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Biomedical subjects

A Capron

Publications and source records attributed to A Capron.

At least 343 records · Page 19Linked to original sources
PubMed1989

[Prospects of vaccination against schistosomiasis].

Schistosomiasis, the second parasitic infection in the world, might well be the first for which a vaccine could be proposed. Investigations on the mechanisms of protective immunity have allowed the characterization of target antigens, but also revealed that susceptibility to reinfection depends on the production of blocking antibodies. A genetic engineering-produced schistosome protein (P28) is presently the most potent antigen for the induction of a protective immune response in all the experimental models, including non-human primates.

Humans↗
PubMed1988

IgA antibodies against P30 as markers of congenital and acute toxoplasmosis.

Specific IgA antibodies against P30, a major surface protein of Toxoplasma gondii were sought in 198 serum samples (from 133 patients) by means of a double-sandwich enzyme-linked immunosorbent assay. These antibodies were detected in all cases of acute toxoplasmosis but in no cases of chronic toxoplasmosis nor in seronegative patients. They were not detected in samples from patients with "natural IgM antibodies" or in those containing rheumatoid factor or antinuclear antibodies. Among 26 infants whose mothers were infected during pregnancy, anti-P30 IgA antibodies were exclusively detected in the samples from the 8 infected infants, although anti-P30 IgM antibodies were detected in only 3 of the infected infants. No uninfected infant had IgA, though 5 had IgM at birth. Thus, the detection of IgA anti-P30 antibodies seems a better means than the detection of IgM antibodies of identifying infected infants, which is very important for treatment. In addition, the very early detection of IgA antibodies may be important for the diagnosis of acute toxoplasmosis, especially during pregnancy and perhaps also in patients infected by human immunodeficiency virus.

Acute Disease↗
PubMed1988

Analysis of T and B cell epitopes of the Schistosoma mansoni P28 antigen in the rat model by using synthetic peptides.

The Schistosoma mansoni P28 molecule is an Ag inducing protective immunity in various experimental models. Three synthetic peptides, derived from the primary sequence of the recombinant P28 and comprising amino acids 24-43, 115-131, and 140-153, respectively, were synthesized according to their hydrophilicity, mobility, and accessibility profiles. The presence of B and T lymphocyte epitopes in these peptides has been examined in the rat model. The results showed that the 24-43 and the 115-131 peptides contained major epitopes for IgG but not for IgE. Moreover, the 24-43 peptide-specific IgG produced after injecting either the recombinant P28 Ag or the 24-43 peptide coupled to tetanus toxoid was essentially of the IgG2a subclass and to a lesser extent of the IgG1 subclass, whereas no IgG2c was detected. These 24-43 peptide-specific antibodies were cytotoxic in vitro for schistosomula in the presence of eosinophils as effector cells. The 24-43 and the 140-153 peptides contained major targets of T lymphocytes specific for the recombinant P28 Ag. T cell lines specific for the 24-43 peptide have been prepared. These cells proliferated in vitro when stimulated with various S. mansoni crude antigenic preparations or with the recombinant P28 Ag. Moreover, their passive transfer to rats immunized with the P28 Ag led to a significant increase in specific IgE without modifying the IgG response.

Animals↗
PubMed1988

Protective role of IgE in immunocompromised rat toxoplasmosis.

In contrast to euthymic adult Fischer rats, immunocompromised Nu/Nu animals develop a lethal infection when inoculated with the RH strain of the protozoan Toxoplasma gondii. However, a significant period of survival is obtained when Nu/Nu rats are passively transferred with sera from 28-day infected Fischer +/+ (euthymic) animals. Specific IgE are involved since IgE-depleted sera are unable to afford such a protection. Only excreted/secreted Ag or living tachyzoites are able to induce a significant protective IgE response in intact animals. In addition, platelets or, to a lesser extent, eosinophil-rich populations from Toxoplasma infected or excreted-secreted Ag-immunized euthymic animals bear surface IgE and are cytotoxic for the parasite in vitro. Also, adoptive transfer of immune platelets confers a significant degree of protection to Toxoplasma-infected Nu/Nu animals. Our results clearly show the key role of Ag present in both living parasites and excreted-secreted Ag to induce, in this model, a protective IgE response. In addition, as in other parasitic infections, platelets and probably eosinophils are the effector cells involved in controlling parasitic dissemination during Toxoplasma infection in immunocompromised rats.

