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Biomedical subjects

M Capron

Publications and source records attributed to M Capron.

At least 37 records · Page 2Linked to original sources
PubMed1996

IgE autoantibodies directed against the major bullous pemphigoid antigen in patients with a severe form of pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized in part by circulating and tissue-bound IgG autoantibodies directed against the basement membrane zone. In addition, most of the patients with BP have increased serum IgE levels which seem to be correlated with the disease activity, whereas the presence of circulating anti-basement membrane zone IgE Abs has been reported in some patients. To elucidate whether IgE-dependent mechanisms play a role in the physiopathology of BP, we looked for the presence of IgE Abs specifically directed against the major BP Ag (BPAg1) in sera of BP patients at the onset and after remission of the disease. A radioimmunoassay and a 55-kDa recombinant protein (rBP55) obtained from a cDNA sequence, encoding the C-terminal region of the BPAg1 and containing the BPAg1 immunodominant epitopes, were used. Anti-rBP55 IgE Abs were found in 12 of the 19 sera tested. When the patients were divided into two groups according to the disease severity, anti-rBP55 IgE Abs were found only in patients with a severe form of the disease. Cytophilic IgE was detected on approximately 20% of peripheral blood eosinophils purified from BP patients. Immunohistochemistry studies suggested that some of the IgE-bearing cells in the lesional skin of BP patients are eosinophils. Immunostaining experiments revealed the existence of FcepsilonRI on both peripheral blood and tissue eosinophils. Taken together, these results suggest that IgE-dependent mechanisms could participate in the constitution of the lesions in BP.

Antibody Specificity↗
PubMed1996

Eosinophils express a functional receptor for interferon alpha: inhibitory role of interferon alpha on the release of mediators.

Recent reports describe the beneficial use of alpha interferon (IFNalpha) for the treatment of idiopathic hypereosinophilic syndrome (HES) unresponsive to conventional therapy. A clinical improvement associated with a rapid decrease of peripheral blood eosinophilia suggested possible direct effects of IFNalpha on eosinophils through the presence of IFNalpha receptors (IFNalphaR). Reverse transcriptase-polymerase chain reaction (RT-PCR) and cytochemistry were used respectively to detect the presence and define the distribution of IFNalphaR on enriched eosinophil preparations purified from blood cells. IFNalphaR was found on eosinophils collected from patients with various eosinophilic disorders. In addition, IFNalpha inhibited the release of eosinophil granule proteins such as eosinophil cationic protein (ECP), neurotoxin (EDN, or interleukin-5 (IL-5). Moreover, antiparasite cytotoxicity was also strongly reduced in a dose-dependent manner by IFNalpha. These results provide the first evidence that human eosinophils express a functional receptor for IFNalpha and represent a potential basis for the beneficial effects of IFNalpha in patients with hypereosinophilic syndromes.

Animals↗
PubMed1996

Eosinophils in allergic reactions.

Mainly located in the skin or mucosa of patients with allergic diseases, eosinophils contribute directly to tissue damage and chronic inflammation. The past year has seen significant advances in the study of the factors involved in the specific tissue recruitment of eosinophils, including chemoattractants and their receptors. New data have been obtained on the synthesis by eosinophils of various cytokines mostly released by immune complexes.

Animals↗
PubMed1996

Effect of intrajejunal elemental diet perfusion on local secretion of soluble CD4 and CD8.

The effects of nutrients on the mucosal immune system are poorly understood. The aim of this work was to study the cellular mucosal immune response to intrajejunal perfusion of an elemental diet (ED) or a control (C) electrolyte solution by measuring jejunal secretion of soluble CD4 (sCD4) and sCD8. sCD4 and sCD8 are markers of helper/inducer and suppressor/cytotoxic regulatory functions of T cells, respectively. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with C for 80 min and then with ED containing 21.3 g/l of free amino acids and 104.2 g/l of oligosaccharides for 100 min. Jejunal fluid and serum concentrations of sCD4 and sCD8 were measured and their jejunal outputs calculated. When compared with C perfusion, jejunal perfusion with the ED resulted in a significant increase of sCD8 but not sCD4 jejunal secretion rates. sCD8 jejunal values increased early after ED perfusion and stayed at roughly the same level during the perfusion. Serum concentrations of sCD4 and sCD8 were not modified during ED perfusion. These data support the hypothesis that ED suppresses the immunologic tone of the gut, which could explain its beneficial effect in the management of intestinal inflammatory disease.

