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Biomedical subjects

A Capron

Publications and source records attributed to A Capron.

At least 361 records · Page 20Linked to original sources

[Identification in Plasmodium falciparum of a protein specifically binding human fibronectins].

A fibronectin binding protein (FnBp) was identified in 3H isoleucine labeled P. falciparum schizonts using affinity chromatography on human fibronectin (Fn) coupled to Sepharose 4B. After incubation of Nonidet-P 40 parasite lysate with Fn-Sepharose, elution was performed with SDS-PAGE buffer. Analysis of FnBp by SDS-PAGE demonstrated a major band which migrated with an apparent Mr of 70,000 under reducing conditions. This band was not found when human or rabbit IgG coupled Sepharose 4B were used instead of Fn as control.

Animals↗

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↗

Induction of a protective antibody-dependent response against toxoplasmosis by in vitro excreted/secreted antigens from tachyzoites of Toxoplasma gondii.

Toxoplasma gondii is a worldwide protozoan parasite which causes severe disease in congenitally infected children and in immunocompromised patients. Besides the well-defined cytoplasmic and membrane antigens of tachyzoites, we felt that excreted/secreted antigens could play a major role in the immune response. We first report the development of a well-controlled procedure for obtaining tachyzoite excreted/secreted antigens (E/SA) in cell-free incubation media. The E/SA immunogenic in human, rat and mouse toxoplasmosis were then characterized. The major E/SA recognized by human sera from the chronic phase of toxoplasmosis had molecular weights of 108, 97, 86, 69, 60, 57, 42, 39, 28.5, 27 and 26 kD. When injected into +/+ Fischer rats, E/SA elicited high antibody titres. In addition, passive transfer of these sera to highly susceptible nu/nu littermates induced a significant degree of protection towards the virulent RH strain of T. gondii. This work, which demonstrates the key role played by E/SA in the protective immune response, suggests that these antigens should be of value both for diagnostic purposes and for the development of new strategies for immunization against toxoplasmosis.

Animals↗

Properties of serine proteases of Schistosoma mansoni schistosomula involved in the regulation of IgE synthesis.

The regulation of IgE synthesis in vitro and in vivo by schistosomula-released products (SRP) has been shown to be dependent on the presence of serine proteases. The present paper concerns the characterization of the enzymes involved. The labelling of SRP with [3H]diisopropyl phosphofluoridate revealed two molecules, one major with an MW of 27,500 and one minor with an MW of 29,000. The same pattern was obtained by labelling of schistosomula or cercariae surfaces as well as of the total schistosomulum homogenate. The properties of these enzymes were studied by means of various specific substrates or inhibitors of serine proteases. The specificity was relatively narrow, but had some similarity with trypsin. When added to lymphoid rat cells in culture, SRP induced an increased expression of receptors for the Fc fragment of IgE (Fc epsilon RII). This suggests that the IgE-enhancing property of SRP was due to serine protease activity which may act by enhancing the lymphocyte Fc epsilon RII.

Animals↗

Immune response in chronic Schistosomiasis haematobium and mansoni. Reversibility of alterations after anti-parasitic treatment with praziquantel.

Peripheral blood mononuclear cells from Sudanese children heavily infected with Schistosoma haematobium and S. mansoni were examined for lymphocyte subpopulations, for mitogen and antigen responsiveness, and for natural killer (NK) cell activity before and 5 months after treatment with praziquantel. The humoral immune response was simultaneously investigated by determination of parasite-specific IgG and IgE antibodies, IgE-containing circulating immune complexes, and circulating schistosome antigen. A single dose treatment with praziquantel (40 mg/kg) resulted in a normalization of numerical imbalances in lymphocyte subpopulations, a significant increase in the blastogenic response upon stimulation with adult worm antigen, phytohaemagglutinin (PHA), and concanavalin A (Con A), and restoration of natural killer (NK) cell-mediated lysis of K562 targets. These findings were paralleled by a remarkable decrease in parasite-specific IgE antibodies, IgE-containing circulating immune complexes, and circulating schistosome antigen. The results indicate that the modulation of immune responses in chronic schistosomiasis is associated with active infection and is reversible after successful chemotherapy.

Antibodies, Helminth↗

Fluorescence-activated cell-sorting analysis of fibronectin peptides binding to Trypanosoma cruzi trypomastigotes.

