocalized with ECP, a classic eosinophil marker. Conclusions:, VEGF plasma levels are elevated in CU and parallel the disease severity. This supports a possible role of this molecule in CU pathophysiology. Eosinophils are the main cellular source of VEGF in CU lesional skin. [source]

Thioredoxin reduces C-C chemokine-induced chemotaxis of human eosinophils

ALLERGY, Issue 8 2009
N. Kobayashi
Background:, Human thioredoxin (TRX) is one of redox-active proteins that regulate reactive oxidative metabolisms. In recent study, we found that serum levels of TRX were elevated in asthmatic patients with exacerbation; however, few details are known about the physiological role of TRX in allergic inflammation, involving eosinophil infiltration. Objective:, In the present study, we examined whether TRX modulated C-C chemokine-induced chemotaxis of human eosinophils. Methods:, Eosinophils were isolated from subjects with mild eosinophilia by modified CD16 negative selection. After incubation with or without recombinant TRX, chemotaxis of human eosinophils was measured using Boyden chamber. Results:, Preincubation with TRX suppressed eotaxin- and regulated on activation, normal T-cell expressed and secreted (RANTES)-induced chemotaxis of eosinophils. Although, TRX had no effect on the expression of C-C chemokine receptor 3, which is a receptor of eotaxin and RANTES, we demonstrated that the activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinases, which play an important role in eosinophil migration, was attenuated by the treatment with TRX. Conclusion:, Our results suggest that the elicited TRX is beneficial to reduce allergic inflammation through negative regulation of eosinophil functions and has potential in the treatment of allergic diseases, such as asthma. [source]

Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment

ALLERGY, Issue 1 2009
E. L. J. Van Rensen
Background:, Anti-IgE, omalizumab, inhibits the allergen response in patients with asthma. This has not been directly related to changes in inflammatory conditions. We hypothesized that anti-IgE exerts its effects by reducing airway inflammation. To that end, the effect of anti-IgE on allergen-induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a randomized, double-blind, placebo-controlled study. Methods:, Allergen challenge followed by a bronchoscopy at 24 h was performed at baseline and after 12 weeks of treatment with anti-IgE or placebo. Provocative concentration that causes a 20% fall in forced expiratory volume in 1 s (PC20) methacholine and induced sputum was performed at baseline, 8 and 12 weeks of treatment. Changes in the early and late responses to allergen, PC20, inflammatory cells in biopsies and sputum were assessed. Results:, Both the early and late asthmatic responses were suppressed to 15.3% and 4.7% following anti-IgE treatment as compared with placebo (P < 0.002). This was paralleled by a decrease in eosinophil counts in sputum (4,0.5%) and postallergen biopsies (15,2 cells/0.1 mm2) (P < 0.03). Furthermore, biopsy IgE+ cells were significantly reduced between both the groups, whereas high-affinity IgE receptor and CD4+ cells were decreased within the anti-IgE group. There were no significant differences for PC20 methacholine. Conclusion:, The response to inhaled allergen in asthma is diminished by anti-IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE-bearing cells postallergen without changing PC20 methacholine. This suggests that the benefits of anti-IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE-bearing cells. [source]

Eosinophils and atopic dermatitis

ALLERGY, Issue 6 2004
D. Simon
In spite of the progress regarding the description of immunological phenomena associated with atopic dermatitis (AD), the pathogenesis of this disease still remains unclear. The presence of eosinophils in the inflammatory infiltrate of AD has long been established. Eosinophil numbers as well as eosinophil granule protein levels in peripheral blood are elevated in most AD patients and appear to correlate with disease activity. Moreover, eosinophil granule proteins, which possess cytotoxic activity, are deposited in the skin lesions. These observations indicate a role of eosinophils in the pathogenesis of AD. Furthermore, AD is associated with increased production of T helper 2 cytokines including interleukin (IL)-5, which specifically acts on eosinophils, resulting in accelerated eosinophilopoiesis, chemotaxis, cell activation, and delayed apoptosis. Therefore, IL-5 is an interesting target for experimental therapy in this inflammatory disorder of the skin. Such studies might result in new insights into the pathogenetic role of eosinophils in AD. [source]

