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Biomedical subjects

M Capron

Publications and source records attributed to M Capron.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1994

Elevation of soluble CD23 in serum from patients with blood eosinophilia.

The levels of soluble CD23 (sCD23) were evaluated by a two-site immunoradiometric assay in the sera of 41 patients with eosinophilia-associated disorders and 20 normal subjects. We observed that, in the absence of treatment, sCD23 levels were elevated in patients with eosinophilia-associated Gleich's syndrome, IgA deficiency, T lymphoma or hypereosinophilic syndrome (HES), but not in patients with a parasitic infection. A significant reduction in the sCD23 levels was found after treatment, with a parallel decrease in eosinophil counts and in sCD25 levels, a marker of disease activity in HES. The lack of increase in membrane CD23+ B cells in eosinophilic patients together with the detection of sCD23 in eosinophil supernatants suggest that activated eosinophils present in eosinophilia-associated disorders can release soluble molecules cross-reacting with CD23. In conclusion, our results suggest that eosinophils themselves can represent one cellular source of sCD23. These findings are not only basic but also of clinical interest.

Adrenal Cortex Hormones↗
PubMed1994

Evidence for eosinophil activation in eosinophilic cystitis.

Eosinophilic cystitis (EC) is a rare condition. Recent studies have shown that activated eosinophils release cytotoxic cationic proteins which can induce tissue damage. Moreover, in vitro studies have shown that interleukin-5 (IL-5) is a cytokine able to attract and activate eosinophils. The goal of this study was to detect a possible activation of eosinophils in EC using electron microscopy, in situ hybridization with an IL-5 RNA probe and immunochemistry with a specific anti-IL-5 antibody. Using these combined methods in a typical case of EC, we found numerous activated eosinophils synthesizing and secreting IL-5 protein. IL-5 could enhance the activation of eosinophils and their cytotoxic potential in bladder tissues. This mechanism might explain the chronicity of the lesions in EC.

Cystitis↗
PubMed1994

Development of a vaccine strategy against human and bovine schistosomiasis. Background and update.

Two specific characteristics of schistosome infection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive hosts (unlike protozoan parasites) and a partial non-sterilizing immunity can have a marked effect on the incidence of pathology and on disease transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reduction in parasite burden is a sufficient goal for vaccine induced immunity. We originally showed that IgE antibodies played in experimental models a pivotal role for the development of protective immunity. These laboratory findings have now been confirmed in human populations. Following the molecular cloning and expression of a 28 kDa protein of Schistosoma mansoni and its identification as a glutathione-S-transferase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction in parasite burden, vaccination with Sm28 GST was recently shown to reduce significantly parasite fecundity and egg viability leading to a decrease in liver pathology. Whereas IgE antibodies were shown to be correlated with protection against infection, IgA antibodies have been identified as one of the factors affecting egg laying and viability. In human populations, a close association was found between IgA antibody production to Sm28 GST and the decrease of egg output. The use of appropriate monoclonal antibody probes made it possible to demonstrate that the inhibition of parasite fecundity following immunization was related to the inhibition of enzymatic activity of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Immunolocalization of the lactotransferrin receptor on the human T lymphoblastic cell line Jurkat.

Monoclonal antibodies have been raised against the soluble lactotransferrin binding protein purified from the cell culture supernatant of Jurkat cell line, a human T-lymphoblastic cell. All monoclonal antibodies were able to specifically bind to the membrane of Jurkat cells. One of the monoclonal antibodies, DP5B3G10, recognized both the soluble lactotransferrin-binding protein and the membrane lymphocyte lactotransferrin receptor after SDS-PAGE in presence of 2-mercaptoethanol and electrotransfer on nitrocellulose. The monoclonal antibody DP5B3G10 inhibited the binding of lactotransferrin to Jurkat cells and human peripheral activated lymphocytes. In addition, lactotransferrin inhibited the binding of the monoclonal antibody to the cell surface. These results suggest that the 95 kDa lactotransferrin-binding protein isolated from the cell culture medium corresponds to the soluble form of the 105 kDa lymphocyte lactotransferrin receptor. Corresponding proteins of 105 kDa molecular mass were identified in Jurkat and CEM T-cells and Raji B-cells. Finally, the monoclonal antibody DP5B3G10 was used to immunolocalize the lactotransferrin receptor on the Jurkat cells. Using fluorescence and electron microscopy, the receptor was localized both inside and at the cell surface. The cell membrane receptor was associated into clusters. After permeabilization of the plasma membrane, the staining was positive in the peri-membrane area. The region near the nucleus was devoid of receptor.

