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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
PubMed1989

IgE and inflammatory cells.

Extensive studies initiated in parasitic disease models have unequivocally established that IgE antibodies can directly interact with mononuclear phagocytes, eosinophils and platelets through specific surface receptors now identified as Fc epsilon RII. Genes coding for B cell and more recently eosinophil IgE receptors have been cloned. Studies on molecular structure indicate a close homology between Fc epsilon RII on inflammatory cells and on B cells but indications are emerging of some degree of heterogeneity among the second class of receptors for IgE. Recent studies performed in parallel on eosinophils indicate that their IgE receptors contain a sequence commonly involved in the primary structure of adhesion proteins. Interaction between antigen and cytophilically bound IgE antibodies results in the triggering of cell effector function and the release of a variety of pro-inflammatory or cytocidal mediators. Among others, one eosinophil granule protein (eosinophil peroxidase) is preferentially released by anaphylactic isotype-dependent stimuli. The main expression of IgE-dependent platelet activation appears related to the production of oxygen-derived free radicals (detected by chemoluminescence and electron magnetic resonance) together with their cytocidal properties. Taken together these findings confirm our current view that IgE receptors on inflammatory cells play a major role in the expression of cell effector function, both in defence mechanisms against several parasites and in allergic reactions.

Animals↗
PubMed1989

Total and specific IgE in serum and cerebrospinal fluid of rats and guinea pigs infected with Angiostrongylus cantonensis.

The total and specific IgE response to Angiostrongylus cantonensis infection was evaluated according to host permissiveness. Total IgE levels measured by a double antibody radioimmunoassay (RIA) increased slowly in the permissive host (the rat), reaching a maximum between 4 and 8 weeks after infection. This maximum was earlier but significantly lower in the non-permissive host (the guinea pig). IgE antibodies specific for adult worms or L1 or L3 larvae of A. cantonensis were measured by a radioallergosorbent test (RAST). In the case of adult worms and L1 antigens, specific IgE antibody levels showed large variations in relation to the duration of infection in rats. In contrast to total IgE levels, the specific IgE response to L3 larvae was lower in rats than in guinea pigs in both the serum and cerebrospinal fluid (CSF). These results suggest variations in the total vs specific IgE response according to host permissiveness or non-permissiveness to A. cantonensis infection. These results are discussed in the context of the possible participation of IgE antibodies in immune defence.

Angiostrongylus↗
PubMed1989

Angiostrongylus cantonensis: role of eosinophils in the neurotoxic syndrome (Gordon-like phenomenon).

The role of eosinophils in the pathophysiology of Angiostrongylus cantonensis infections was investigated in nonpermissive (guinea pig) and permissive (rat) hosts. Neurological symptoms similar to the Gordon phenomenon (ataxia, tremor, paralysis) together with a loss of Purkinje cells in the cerebellum were observed after intracraneal injection of human eosinophil extracts or after infection with A. cantonensis, only in guinea pigs and not in rats. Blood eosinophilia as well as eosinophil numbers present in the cerebellum and in the cerebrospinal fluid were higher in guinea pigs than in rats, at all times after infection with A. cantonensis. Increased levels of cytotoxicity toward L3 larvae in vitro were obtained in the presence of guinea pig eosinophils and IgE antibodies, rather than with the corresponding rat effector system. The detection of one eosinophil granule component, the eosinophil peroxidase, in the cerebrospinal fluid from infected guinea pigs but not from rats suggested that in nonpermissive hosts, neurological disorders, similar to the previously described Gordon phenomenon, might be due to eosinophil neurotoxins released after interaction of eosinophils with the parasites.

Angiostrongylus↗
PubMed1989

Selectivity of mediators released by eosinophils.