Animals↗
PubMed1988

Onchocerca volvulus. Monoclonal anti-idiotype antibody as antigen signal for the microfilaricidal cytotoxicity of diethylcarbamazine-treated platelets.

Over the past 35 yr, diethylcarbamazine (DEC) has been the most widely used agent for the treatment of filarial diseases, particularly in onchocerciasis. The microfilaricidal action of DEC has been recently shown to be mediated by blood platelets with the additional triggering of a filarial excretory Ag (FEA). This FEA could be detected by using mAb in the serum of infected patients. By using one mAb (IA2(23] directed against Onchocerca volvulus and recognizing circulating Ag (Ab1), we purified by affinity chromatography the target molecule of IA2(23) (an O. volvulus glycoprotein recognized by IA2(23) mAb). This compound had a dose-dependent effect on the cytotoxic action of DEC-treated platelets. We subsequently produced an anti-idiotype mAb to Ab1 (Ab2), and considered the possibility of replacing the O. volvulus glycoprotein recognized by IA2(23) mAb by Ab2. Ab2 was selected according to its ability to inhibit the binding of radioiodinated Ab1 to the filarial target Ag. It induced the production of anti-O. volvulus antibodies (Ab3) in rats. At a constant concentration of DEC platelets, the addition of increasing amounts of Ab2 led to a dose-dependent cytotoxic effect against parasite larvae. Experiments performed with Ab2 on detergent solubilized surface proteins of platelets identified four bands of Mr 18, 26, 43.5, and 100 kDa, supporting the idea of the presence of binding sites on the platelets for a FEA required for the microfilaricidal cytotoxicity of DEC-treated platelets.

Animals↗
PubMed1988

Recombinant tumor necrosis factors mediate platelet cytotoxicity to Schistosoma mansoni larvae.

The involvement of platelets in the immunity directed toward the parasite Schistosoma mansoni has been demonstrated in vitro and in vivo. The killing properties of platelets were shown previously to involve specific IgE after their binding to a membrane receptor. More recently, we have demonstrated that lymphokines released by S. mansoni Ag- or lectin-stimulated CD4+/CD8-T cells were able to induce the platelet cytotoxicity. The isoelectric focusing of the T lymphocyte supernatants showed that two factors were able to stimulate the platelet killing functions. One of them was clearly identified as being IFN-gamma. The present work demonstrates that the second lymphokine was TNF. Indeed the rTNF-beta and, to a lesser extent, rTNF-alpha, induce normal platelets into killer cells for the young larvae of schistosome. Moreover, an additive effect of the TNF-alpha and IFN-gamma has been observed.

Adult↗
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

The major surface protein of Leishmania promastigotes is a fibronectin-like molecule.

The major surface glycoprotein of Leishmania chagasi promastigotes showed crossreactivity with fibronectin (Fn), a large glycoprotein that is a major constituent of the extracellular matrix of most mononuclear cells. Polyclonal and monoclonal antibodies against Fn precipitated two molecules of 63-58 kDa from the lysates of both 125I and [35S]methionine-labeled promastigotes. In addition, a monoclonal antibody against a 15-kDa fragment of Fn containing the Arg-Gly-Asp-Ser (RGDS) sequence and several polyclonal monospecific mouse antibodies against a synthetic RGDS peptide also recognized the above two molecules. The attachment of Leishmania promastigotes to mouse peritoneal macrophages in vitro was partially inhibited when promastigotes were treated with F(ab')2 fragment of an anti-Fn IgG. Identical results were obtained by saturating the Fn receptors on macrophages using different peptides containing the RGDS sequence. Moreover, antigen preparations rich in glycoprotein 63 could efficiently promote the attachment and spreading of 3T3 mouse fibroblasts to surfaces coated with the antigen. These results clearly suggest that the gp63 of L. chagasi promastigotes is an Fn-like molecule that shares certain biological and molecular characteristics with Fn.

Animals↗
PubMed1988

Recombinant human interferon-gamma induces increased IgE receptor expression on human platelets.