Antibodies, Monoclonal↗
PubMed1994

[Eosinophil, beneficial or harmful: a cell entirely part of immune response].

The demonstration that human eosinophils could express various membrane receptors (for IgG, IgE, IgA; for complement; for cytokines; for chemotactic factors), for adhesion molecules (VLA4, LFAI, OKM1), as well as CD4 and class II MHC, has allowed to reconsider the role of eosinophils in immune response. Indeed, eosinophils can function as antigen presenting cells and can be infected by HIV. Studies on eosinophil mediators have revealed that eosinophils are not only the source of cytotoxic and proinflammatory mediators but can also release various cytokines and growth factors, including their own factors of differentiation (IL-3, GM-CSF and IL-5). The recent observation that eosinophils expressed IgE binding molecules belonging to different gene superfamilies (CD23, Mac2/epsilon BP and FceRI), as well as two different IgA receptors (Fc alpha R, and secretory component binding site), participating both in antiparasite immune defence and in inflammatory processes, reinforces the concept of the functional duality of eosinophils, specially in tissues.

Antibody Formation↗
PubMed1993

Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases.

Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.

Biopsy↗
PubMed1993

Ligation of CD23 triggers cyclic AMP generation in human B lymphocytes.

The low affinity IgE receptor CD23 may play a role in several B lymphocyte functions, such as cell activation and multiplication, Ag presentation, and IgE production. We have previously reported that ligation of the CD23 molecule with anti-CD23 mAb, or IgE-anti-IgE complexes, leads to phosphoinositide hydrolysis and calcium mobilization through the generation of Inositol (1,4,5) trisphosphate via a process involving a Pertussis toxin insensitive GTP-binding protein. In our work, we show that anti-CD23 mAb elicit an increase in cAMP concentration in human peripheral blood-derived B lymphocytes. This effect was detected both in resting and in IL-4-stimulated B cells displaying, respectively, low and high levels of CD23. Maximum cAMP accumulation was reached about 20 min after addition of the mAb. Involvement of Fc gamma RII in this process could be excluded because cAMP increase was also triggered by mAb anti-CD23 F(ab')2 fragments. Accumulation of cAMP was also observed when IgE-sensitized activated B lymphocytes were challenged with the specific hapten. Several lines of evidence indicate that the cAMP increase after CD23 ligation may result, in part, from the stimulation of phosphoinositidase C, inasmuch as it was markedly impaired by treatment with TMB-8, an inhibitor of InsP3-induced calcium release from intracytoplasmic stores and with BAPTA, an intracellular calcium chelator. Addition of GTP-gamma S to permeabilized B cells or to membrane preparations did not potentiate the effect of the mAb, suggesting that a Gs protein is not directly implicated in the generation of cAMP. Besides, cAMP accumulation is not due to the production of PG because it is not modified by indomethacin, an inhibitor of the cyclooxygenase pathway. Pretreatment of B lymphocytes with either anti-CD23 mAb or IL-4 led to autologous as well as heterologous desensitization. This negative cross-talk, at the level of cAMP, between the signaling pathways triggered by ligation of CD23 and of the IL-4 receptor, could contribute to the inhibitory effect of anti-CD23 mAb on IL-4-dependent B cell activation and differentiation.