The presence of receptors for IgE on eosinophils has drawn the attention on their direct participation in IgE-dependent hypersensitivity reactions. Surface IgE antibodies were detected on eosinophils from allergic patients. The addition of the specific allergen or anti-IgE antibodies to such purified eosinophils induced the release of eosinophil peroxidase, but not of eosinophil cationic protein. These findings associated with results obtained by using electron microscopy and immunogold staining of the various antibodies directed against the granule proteins allowed us to suggest a selectivity in the mediators released by eosinophils. In addition, preliminary results concerning the existence and the functional role of a receptor for IgA on eosinophils are reported, leading to the concept of a particular interaction of eosinophils with immunoglobulins present in the tissues and their participation in local immune responses.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Inhibition of human eosinophil chemotaxis and of the IgE-dependent stimulation of human blood platelets by cetirizine.

Cetirizine is a new anti-allergic compound with a potent, long-acting, and specific antihistaminic property. Strongly active in the therapy of urticaria and seasonal or perennial rhinitis, it has been shown to inhibit the in vivo eosinophil attraction at skin sites challenged with allergen in atopic patients. In the present work, we confirmed that, at a therapeutical concentration, this molecule had a potent inhibitory action in vitro on eosinophil chemotaxis induced either by N-formyl-Met-Leu-Phe or platelet-activating factor and also on the IgE-dependent stimulation of platelets. These observations appear in favour of a possible role for cetirizine in the modulation of inflammatory cell interactions in allergic processes.

Blood Platelets↗
PubMed1989

Heterogeneity of human eosinophil glucocorticoid receptor expression in hypereosinophilic patients: absence of detectable receptor correlates with resistance to corticotherapy.

Assessment of steroid receptor content in human neoplastic lymphoid cells or mammary tumour cells has been previously used to predict steroid sensitivity in various types of cancers. In the present study, we have evaluated the relationship between glucocorticoid receptor content and the glucocorticoid sensitivity of human eosinophils, since hypereosinophilic patients do not always respond favourably to glucocorticoid, particularly in the hypereosinophilic syndrome (HES). Blood or alveolar eosinophils obtained from seven patients (four with HES without leukaemic markers; two with parasitic diseases; and one with eosinophilic pneumonia) displayed the same specific glucocorticoid receptor content as normal eosinophils (7.58 +/- 1.31 x 10(3) versus 7.76 +/- 0.74 x 10(3) sites/cell). In contrast, glucocorticoid-binding sites were undetectable in purified eosinophils collected from seven HES patients with (n = 3) or without (n = 4) leukaemic markers, whilst their mononuclear cells and/or neutrophils bound glucocorticoid. In one HES patient, kinetic studies showed that blood eosinophils initially positive in glucocorticoid binding assays became negative with the subsequent appearance of leukaemic markers. The absence of specific glucocorticoid binding sites was correlated with the absence of glucocorticoid receptor proteins by the use of a specific anti-glucocorticoid receptor monoclonal antibody. Eosinophil sensitivity to glucocorticoid was investigated by the evaluation of glucocorticoid inhibition of eosinophil chemotaxis and by the clinical outcome of in vivo glucocorticoid therapy. Our data provide evidence of the heterogeneity of eosinophil glucocorticoid receptor expression. In addition, the presence of glucocorticoid receptors is a prerequisite for glucocorticoid activity, in vitro and in vivo, on cells of the eosinophil lineage.

Drug Resistance↗
PubMed1989

Eosinophils: receptors and mediators in hypersensitivity.

The presence of receptors for IgE on eosinophils has drawn attention to their direct participation in IgE-dependent hypersensitivity reactions. Surface IgE antibodies were detected on eosinophils from parasite-infected or allergic patients. The addition of the specific antigen or anti-IgE antibodies to such purified eosinophils induced the release of eosinophil peroxidase (EPO) and major basic protein (MBP), but not of eosinophil cationic protein (ECP). In contrast, ECP was detected after the addition of anti-IgG antibodies. Moreover, PAF-acether was only produced after IgE-dependent activation of hypodense eosinophils but not after IgG triggering. These results suggest a selectivity in the mediators (pre-formed and newly formed) released in response to IgE- or IgG-dependent activation of human hypodense eosinophils. Associated with preliminary findings obtained by using electron microscopy and immunogold staining, they bring new information concerning the mechanisms of release of eosinophil mediators. Finally, they underline the essential role of eosinophils in hypersensitivity reactions.