Human recombinant interferon-gamma (IFN-gamma) significantly increased the expression of receptors for IgE (Fc epsilon RII) on blood platelets. Fc epsilon RII was measured by specific binding of 125I-labeled IgE or flow cytometry experiments. Scatchard analysis of 125I-labeled IgE binding curves revealed that treatment with IFN-gamma increased the number of Fc epsilon RII but did not change the value of the association constant of Fc epsilon RII for 125I-labeled IgE. IFN-alpha had no effect on the expression or affinity of Fc epsilon RII. In addition to Fc epsilon RII, IFN-gamma also modified the expression of the glycoprotein IIb-IIIa complex on the platelet membrane.

Blood Platelets↗
PubMed1988

Tolerance in rats by transplacental transfer of Dipetalonema viteae microfilariae: recognition of putative tolerogen(s) by antibodies that inhibit antigen-specific lymphocyte proliferation.

We have previously reported (Nature 1982. 299:361) that the transplacental transfer of Dipetalonema viteae microfilariae (mf) can induce an antigen-specific tolerance in rats. Rats thus tolerized have serum factor(s) which block(s) antigen-specific lymphocyte proliferation. The results of experiments involving fractionation of antisera from tolerant animals indicate that the inhibitory activity for antigen-specific blastogenesis resides in IgG antibodies. Absorption of IgG (eluted from protein A) with specific filarial antigens reduced the inhibition from 58% to 9% whereas a similar immunosorption of IgG size fraction (obtained by applying to AcA 34 Ultrogel) resulted in a decrease from 72% to 35%. This suggests that IgG size fraction might include factor(s) derived from mf and was partially blocking the blastogenic response. Since the tolerant animals harbor only mf, we have used radiolabeled mf surface antigens for immunoprecipitation by antisera from tolerant animals. Antibodies from tolerant animals have a different specificity for filarial antigens compared to those from immunocompetent and mf-resistant rats.

Animals↗
PubMed1988

Identification of anti-acetylcholinesterase and anti-idiotype antibodies in human and experimental Chagas' disease: pathological implications.

This report presents evidence that human acetylcholinesterase (AChE; acetylcholine hydrolase, EC3.1.1.7) exhibits immunological cross-reactivity with the protozoan parasite Trypanosoma cruzi. The immunological probes used indicate that the cross-reactive determinant is an oligosaccharidic epitope. Antibodies to AChE were detected in a high proportion of T. cruzi-infected patients sera and during the experimental infection of BALB/c mice. Moreover, anti-idiotypic antibodies against an anti-AChE rabbit antibody or a monoclonal antibody to a parasite surface antigen of 80-85 kDa were detected in sera of patients presenting the chronic cardiac form of the disease. The antibodies were less frequently found in sera from individuals with asymptomatic chronic infection. Our data may provide a biochemical basis for denervation hypersensitivity in Chagas' disease. In addition, it may support the notion of an idiotype-anti-idiotype regulation of conducting tissue damage during the course of T. cruzi infection.

Acetylcholinesterase↗
PubMed1988

Killer cells in human cutaneous leishmaniasis.

In French Guiana, American cutaneous leishmaniasis is localized in the skin. The host response appears to be effective since few extra- or intracellular organisms can be found in tissue lesions, and we never observed any cutaneous dissemination or visceral involvement. However, this response is not fully effective since lesions may last for months. By using immunoperoxidase techniques and monoclonal antibodies directed against various cell populations, we examined the local immune response in skin biopsies. We found a high percentage of cells with the K/NK phenotype, a variable but usually high percentage of cells with the T cell phenotype bearing TAC receptors, and moderate numbers of monocytes and B cells. These results suggest that K/NK cells could play a role in the local control of parasite dissemination.

Adult↗
PubMed1988

In vitro and in vivo immunomodulation by LF 1695 of human and rat macrophages and platelets in schistosomiasis.