Eosinophils: ,new' roles for ,old' cells

ALLERGY, Issue 3 2004
A. Munitz
Prominent blood and tissue eosinophilia is manifested in a number of inflammatory states, particularly in allergic diseases. Eosinophils are a source of numerous cytokines and growth factors, thus in principle they can display both pro-inflammatory and anti-inflammatory activities as well as immunoregulatory ones. In this review, we will discuss the cross-talk between eosinophils and other cell types that they come in contact with in the inflammatory milieu, such as mast cells, fibroblasts and endothelial cells. ,New' roles for eosinophils in cancer and novel activatory signals will also be described. [source]

Mucosal mast cells mediate motor response induced by chronic oral exposure to ovalbumin in the rat gastrointestinal tract

NEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2010
E. Traver
Abstract, We previously demonstrated that oral chronic exposure to ovalbumin (OVA) causes intestinal hypermotility in Sprague-Dawley rats. In this study, the objective was to determine the mechanism of action of OVA and the role of mucosal mast cells in the regulation of motor activity in this model. Rats were orally exposed to OVA during 6 weeks. Intestinal mucosal mast cells (IMMCs) were counted and rat mast cell protease II (RMCPII) measured in duodenum, jejunum, ileum and colon. Anti-OVA IgE, IgG, and IL-4 were measured in serum. Eosinophils and IgE+ cells were counted in jejunum. In an additional study rats were treated with the mast cell stabilizer ketotifen and mast cell number, RMCPII concentration and motor activity in vitro were evaluated. OVA exposed rats showed an increase in mucosal mast cell number and in RMCPII content in small intestine and colon. However, variables of a Th2 type response were not affected by exposure to OVA: (i) neither OVA specific IgE nor IgG were found; (ii) IL-4 did not increase and, (iii) the number of eosinophils and IgE+ cells was identical in the exposed and unexposed groups. These results brought us to hypothesize a possible non-Ig-mediated action of OVA on mast cells. Ketotifen significantly diminished the response to OVA: Ketotifen reduced the number of mast cells and the RMCPII content and blocked increased intestinal contractility. In addition ketotifen modified motor response in both OVA exposed and unexposed animals giving evidence of the importance of mast cells in intestine motor activity driving. [source]

Eosinophil cationic protein damages protoscoleces in vitro and is present in the hydatid cyst

PARASITE IMMUNOLOGY, Issue 8 2006
A. L. RAMOS
SUMMARY Eosinophils are locally recruited during the establishment and chronic phases of cystic hydatidosis. This study provides evidence that eosinophil cationic protein (ECP), one of the major components of eosinophil granules, can damage Echinococcus granulosus protoscoleces (PSC). The toxicity of ECP was investigated in vitro by following parasite viability in the presence of this protein. ECP was found to damage PSC at micromolar concentrations; the effect was blocked by specific antibodies and heparin, and was more severe than the one caused by similar concentrations of RNase A, suggesting that the cationic nature of ECP, and not its ribonuclease activity, is involved in toxicity. This observation may highlight the capacity of eosinophils to control secondary hydatidosis, derived from PSC leakage from a primary cyst. To further assess the relevance of the previous result during infection, the presence of eosinophil proteins was investigated in human hydatid cysts. ECP was found to be strongly associated with the laminated layer of the cyst wall, and present at micromolar concentrations in the hydatid fluid. Overall, these results demonstrate that eosinophils degranulate in vivo at the host,parasite interface, and that the released ECP reaches concentrations that could be harmful for the parasite. [source]

Comparison of atopic and nonatopic children with chronic cough: Bronchoalveolar lavage cell profile,

PEDIATRIC PULMONOLOGY, Issue 10 2007
Flavia de A Ferreira MD
Abstract Chronic cough is a common complaint in children and its relationship with asthma is controversial. The aim of the present study was to determine the pattern of airway inflammation in atopic and nonatopic children with chronic cough, and to investigate whether atopy is a predictive factor for eosinophilic inflammation in cough. Bronchoalveolar lavage (BAL; three aliquots of 1 ml/kg saline) was performed in the right middle lobe of 24 (11 atopic and 13 nonatopic) children with persistent cough (8 females, 16 males), mean age 4.7 years (range: 1,11). Atopy was defined as an elevated total serum IgE or a positive RAST test. Both atopic and nonatopic children with persistent cough had an increase in total cells/ml in BAL (atopic: median 39,×,104, range: 20,123; nonatopic: median 22,×,104, range: 17,132) compared to nonatopic controls (median 11,×,104, range 9,30). The increases were mainly in neutrophils (atopic: median 17%, range 2.5,88.5%; nonatopic: median 6%, range 1.0,55.0%) compared to controls (median 1.55%, range 0.5,7.0%; atopics vs. controls, P,<,0.005). There were no significant increases in eosinophils, lymphocytes, epithelial cells, or mast cells. Eosinophils were elevated in only 5/11 atopic and none of the nonatopic children. The increased percentage of neutrophils in the BAL fluid of atopic and nonatopic children with persistent cough could be due to an underlying inflammatory process driving the cough, or even conceivably, due to the effect of coughing itself. In this highly selected series, the absence of eosinophilic inflammation in the majority suggests that most would be predicted not to respond to inhaled corticosteroid therapy. This study underscores the need to be cautious about treating coughing children with inhaled corticosteroids, even in the context of a tertiary referral practice. Pediatr Pulmonol. 2007;42:857,863. © 2007 Wiley-Liss, Inc. [source]