The binding of synthetic peptides modeled from the sequence of the cell attachment site of fibronectin to T. cruzi trypomastigote surface receptors was investigated by fluorescence-activated cell-sorting analysis using fluorescein-labeled peptides. Peptides with the sequence Arg-Gly-Asp-Ser bound to the parasite surface. A low percentage of fresh parasites recently liberated from infected fibroblasts had the capacity to bind the peptide. In contrast, these parasites showed a time-dependent several-fold increase in their ability to bind the Arg-Gly-Asp-Ser-containing peptides during extracellular incubation. From these observations, it appears that the expression of surface receptors on a particular, mature stage of the parasite parallels its ability to adhere to and infect host cells.

Amino Acid Sequence↗

Variation in the expression of macrophage Fc epsilon receptors in relation to experimental rat schistosome infection.

The relationship between IgE and rat peritoneal macrophages during the course of Schistosoma mansoni infection was examined. Immune macrophages exhibited an IgE-dependent schistosomulicidal activity mainly between the 5th and the 7th weeks. At this period the percentages of anti-IgE rosettes whose variations appeared consecutive to the variations in the serum IgE level were higher. Following incubation in a serum-free medium immune macrophages could release membrane-associated IgE, to a certain extent, and consequently formed rosettes with IgE-coated erythrocytes, indicating the existence of Fc epsilon receptors. Thus, in terms of rosettes, their number varied in the course of the disease. In fact IgE-rich serum (i.e. at day 42) as IgE molecules could induce this macrophage Fc epsilon receptor. Moreover when transferred to syngeneic rats in association with parasite-specific IgE Fc epsilon R2+ macrophages led to some protection against challenge infection. All the data reported here emphasize the determining role of macrophages and IgE in immunity to schistosomiasis.

Animals↗

Regulation of IgE-dependent antiparasite functions of rat macrophages and platelets by nedocromil sodium.

The IgE-dependent stimulation of mononuclear phagocytes and blood platelets can be measured by antiparasite cytotoxicity, oxygen-mediated chemiluminescence and, in macrophages, lysosomal enzyme activity. Using these parameters, the present study demonstrated an inhibition by nedocromil sodium of the IgE-mediated triggering of the nonmast cell inflammatory populations in the rat. These observations suggest that nedocromil sodium may be of value in the modulation of IgE-dependent cell activation inducing the release of inflammatory mediators.

Animals↗

Inhibition by nedocromil sodium of IgE-mediated activation of human mononuclear phagocytes and platelets in allergy.

The demonstration of a specific receptor for IgE on nonmast cell or basophil leukocytes, such as mononuclear phagocytes, eosinophils, and platelets, suggests that these cells may participate directly in immunological disorders of allergy. Thus, a full understanding of the mode of action of antiallergic or antiasthma drugs must take into account their activity on these nonmast cell leukocytes. Consequently, inhibition by nedocromil sodium of IgE-dependent activation of human alveolar macrophages, blood monocytes and platelets, was investigated. This compound induced an inhibition of the IgE-mediated generation of cytotoxic molecules from monocytes and platelets, together with a concomitant inhibition of their oxidative metabolism, measured by chemiluminescence, and a reduction of the potential ability of alveolar macrophages to synthesize and release mediators, estimated by lysosomal beta-glucuronidase activity. These observations confirm the hypothesis that nedocromil sodium acts on a cell compartment other than the classical mast cell population, in IgE-dependent allergy and, more particularly, in asthma.

Airway Obstruction↗

IgE-dependent killing of Brugia malayi microfilariae by human platelets and its modulation by T cell products.

Platelets isolated from patients infected with filariasis were cytotoxic for microfilariae in vitro. Moreover, platelets from normal donors acquired killing properties in the presence of serum from infected individuals. The humoral factor involved in this cytotoxic process was shown to be IgE. This IgE-dependent cytotoxicity of platelets was strongly inhibited by antigen-stimulated T lymphocyte supernatants from filarial patients.

Animals↗

Trypanosoma cruzi: fibronectin promotes uptake of epimastigote culture forms by human neutrophils and monocytes.