The activity of the synthetic immunomodulator LF 1695 on the efficiency of two effector cell populations--macrophages and blood platelets--involved in IgE-dependent cytotoxic processes against parasites, was evaluated. Oxygen metabolite production and anti-parasite cytotoxic properties of both macrophages and platelets were increased following LF 1695 treatment in vivo (in rat) or in vitro (in rat and in man). The phagocytic properties of rat peritoneal macrophages were also potentiated by their in vitro incubation with the drug. In addition to these effector functions, the lysosomal enzyme content and the migration ability of rat peritoneal macrophages were stimulated after incubation with LF 1695. In the presence of the drug, rat macrophages were also shown to produce increased level of IL-1--measured by the mitogen-induced proliferation of murine thymocytes--when compared to unstimulated phagocytes. Finally, the oral treatment of rats with LF 1695, in the course of an experimental infection with schistosome parasites, induced a higher degree of immune protection (80%) against a challenge infection than untreated, infected control rats (40%). These results bring evidence of a stimulatory role for LF 1695 on immune effector functions of cells participating to defense mechanisms against multicellular pathogens.

Adjuvants, Immunologic↗
PubMed1988

Effect of disodium cromoglycate on inflammatory cells bearing the Fc epsilon receptor type II (Fc epsilon RII).

Disodium cromoglycate (DSCG) has well-established stabilizing properties on mast cells and basophils. However, the potential inhibitory effect of DSCG has been little demonstrated on the IgE stimulation of cell populations expressing epsilon receptors type II, (Fc epsilon RII), such as mononuclear phagocytes, eosinophils or platelets. Therefore, using various parameters of IgE-mediated triggering, we demonstrated the inhibitory role of DSCG on: (i) the release of neutrophil chemotactic factor by human alveolar macrophages, (ii) the oxygen metabolite-dependent chemiluminescence of human alveolar macrophages, rat peritonal macrophages, human eosinophils, human and rat platelets, and (iii) the beta-glucuronidase release and synthesis by human alveolar macrophages. The inhibition of IgE-dependent stimulation ranged from 60% to 80%, according to the cells and to the measured parameter. It could therefore be considered that the action of DSCG was not restricted to its effects on mast cells and basophils, but also on other cells expressing Fc epsilon R leading to a potential reduction of the physiopathological consequences of allergic asthma and, possibly, of the late phase reaction sometimes associated with the disease, insofar as these cells are involved.

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

Brugia malayi microfilariae share epitopes with Aedes aegypti.

Shared antigens between Brugia malayi and Aedes aegypti were studied. The experiments carried out with sera from infected Mastomys natalensis indicated that an immunological response against A. aegypti antigens (Mr 185, 35, 32 kDa) appeared often when animals became microfilaraemic and increased progressively in intensity during the time-course of infection. Sera of animals immunized with B. malayi reacted with the crude extract of mosquitoes and conversely, antibodies from animals immunized with A. aegypti reacted with the surface of B. malayi microfilariae. The implications of these findings of the natural history of B. malayi infection are discussed.

Aedes↗
PubMed1988

Identification and isolation of Trypanosoma cruzi trypomastigote collagen-binding proteins: possible role in cell-parasite interaction.

We have shown here that collagen type I bound efficiently to the trypomastigote surface. In addition, monoclonal and polyclonal antibodies against collagen types I and III inhibited the infection of fibroblasts by the parasite. These results suggested the presence of collagen-binding protein(s) on the parasite surface. This protein was identified from trypomastigote surface antigens using affinity chromatography on a Gelatin Ultrogel column (denatured form of collagen). These collagen-binding proteins were revealed as a low-affinity gelatin binding protein (LAG Bp) of 98 kDa, and a high-affinity binding protein (HAG Bp) of 58 and 68 kDa under non-reducing and reducing conditions respectively. In addition, HAG Bp and LAG Bp bound to collagen type I. The 58/68 kDa protein was purified to homogeneity on a wheat germ agglutinin Sepharose column. A polyclonal antibody to this glycoprotein, as well as a monoclonal antibody (McAb) 155D3 produced against the HAG Bp, immunoprecipitated two parasite surface antigens of 160 and 58 kDa under non-reducing conditions which migrated at a position of 80-85 and 68 kDa when reduced. However, only the 80-85 kDa component could be precipitated from [35S] methionine-labelled trypomastigote antigens under reducing conditions. The antibodies to the 58/68 kDa glycoprotein as well as McAb 155D3 diminished the invasion of fibroblasts by parasites. Taken together these results suggest that the same receptor binds fibronectin and/or collagen and that both the 80-85 and 58/68 kDa glycoproteins form part of the same receptor. These trypomastigote surface molecules may interact with the host cell fibronectin and/or collagen during the initial phase of parasite-cell recognition.

Animals↗