Apoptosis and Phagocytosis of Tissue-Dwelling Eosinophils in Sinonasal Polyps,

THE LARYNGOSCOPE, Issue 1 2000
Åke Davidsson MD
Abstract Objective: Sinonasal polyps contain numerous tissue-dwelling eosinophils, but the mechanisms causing their accumulation, functional activities, and resolution are largely unknown. Study Design: Nasal polyp tissue from 14 patients was evaluated for cellular expression of CD95, CD68, and Annexin-V, for the degree of apoptosis, and for phagocytosis of eosinophils. Material and Methods: Histological sections were immunostained as single stains for CD95, CD68, and Annexin-V, and as an immunostaining for CD68 combined with a modified Vital New Red staining. The latter staining is specific for eosinophils. Other sections were stained by terminal d-UTP nick end labeling (TUNEL) assay and routinely stained for H&E. Evaluation of the amount of stained cells was performed by counting the average number in 10 randomly chosen high-power fields. The TUNEL positivity was in all cases confirmed with apoptotic morphology. Results: The inflammatory infiltrate consisted of numerous eosinophils but also a considerable amount of lymphocytes, mast cells, and macrophage-like CD68+ cells. CD95 was frequently expressed on eosinophils, on numerous other inflammatory cells, and also on morphologically apoptotic cells. Annexin-V-positive eosinophils were not as frequent as CD95+ cells, but numerous Annexin-V-positive eosinophils were found. CD68+ cells approximately equalled the number of eosinophils. The number of cells phagocytosing eosinophils varied between polyps. Apoptosis of eosinophils (as evaluated by TUNEL combined with apoptotic morphology) was a common finding in six of the polyps. Conclusions: Previous in vitro and ex vivo findings of CD95 on eosinophils are now supported by demonstration of CD95 on eosinophils in this in vivo study. This investigation revealed a switch of the membrane-bound phosphatidylserine of apoptotic cells, which is a novel observation. The study has demonstrated apoptosis of tissue-dwelling eosinophils, and that CD68+ macrophage-like cells phagocytose eosinophils within the sinonasal polyps. [source]

Ultrastructural Characteristics of Blood Cells of Juvenile Loggerhead Sea Turtles (Caretta caretta)

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2007
A. B. Casal
Summary Ultrastructural characteristics of erythrocytes, heterophils, eosinophils, lymphocytes, monocytes and thrombocytes of the loggerhead sea turtle (Caretta caretta) were evaluated, using blood samples from 15 healthy juvenile animals. Except for the eosinophils, the rest of the white blood cells from loggerhead turtles had similar ultrastructural characteristics compared with blood cells from other sea turtle species. Eosinophils from loggerhead turtles were homogeneous in size, and no crystalline structures were observed within the granules. This paper provides an ultrastructural characterization of blood cells of loggerhead sea turtles, as a reference for future haematological studies of this species. [source]

Phagocytosis of heat-killed Staphylococcus aureus by eosinophils: comparison with neutrophils