Animals↗
PubMed1988

Quantitative and qualitative analysis of the Fc receptor for IgE (Fc epsilon RII) on human eosinophils.

In order to characterize the Fc receptor for IgE (Fc epsilon RII) on human eosinophils, we have compared the binding of human IgE myeloma protein to that of a monoclonal antibody (mAb BB10) directed against a common antigenic determinant of the Fc epsilon RII present on eosinophils, platelets and macrophages. Scatchard analysis of the binding to human eosinophils of the BB10 mAb revealed a linear monophasic binding curve, with a binding affinity of 1.17 x 10(7) M-1 and a number of 10(5) binding sites per cell. Biochemical analysis of the human eosinophil Fc epsilon R, performed by immunosorbent chromatography with either BB10 mAb or IgE, showed under nonreducing conditions a major component of 200 kDa. Under reducing conditions, 3 peptide fragments were obtained, with molecular masses of 45-50, 23 and 15 kDa. Finally, comparative analysis suggested that the Fc epsilon RII of human eosinophils and of a human macrophage cell line (U937) are structurally related and differ from the high-affinity Fc epsilon RI present on basophilic granulocytes.

Animals↗
PubMed1988

Immunity in human schistosomiasis mansoni: cross-reactive IgM and IgG2 anti-carbohydrate antibodies block the expression of immunity.

We have previously reported that the slow development of immunity to reinfection after treatment of Schistosoma mansoni infections is partly attributable to the continued presence of 'blocking' antibodies in young, susceptible children. A further analysis of this phenomenon supports the hypothesis that such blocking antibodies can be of the IgG2 as well as the IgM isotype, and that they react with carbohydrate epitopes expressed both on egg polysaccharides and on schistosomulum surface antigens, of particular importance being those antigens that are shed from the schistosomulum surface during the early stages of maturation in vitro. Evidence is also presented that, in those patients lacking high levels of IgG2 blocking antibodies, resistance to reinfection after treatment is associated with the presence of other IgG isotypes against the same shed antigens.

Animals↗
PubMed1988

Isotypic restriction of the antibody response to human immunodeficiency virus.

HIV-infected individuals progress toward AIDS despite the early elicitation of a specific immune response. Analysis of the isotypic distribution of HIV-specific antibodies appears of special interest for two reasons: first, isotypic diversity is partly under the control of antigen-specific T-helper cells, the very cells infected by HIV; second, isotype determines antibody functions, effector (neutralization, antibody-dependent complement, or cell-mediated cytotoxicity) as well as blocking functions. We have investigated by Western blot analysis the isotypic profile of the antibody response to HIV structural proteins (env, gag, pol) and to the nonstructural protein F (3' orf), which is absent from the virion and might primarily target infected cells. In 115 asymptomatic individuals, infected by sexual contact (homosexual men) or intravenously (hemophiliacs), the response to gag-products was polyisotypic, including IgM, IgG1, IgG3 and IgA; the response to F was more restricted (IgM, IgG1, IgA) and the response to env strikingly restricted to the IgG1 isotype, suggesting different regulatory mechanisms in the B-cell response to these proteins. The isotypic distribution was also influenced by the route of infection, IgG4 and IgE (gag-specific) being exclusively elicited in the hemophiliac group. Finally, observations of potential diagnostic interest were made in a limited number of at-risk individuals; these included the presence of gag- and pol-specific IgM or IgA in the absence of any HIV-specific IgG isotypes; and the presence of gag- and F-specific antibodies in the absence of env-specific antibodies, suggesting the early occurrence of both isotypic and antigenic selection mechanisms during the course of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Inhibition of eosinophil chemotaxis by a new antiallergic compound (cetirizine).