Adult↗
PubMed1996

Interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 in eosinophilic gastroenteritis.

BACKGROUND & AIMS: Eosinophilic gastroenteritis (EG) is characterized by an eosinophilic infiltration of the gastrointestinal tract. The mechanism for the intestinal recruitment of eosinophils in EG remains unknown. Eosinophil recruitment and activation is induced by three main cytokines: interleukin (IL) 3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5. The aim of this study was to examine the immunoreactivity for IL-3, GM-CSF, and IL-5 within the duodenal and colonic mucosa of 10 patients with EG. METHODS: Endoscopic biopsy specimens were obtained from 10 patients with EG and 10 controls. IL-3, GM-CSF, and IL-5 was evaluated by immunohistochemistry. Electron microscopy combined with immunogold staining was used to identify the labeled cells and to localize these growth factors ultrastructurally. RESULTS: A significant increase in the number of eosinophils was found in both duodenal and colonic mucosa from all 10 patients with EG compared with controls. In the same tissue, immunohistochemistry detected IL-3, GM-CSF, and IL-5 in 9 of 10 patients with EG. The one exception had received treatment with steroids. These cytokines were not detected in the control group. Ultrastructurally, IL-3, GM-CSF, and IL-5 were localized in the granule matrix of eosinophils. CONCLUSIONS: The release of these cytokines with autocrine and/or paracrine activities by eosinophils may be involved in the persistence of intestinal eosinophil infiltration.

Adolescent↗
PubMed1996

Internalization of human lactoferrin by the Jurkat human lymphoblastic T-cell line.

Binding of either iron-saturated or iron-free lactoferrin to the Jurkat human lymphoblastic T-cell line was saturable with a dissociation constant Kd of 40 nM. The total number of binding sites was estimated to be approximately 300,000. Non-specific binding did not exceed 30% of the total binding. Removal of the 4 clustered arginine residues of lactoferrin at position 2 to 5, which are involved in the interactions with heparan sulfate, did not modify the binding parameters. Therefore, the high number of low affinity binding sites previously described as responsible for the interaction of lactoferrin with either hepatocytes, enterocytes or the U937 monocytic cell line, is not involved in the binding of lactoferrin to Jurkat cells. After binding at 4 degrees C, a shift to 37 degrees C causes cell to internalize lactoferrin, with the maximum intracellular concentration found at 3 to 8 and 5 to 15 min for iron-saturated and iron-free forms, respectively. Addition of colchicine had no effect on binding or internalization. These results suggest that endocytosis of lactoferrin by Jurkat cells occurs through a receptor-mediated process. Jurkat cells internalize lactoferrin monophasically with a first-order endocytic constant K(in) of 0.060 min-1 at 37 degrees C. Confocal microscopic analysis, using fluorescein-carbohydrate-labeled lactoferrin showed that lactoferrin was mainly localized in intracellular vesicles. Following uptake, the endocytic path utilized by fluorescein-carbohydrate-labeled lactoferrin was shown to diverge from that of rhodamine-labeled serum transferrin; after internalization, lactoferrin and serum transferrin did not fully colocalize. Intracellular lactoferrin was found in endosome vesicles as assessed by electron microscopy. Raising the pH in endosomes using chloroquine led to the accumulation of lactoferrin into endosomes (acidic compartment). After internalization, Jurkat cells released both degraded and intact lactoferrin into the culture medium, suggesting that a fraction (30-40%) of the ligand is degraded at each round of endocytosis.

Cell Line↗
PubMed1996

Induction by interferons of human eosinophil apoptosis and regulation by interleukin-3, granulocyte/macrophage-colony stimulating factor and interleukin-5.