Treatment of human neutrophils and monocytes with human plasma fibronectin (Fn) enhanced their association with Trypanosoma cruzi epimastigote culture forms, a stage of parasite which activates the alternative complement pathway, and this related to the concentration of Fn in the culture medium. By increasing the incubation time, the parasite interiorization by phagocytic cells was observed. An enhancing effect of this latter phenomenon was obtained in the presence of Fn, while the addition of anti-Fn antibodies exerted an inhibitory effect. Moreover, the velocity of phagocytosis of complement-coated epimastigotes in the presence of Fn appeared greater than that observed using non-coated epimastigotes or parasites preincubated in the presence of heat-inactivated C6-deficient rabbit serum. In addition, as a consequence of cell-Fn parasite interaction, cell activation was also seen. This has been demonstrated by a chemiluminescence assay. Using radiolabeled epimastigotes (3H-uridine), we demonstrated that a proportion of ingested parasites in the presence of Fn were killed. When neutrophils were used as effector cells, the cytotoxicity was greater than that observed with monocytes. This finding of increased trypanosome uptake by phagocytic cells in the presence of fibronectin suggests that this glycoprotein could act as a ligand or cofactor to mediate parasite-cell interaction.

Animals↗

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↗

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↗

IgE-dependent killing of Schistosoma mansoni schistosomula by human platelets: modulation by T cell products.

The in vitro stimulation of T lymphocytes is known to induce the release of factors that possess distinct biological activities. In the present report, we describe the presence, in supernatants of Schistosoma mansoni antigen stimulated T cells from S. mansoni infected patients, of a factor able to inhibit the IgE-dependent platelet cytotoxicity of the same individuals toward the young larvae of S. mansoni.

Animals↗

Production of an interleukin-1 inhibitory factor by human alveolar macrophages from normals and allergic asthmatic patients.

In order to study the possible role of alveolar macrophages (AMs) in the development of local immune responses, we compared interleukin-1 (IL-1) production by peripheral blood monocytes and AMs from 17 allergic asthmatics and 32 controls. When stimulated by lipopolysaccharide, alveolar macrophages and blood monocytes from controls released IL-1 (127 +/- 74.6 and 178.8 +/- 120 IL-1 units/ml, respectively) in the same amounts as AMs and blood monocytes from allergic asthmatics (148 +/- 47.5 and 160.5 +/- 78.3 IL-1 units/ml, respectively). After stimulation by anti-IgE or the specific allergen, asthmatic blood monocytes released IL-1-like activity (71.8 +/- 46.4 and 45.4 +/- 25.9 IL-1 units/ml, respectively). In contrast, asthmatic AM supernatants contained no detectable IL-1-like activity after stimulation by allergen or anti-IgE. The same pattern was observed with monocytes and AMs from controls after passive cell sensitization with 20% of IgE-rich serum. In a second step, the effect of supernatants of IgE-dependent stimulated AMs was tested on thymocyte proliferation induced by a purified IL-1, permitting the demonstration of an IL-1 inhibitory factor released by the AMs while these supernatants didn't modify the IL-2-dependent proliferation of a CTL-L line. The use of indomethacin and assessment of PGE2 levels in AM supernatants made it possible to discard the role of prostaglandins in this inhibitory effect. Moreover this activity, which is resistant to heat and trypsin treatment, has a molecular mass between 40 and 50 kD and did not correspond to serum proteases, alpha-1-antiproteinase, and arginase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

IgE-dependent humoral immune response in Echinococcus multilocularis infection: circulating and basophil-bound specific IgE against Echinococcus antigens in patients with alveolar echinococcosis.

Clinical symptoms of immediate-type hypersensitivity (ITH) and specific IgE against Echinococcus granulosus antigens are frequently present in patients with hydatid cysts. In alveolar echinococcosis (AE) due to E. multilocularis, clinical manifestations related to ITH have never been reported. The IgE-dependent humoral immune response was evaluated in 30 patients with AE. Circulating specific IgE (sIgE) were determined with two different methods of radio-allergo-sorbent test. Serum sIgE were determined sequentially in 18 patients over 15 months. Specific IgE bound to circulating basophils were assessed with two tests in vitro, measuring specific degranulation and histamine release. The respective abilities of E. granulosus and E. multilocularis antigens to reveal bound and circulating IgE antibodies were also assayed. Despite the absence of clinical symptoms of ITH and the frequent lack of circulating sIgE, an immunological response involving IgE was always present in human AE: basophil-bound sIgE were revealed in every patient by histamine release and degranulation tests; these tests were constantly negative in control subjects. Echinococcus granulosus extracts were more effective for detecting circulating sIgE; however E. multilocularis antigenic preparation induced a histamine release significantly higher than E. granulosus extracts. These results suggest that IgE-dependent humoral immune response could play a role in the host-parasite relationship in AE. Moreover, the sensitivity of the tests used to detect basophil-bound sIgE was higher than that of the usual serological tests, and the basophil degranulation test could be used to confirm diagnosis of AE in endemic countries.

Adult↗

[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↗