The in vivo inhibitory effect of a new antiallergic, anti-H1 drug, cetirizine, on eosinophil attraction at skin sites challenged with various stimuli has been recently suggested. In the present work, we confirmed that this molecule, at therapeutical concentration, has a potent inhibitory action on eosinophil response to different chemoattractant mediators such as platelet-activating factor (PAF acether) and N-formyl methionyl leucyl phenyl alanyl in vitro. Another anti-H1 drug, polaramine, did not show this effect at the same concentration. These findings suggest that cetirizine in addition to its antihistaminic effect could also play a direct inhibitory effect on eosinophil recruitment. Moreover, cetirizine was not toxic for eosinophils and did not induce degranulation, as shown by the absence of peroxidase release. Comparison between cetirizine and a PAF acether antagonist (BN 52021) suggested that cetirizine did not act by a PAF receptor-blocking activity.

Cell Survival↗
PubMed1988

Influence of an Hymenolepis diminuta infection on IgE and IgA bound to mouse intestinal eosinophils.

Infection of mice with Hymenolepis diminuta, which is an 'exclusively' intestinal cestode, affects the number of eosinophils and non-eosinophilic cells with IgE or IgA on their surface in the lamina propria. Presence of IgE on eosinophils is basically a primary infection response, while after reinfection the response is primarily characterized by IgA. For IgE- as well as for IgA-bearing eosinophils the response is most abundant in the second quarter of the intestine which is the parasite's preferred habitat. For non-eosinophilic cells the effect is smaller and limited to the IgE-bearing cells, with the most significant effect in the second quarter of the intestine.

Animals↗
PubMed1988

[Existence and function of a receptor for immunoglobulin A on human eosinophils].

The existence of receptors for immunoglobulin A on human eosinophils is demonstrated by flow cytofluorometry. Between 5 and 60% of eosinophils purified from peripheral blood of hypereosinophilic patients are able to bind monomeric serum IgA. The addition of antihuman IgA antibodies to surface IgA-bearing eosinophils induces the exocytosis of peroxidase contained in the granules suggesting a cell activation due to IgA receptors. The inhibition of antiparasitic cytotoxicity by eosinophils preincubated with IgA under a polymeric form only, indicates the low affinity of IgA receptors as well as their participation in the effector function of eosinophils.

Animals↗
PubMed1988

Associated expression of CD1 antigen and Fc receptor for IgE on epidermal Langerhans cells from patients with atopic dermatitis.

The presence of Fc receptors for IgE on epidermal Langerhans cells (LC) from patients with atopic dermatitis (AD) was demonstrated by three different types of experiments. Firstly, cell-bound IgE on LC was removed by acid elution and restored by highly purified human myeloma IgE (IgE kappa). Secondly, after pepsin digestion of cell-bound IgE the number of LC staining with anti-human light chain (kappa, lambda) antibodies significantly decreased in contrast to the number of LC staining with anti-human epsilon heavy chain antibody. Thirdly, LC formed rosettes with sheep red blood cells (SRBC) coated with IgE kappa. Epidermal LC from normal non-atopic controls, did not form rosettes with SRBC-IgE. The SRBC-IgE rosette formation could be inhibited by preincubation with IgE kappa and BB10 (MoAb directed against the Fc receptor for IgE on human eosinophils, platelets and macrophages), but also with human IgG, whereas the SRBC-IgG rosette formation could be inhibited neither by IgE kappa nor by BB10. Both the SRBC-IgE and the SRBC-IgG rosette formation could be inhibited by OKT6 (anti-CD1) antibody. The results of inhibition studies with OKT6 antibody on the reconstitution of IgE on epidermal LC after acid elution suggest an associated expression of the CD1 antigen and the Fc receptor for IgE.