The effects of recombinant human interferon alpha (rhIFN-alpha) and interferon gamma (rhIFN-gamma) were examined on the apoptosis of human cord blood derived eosinophils, obtained after 4 weeks of culture with recombinant human interleukin-3 (rhIL-3), granulocyte-macrophage-colony stimulating factor (rhGM-CSF) and interleukin-5 (rhIL-5). Eosinophil viability decreased remarkably after 1 week culture with rhIFN-alpha and rhIFN-gamma. Recombinant rhIFN-alpha also decreased the viability of co-existing monocytes/macrophages, whereas in contrast, rhIFN-gamma increased the percentage of viable monocytes/macrophages. There was no synergistic or additional effect of rhIFN-alpha and rhIFN-gamma on eosinophil viability. Apoptotic eosinophils, detected by their morphological characteristics, or by DNA nick end labeling in situ, increased remarkably after incubation with rhIFN-alpha and increased to a lesser extent with rhIFN-gamma. The numbers of eosinophil-phagocytosing macrophages increased after culture with rhIFN-alpha and also with rhIFN-gamma. In contrast, eosinophilopoietic cytokines such as rhIL-3, rhIL-5 and specially rhGM-CSF, significantly increased eosinophil viability, and partially rescued the effects of rhIFNs. They also decreased apoptotic eosinophil numbers and eosinophil-phagocytosing macrophage numbers. These results indicate that eosinophil viability, at least in vitro, can be differentially regulated by cytokines produced during the immune response.

Apoptosis↗
PubMed1995

Human eosinophils express a receptor for secretory component. Role in secretory IgA-dependent activation.

The existence of a functional receptor for secretory component (SC) on the eosinophil membrane might explain the preferential degranulation induced by secretory IgA (sIgA) when compared to serum IgA. Indeed, flow cytometry analysis revealed that purified human SC could bind to a subpopulation (4-59%) of blood eosinophils purified from 19 patients with eosinophilia. Binding of radiolabeled human SC could be competitively inhibited using unlabeled SC or secretory IgA but not with serum IgA or IgG. Immunoprecipitation and immunosorbent chromatography using human SC revealed the presence of a major component at 15 kDa in eosinophil extracts as well as in culture supernatants but not in neutrophils. The 15-kDa protein eluted from the human SC immunosorbent was able to bind to SC or to sIgA but not to serum IgA. Eosinophils preincubated with human SC or sIgA released eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) after addition of anti-SC or anti-IgA monoclonal antibody as respective cross-linking reagents. These results indicated that binding of free or complexed SC to human eosinophils could induce eosinophil degranulation. Furthermore, the dose-dependent inhibition by SC of mediator release induced by sIgA but not by serum IgA, suggested that the receptor for SC could be involved in the preferential degranulation mediated by sIgA. These results indicate a novel pathway of eosinophil activation and its potential involvement in mucosal immunity, particularly in inflammatory diseases associated with infiltration of eosinophils and the enhanced production of sIgA.

Binding, Competitive↗
PubMed1995

Eosinophils: from low- to high-affinity immunoglobulin E receptors.

Several experimental approaches have been used to identify immunoglobulin (IgE) binding molecules expressed by human eosinophils. After the description that Fc epsilon RII/CD23 identified on eosinophils could participate in IgE binding and IgE-mediated cytotoxicity, Mac2/epsilon binding proteins belonging to the S-type lectin family were also detected on human eosinophils. Anti-Mac2 monoclonal antibodies inhibited eosinophil-dependent cytotoxicity towards parasitic targets. More recently, Fc epsilon RI was demonstrated on human eosinophils from hypereosinophilic patients. The 3 components of Fc epsilon RI, alpha, beta and gamma chains, were detected in eosinophils. The alpha chain of Fc epsilon RI was shown to be involved in IgE binding to eosinophils and in the selective release of eosinophil peroxidase. The participation of Fc epsilon RI-bearing eosinophils in a protective immune response against a parasitic infection indicates a so far unsuspected function of Fc epsilon RI. The interactions between the different types of IgE binding molecules are discussed.

Antigens, Differentiation↗
PubMed1995

Parallel interleukin 5 synthesis by eosinophils in duodenal and skin lesions of a patient with dermatitis herpetiformis.

A 59 year old man is presented with a diagnosis of dermatitis herpetiformis. Duodenal and skin biopsy specimens from blisters of both recent and late onset were collected before treatment. Electron microscopy, immunohistochemistry, and in situ hybridisation were performed to analyse the presence of activated eosinophils and the local synthesis of interleukin 5 (IL5). Parallel state of eosinophil activation and IL5 synthesis was found in the duodenal mucosa with total flat mucosa and in skin vesicles of recent onset. It is suggested that duodenal and cutaneous eosinophils can synthesise IL5 and then participate in small bowel and skin lesions.

Dermatitis Herpetiformis↗
PubMed1995

Activated eosinophils and interleukin 5 expression in early recurrence of Crohn's disease.