Antibodies, Monoclonal↗
PubMed1993

IgA antibodies to a protective antigen in human Schistosomiasis mansoni.

The specific IgA antibody responses to the protective recombinant Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST) Ag and to derived synthetic peptides have been evaluated before and 6 mo after chemotherapy in S. mansoni-infected patients from Kenya. These studies revealed a parallelism between the age-dependent evolution of IgA antibody levels to Sm28GST and to one synthetic peptide (115-131) and the acquisition of resistance to reinfection. Functional analysis revealed that IgA antibodies to Sm28GST displayed a potent neutralizing effect on the enzymatic properties of the molecule, and also markedly impaired schistosome fecundity, by limiting both the egg laying of mature worms and the hatching capacity of schistosome eggs into viable miracidia. These results suggest that, in addition to IgE, IgA antibodies might participate in the protective immune response against schistosomiasis.

Adolescent↗
PubMed1993

Human neutrophils express immunoglobulin E (IgE)-binding proteins (Mac-2/epsilon BP) of the S-type lectin family: role in IgE-dependent activation.

It has been suggested that neutrophils may be involved in the late-phase reaction of immunoglobulin E (IgE)-dependent hypersensitivity states. However, the identity of neutrophil-associated molecules inducing the release of mediators remains unclear. In this report, we demonstrate that human neutrophils from normal donors or from patients with inflammatory disorders could bind myeloma IgE proteins, especially after desialylation. Northern blot, immunoprecipitation, and flow cytometry analyses revealed that neutrophils did not express Fc epsilon RII/CD23, but rather Mac-2/epsilon binding protein (BP), belonging to the S-type lectin family. Similarly to IgA used as positive control, myeloma IgE proteins, as well as polyclonal IgE antibodies with or without antibody specificity, were both capable of inducing a neutrophil respiratory burst. Anti-Mac-2 but not anti-CD23 mAb strongly decreased the IgE-dependent activation of neutrophils, induced either by the specific antigen or by anti-IgE antibodies. These findings open new perspectives on the functional role of neutrophils in IgE-associated diseases including allergic states or parasitic infections.

Antigens, Differentiation↗
PubMed1993

Protective immunity induced in rat schistosomiasis by a single dose of the Sm28GST recombinant antigen: effector mechanisms involving IgE and IgA antibodies.

Rats immunized by a single dose of the recombinant Sm28GST antigen, using either aluminium hydroxide or Bacillus Calmette-Guérin adjuvant, were significantly protected (up to 59% reduction in worm burden) against a challenge infection with Schistosoma mansoni cercariae. A follow-up study of the humoral response revealed the presence of high levels of IgE and IgA antibodies together with specific IgG. Sera from once Sm28GST-immunized rats induced a cytotoxic response for schistosomula targets in the presence of normal rat eosinophils, similar to the one induced by sera from twice immunized rats. Depletion or competition studies indicated the participation of both IgE and IgA antibodies in eosinophil-dependent cytotoxicity mechanisms. These results suggest the existence, in immunized rats exhibiting protection against schistosomiasis, of an original effector mechanism implying eosinophils and IgA antibodies, together with documented effector mechanisms involving IgE and eosinophils. In addition, they raise questions concerning the role of IgA antibodies in schistosomiasis.

Adjuvants, Immunologic↗
PubMed1993

IgE-binding molecules (Mac-2/epsilon BP) expressed by human eosinophils. Implication in IgE-dependent eosinophil cytotoxicity.