Antigens, Differentiation↗
PubMed1988

Eosinophilic gastroenteritis: ultrastructural evidence for a selective release of eosinophil major basic protein.

Ultrastructural study of mucosal eosinophils in a case of eosinophilic gastroenteritis involving stomach, duodenum and ileum showed an altered structure in ulcerated duodenal areas. The electron core density of eosinophil granules was inverted or disappeared and tubulovesicular structures occurred. Using immunogold staining with specific antibodies, major basic protein was detected diffusely in the matrix of eosinophil granules and out of the granules in tight association with extragranular membrane formations. In contrast, eosinophil cationic protein and eosinophil peroxidase were normally distributed in the granule matrix. When compared with the eosinophils in macroscopically normal duodenal mucosa in the same patient, these changes support a role for major basic protein in tissue damage in eosinophilic gastroenteritis. The diffusion of one granule protein from the granules to the exterior of the cells favours the view of a selective release of eosinophil mediators.

Adult↗
PubMed1987

Immunity to schistosomes: progress toward vaccine.

Among the major parasitic infections, schistosomiasis may be the most promising candidate for human vaccination. Information about mechanisms of immunity, gained mainly from experimental models but likely to be relevant to human infection, indicates a dynamic balance between protective and regulatory (blocking) mechanisms. Besides cell-mediated responses leading to macrophage activation, antibody-dependent cell-mediated cytotoxicity systems involving precise antibody isotypes and nonlymphoid cells (mononuclear phagocytes, eosinophils, and platelets) appear to be essential effectors of immune attack. The slow development of immunity in humans seems related to the production of antibodies that cross-react with schistosomulum surface antigen and block the binding of antibodies of the effector isotype. Schistosomes that survive in the bloodstream and produce chronic infections may evade the immune system as a result of intrinsic changes in membrane susceptibility and of transient expression of target antigens; at other stages of the parasite life cycle, cross-reactive molecules may be secreted that play an essential role in the induction of immunity. Several schistosome proteins have been characterized as candidates for vaccination. Among these, an antigen of 28 kilodaltons has been cloned and shown to be immunogenic in humans and protective in mice, rats, and baboons.

Animals↗
PubMed1987

Functional role of the alpha-chain of complement receptor type 3 in human eosinophil-dependent antibody-mediated cytotoxicity against schistosomes.

The participation of complement receptor type 3 (CR3) in antibody-dependent effector function of human eosinophils against parasites was studied by using monoclonal antibodies directed against various surface molecules. Both adherence and cytotoxicity of hypodense eosinophils to IgE-coated schistosomula of Schistosoma mansoni were strongly inhibited by anti-CR3 antibodies (OKM1 or Mo1). The specificity of the inhibitory effect for the alpha-chain of CR3 was shown by the lack of inhibition of anti-beta-chain or anti-LFA1 alpha-chain monoclonal antibodies, although these antigens were expressed on human eosinophils. These results associated to previous works on IgE receptors demonstrate that both receptor for Fc fragments of IgE and CR3 are essential in IgE-dependent cytotoxicity of human eosinophils. Flow microfluorometry analysis revealed that hypodense eosinophils were more intensively stained by OKM1 antibodies than the normodense populations. In the case of IgG-mediated cytotoxicity by normodense eosinophils, only the enhancement of cytotoxicity due to monokine activation was inhibited by anti-CR3 alpha-chain antibodies. These findings suggest an increased expression of CR3 on eosinophils after activation either in vivo or in vitro. The participation of CR3 in IgE-mediated cytotoxicity against schistosomes was also required in the case of blood monocytes but not for platelet-mediated killing, which does not require prior adherence. The biologic role of CR3 is therefore extended to effector mechanisms involving eosinophils and two different isotypes of antibodies and possibly implied in immunity against schistosomes.

Antibodies, Monoclonal↗