APMIS, Issue 2 2009
YASUKO HATANO
Eosinophils are characterized by several functional properties, such as chemotaxis, adhesion, superoxide anion production, and degranulation. In this article, we have studied the role of bacterial ingestion by eosinophils in comparison with that by neutrophils. Eosinophils and neutrophils were purified by using the Percoll gradient method followed by selection with CD16-coated immunomagnetic beads and centrifugation through a Ficoll-Hypaque gradient combined with dextran sedimentation, respectively. Both cells were preincubated with anti-Fc,RIIa mAb (CD32 mAb), anti-Fc,RIIIb mAb (CD16 mAb), anti-CR3 (CD11b mAb), or anti-CR1 (CD35 mAb) before being examined for phagocytosis of opsonized heat-killed Staphylococcus aureus (S. aureus). Phagocytosis and production of hydrogen peroxide were simultaneously measured by flow cytometry using S. aureus labeled with propidium iodide and stained with 2,,7,-dichlorofluorescein diacetate. Eosinophils showed significantly lower activity than neutrophils in both phagocytosis and hydrogen peroxide production. Phagocytosis by both cells was decreased by heat-inactivated serum. Phagocytosis by neutrophils was significantly inhibited by CD16 mAb and CD32 mAb, whereas that by eosinophils was only inhibited by CD35 mAb. Whereas the mechanism of phagocytosis by neutrophils was mediated by CD16 and CD32, that of eosinophils was modulated by complement receptor 1 (CD35). [source]

Cytokines, Eosinophils, Lymphocytes, and ICAM

ACTA OPHTHALMOLOGICA, Issue 2000
Neal P. Barney
No abstract is available for this article. [source]

Inhibitory effects of N -acetylcysteine on the functional responses of human eosinophils in vitro

CLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2007
M. Martinez-Losa
Summary Background Oxidative stress appears to be relevant in the pathogenesis of inflammation in allergic diseases like bronchial asthma. Eosinophils are oxidant-sensitive cells considered as key effectors in allergic inflammation. Objective The aim of this work was to study the effects of the clinically used antioxidant N -acetyl- l -cysteine (NAC) on the functional responses of human-isolated eosinophils. Methods Human eosinophils were purified from the blood of healthy donors by a magnetic bead separation system. The effects of NAC were investigated on the generation of reactive oxygen species (chemiluminescence and flow cytometry), Ca2+ signal (fluorimetry), intracellular glutathione (GSH; flow cytometry), p47phox,p67phox translocation (Western blot) and eosinophil cationic protein (ECP) release (radioimmunoassay). Results NAC (0.1,1 mm) inhibited the extracellular generation of oxygen species induced by N -formyl- l -methionyl- l -leucyl- l -phenylalanine (fMLP) and eotaxin (in the presence of IL-5) with ,logIC50 values of 3.61±0.03 and 3.36±0.09, respectively. Also, the intracellular generation of hydrogen peroxide was virtually abolished by NAC (0.5,1 mm). NAC (1 mm) did not alter the fMLP-induced Ca2+ signal but augmented the eosinophil content of reduced GSH and inhibited p47phox,p67phox translocation. NAC inhibited the release of ECP (,90% inhibition at 1 mm) from fMLP-activated eosinophils. Conclusion Inhibition by NAC of human eosinophil functions in vitro is potentially useful in the treatment of allergic inflammation. [source]

Increased expression of collagen receptors: ,1,1 and ,2,1 integrins on blood eosinophils in bronchial asthma

CLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2006
S. Bazan-Socha
Summary Background Eosinophils are one of the major effector cells in bronchial asthma. Their infiltration of airways correlates with the asthma severity. Recruitment and activation of eosinophils are partially mediated by integrins ,4,1 and ,4,7. Collagens type I and IV constitute important components of extracellular matrix and vascular basement membrane, respectively. Therefore, collagen-binding integrins (,1,1 and ,2,1) may also play a role in eosinophil lung infiltration. Objective To evaluate the possible presence of ,1,1 and ,2,1 integrins on peripheral blood eosinophils from asthmatic subjects. Methods Collagen receptors were studied on eosinophils separated by immunomagnetic CD16-negative method from healthy donors (n=13) and patients with moderate persistent atopic bronchial asthma (n=15). Surface receptor identification was performed by flow cytometry and cell adhesion assay. Results Eosinophils isolated from the patients showed increased expression of both ,1,1 and ,2,1 integrins as compared with healthy controls. Moreover, adhesive function of eosinophils to collagen type IV was inhibited by snake venom disintegrins: viperistatin and obtustatin. These disintegrins contain KTS active motif and are specific inhibitors of ,1,1 integrin. Conclusion We demonstrated for the first time that collagen receptors: ,1,1 and ,2,1 integrins are overexpressed on the surface of peripheral blood eosinophils of asthmatic subjects. Further studies may reveal potential application of KTS-disintegrins or their structural analogs for therapy of bronchial asthma. [source]