Macrophage cell-surface protein 2 (Mac-2), a galactose specific S-type lectin identified in inflammatory macrophages, presents a high degree of homology with the rat IgE-binding protein (epsilon BP). In the present study, we show by different experimental approaches that human eosinophils can express Mac-2/epsilon BP. Flow cytometry analysis revealed that a large proportion of eosinophilic patients expressing binding sites for IgE on their eosinophil membrane, were able to bind anti-Mac-2 monoclonal antibody (mAb). Northern blot performed with eosinophil RNA hybridized with the human Mac-2 or epsilon BP cDNA probes revealed that eosinophils presented a unique transcript at 1.2 kb. Immunoprecipitation of eosinophil extracts with anti-Mac-2 mAb revealed the presence of a molecule of 29 kDa corresponding to Mac-2 protein, as well as one additional molecule of 15 kDa, absent from control alveolar macrophages. The function of these molecules was investigated in a radiolabeled IgE binding assay. Anti-Mac-2 mAb as well as galactose and lactose saccharides significantly inhibited the binding of radiolabeled human myeloma IgE protein to eosinophils. Moreover, the dose-dependent inhibition by anti-Mac-2 mAb of IgE-dependent eosinophil-mediated cytotoxicity towards parasite targets indicated the role of these IgE-binding molecules in the function of human eosinophils. These results suggest that in addition to transmembrane receptors, lectin-type molecules can participate in the IgE-dependent effector function of eosinophils.

Animals↗
PubMed1993

Segregation of eosinophil proteins in alveolar macrophage compartments in chronic eosinophilic pneumonia.

BACKGROUND: The objective was to characterise the process and consequences of eosinophil activation and lysis in patients with chronic eosinophilic pneumonia and to compare them with those in patients with eosinophil pulmonary infiltrates from other causes. METHODS: Cells from bronchoalveolar lavage fluid of four patients with chronic eosinophilic pneumonia and four patients with eosinophilic infiltrates associated with Sjögren's syndrome, drug hypersensitivity pneumonia, postradiotherapy fibrosis, and pulmonary disease associated with graft versus host disease were studied ultrastructurally and with immunogold labelled antibodies directed against eosinophil proteins: major basic protein, eosinophil cationic protein, and Charcot-Leyden crystal protein. The concentration of eosinophil cationic protein was also measured in bronchoalveolar fluid. RESULTS: In the four patients with chronic eosinophilic pneumonia, ultrastructural studies demonstrated numerous lysed eosinophils. Further, three released eosinophil proteins were detected in distinct cytoplasmic structures in alveolar macrophages. These features were not found in the four patients with eosinophilic pulmonary infiltrates from other causes. CONCLUSION: Eosinophils in chronic eosinophilic pneumonia show signs of activation with release of eosinophil proteins. The appearance of three of these eosinophil proteins in different macrophage compartments suggests that macrophage uptake, with or without intracellular transport of released eosinophil proteins, involves separate mechanisms. This interaction does not lead to macrophage lysis, however, and one or more of these eosinophil proteins might directly affect macrophage function.

Adult↗
PubMed1992

Decreased expression of eosinophil peroxidase and major basic protein messenger RNAs during eosinophil maturation.

We evaluated the levels of mRNAs encoding cationic proteins in peripheral blood eosinophils (PBE) purified from patients with eosinophilia and in eosinophils differentiated from cord blood cells (CBC) by culture with recombinant human interleukin-3 (rhIL-3), rhGM-CSF, and rhIL-5. Messenger RNAs encoding eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) were detected by Northern blot hybridization with the respective specific oligonucleotide probes. In mature PBE, MBP mRNA appeared to be absent, whereas EPO mRNA was barely detectable in only 5 of the 19 patients. In contrast, EDN and ECP mRNAs were observed in the PBE of all patients. In CE, EPO, and MBP, mRNAs were abundant in immature eosinophils and their amounts decreased after differentiation toward eosinophils. ECP and EDN mRNAs followed the same patterns, but mRNAs were less abundant at all timepoints studied. Study of mRNA t1/2 during the time course of differentiation indicated that changes in the stability of the different mRNAs were not responsible for the variations observed in the steady-state levels. Together, these results suggest that regulation of expression differs among EPO, MBP, EDN, and ECP mRNAs during the time course of eosinophil differentiation.

Actins↗