Endoscopic recurrences after radical surgery for Crohn's disease are useful for studying the pathogenesis of initial lesions of Crohn's disease. Factors predisposing to recurrence are poorly understood, but it has been shown that eosinophilic infiltration of the neoileum may occur within a few weeks of resection. The aim of this study was to compare, in nine patients having an ileocolectomy, the infiltration of eosinophils and their activation state in normal and diseased areas of the neoileum, three months after surgery. Tissue eosinophils were studied by histochemical methods and electron microscopy. Mucosal expression of interleukin 5 (IL 5), an important eosinophil activating factor was studied using in situ hybridisation. Sixty per cent of patients had endoscopic recurrence at three months. Eosinophil infiltration was more pronounced in diseased than in endoscopically normal areas and was associated with a high expression of IL 5 mRNA. Ultrastructural analysis showed features of eosinophil activation, but no cytotoxic lesions of surrounding inflammatory or epithelial cells. This study suggests that local synthesis of IL 5 associated with eosinophil activation in the tissues could participate in early mucosal damage in Crohn's disease.

Adult↗
PubMed1994

Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion.

Interleukin 5 (IL-5) is the main factor that promotes the terminal differentiation of eosinophil progenitors (as indicated by colony formation assays), and enhances the effector capacity of mature eosinophils. IL-5 is produced by T lymphocytes, CD4-/CD8- and mast cells and recently, messenger (m)RNA of this cytokine has been identified in eosinophils from patients with coeliac disease, asthma, or eosinophilic heart diseases. In this study, IL-5 mRNA and immunoreactive IL-5 protein were detected in tissue and blood eosinophils from patients with eosinophilic cystitis or hypereosinophilic syndromes but not in Crohn's disease. By electron microscopy associated to immunogold staining, immunoreactive IL-5 was identified in eosinophilic granules. After stimulation with IgA-, IgE-, or IgG-immune complexes, blood eosinophils were shown, by immunocytochemistry and by enzyme-linked immunosorbent assay, to secrete IL-5. These observations demonstrate that eosinophils, under physiological stimulation, can release significant amounts of IL-5, which may contribute to local eosinophil recruitment and activation.

Cytoplasmic Granules↗
PubMed1994

High-affinity IgE receptor on eosinophils is involved in defence against parasites.

Parasitic infections are often associated with eosinophilia and high levels of immunoglobulin E (IgE). This observation has led to speculation that eosinophils and IgE may act together in the immune response against parasites. In support of this hypothesis, IgE and eosinophils participate in cytotoxic reactions directed against Schistosoma mansoni larvae in vitro. Furthermore, epidemiological studies have shown an inverse correlation between levels of specific IgE and rates of infection with Schistosoma. The low-affinity IgE receptor (Fc epsilon RII/CD23) was first incriminated in eosinophil activation. The fact that the high-affinity IgE receptor (Fc epsilon RI) is not only expressed on mast cells and basophils but also on Langerhans cells led us to investigate the presence of Fc epsilon RI on eosinophils. Here we show that Fc epsilon RI is expressed on eosinophils from hypereosinophilic patients, is involved in eosinophil degranulation, and participates in eosinophil-mediated cytotoxicity against S. mansoni. Our results indicate that Fc epsilon RI may play a major part in immune defence against parasites.

Animals↗
PubMed1994

Interleukin-5 messenger RNA and immunoreactive protein expression by activated eosinophils in lesional atopic dermatitis skin.

The main cellular sources of interleukin-5 (IL-5) are T lymphocytes and mast cells. Recently, IL-5 mRNA has been identified in eosinophils from patients with celiac disease, eosinophilic heart diseases, and asthma. In an attempt to determine whether IL-5 is generated by eosinophils in atopic dermatitis we have used i) in situ hybridization with 35S-labeled IL-5 RNA probe combined with immunohistochemistry using a monoclonal antibody (MoAb) (EG2) directed against the activated form of Eosinophil Cationic Protein (ECP) and ii) double-immunostaining with anti-IL-5 MoAb and polyclonal anti-ECP antibody. We found that dermal eosinophils from lesional atopic dermatitis skin express IL-5 mRNA and protein. Moreover, highly purified blood eosinophils were also labeled with anti-IL-5 antibodies. The expression of IL-5 by eosinophils in atopic dermatitis might suggest an autocrine pathway of eosinophil differentiation and activation.

Cytoplasm↗