Search PubMed⌕ Search

Biomedical subjects

A Capron

Publications and source records attributed to A Capron.

At least 469 records · Page 26Linked to original sources
PubMed1985

Regulatory role of a tripeptide (TKP) from the second constant domain of immunoglobulin G--I. Inhibition of rat and human macrophage activities.

We have previously shown that peptides released after the cleavage of IgG by parasite proteinases were strong inhibitors of the macrophage effector functions against schistosome larvae. The results presented here demonstrate that a single tripeptide set, Thr-Lys-Pro (TKP), inhibits various macrophage functions and can be considered as an immunologically active peptide. Indeed, not only IgE-dependent cytotoxicity but also beta-glucuronidase release, chemiluminescence and ILI production were reduced when rat macrophages were previously incubated with TKP or some analogues. Moreover, chemotaxis and IgE-specific receptor expression were inhibited in both rat and human macrophages after treatment with TKP, without affecting the cell viability. The substitution or acetylation of Thr diminished or suppressed the inhibitory effect of TKP.

Animals↗
PubMed1985

Regulatory role of a peptide from the second constant domain of immunoglobulin G--II. In vitro effect on granuloma formation around S. mansoni eggs.

Previous studies have shown that hydrolysis of IgG by proteases secreted by S. mansoni schistosomula release peptidic fragments which inhibit various macrophage functions. Several peptides from the second constant domain of IgG reduced granuloma formation in vitro with spleen cells from mice infected by S. mansoni eggs of the parasite. The maximal inhibitory effect was obtained by the tripeptide Thr-Lys-Pro (TKP). Inhibition occurred at the early stage of the granulomatous response. Among the cells involved only the adherent cell population was inhibited by the peptide. In addition, TKP-inhibited macrophage migration towards soluble egg antigens (SEA), suggesting that the reduced granuloma reaction by TKP is the result of the interaction between the peptide and macrophages. Injection of TKP into infected mice reduced the in vitro granulomatous response obtained using their spleen cells. This suggests an in vivo interaction between TKP and cells from the monocyte lineage. Moreover, the substitution of TKP on its NH2 or COOH terminal (Acetyl-TKP and TKP-amide) did not affect its in vitro activity. The latter result is of particular importance in the in vivo application of the peptide, at present under investigation.

Amino Acid Sequence↗
PubMed1985

Attempts to manipulate specific responses to induce resistance to Schistosoma mansoni in Kenyan baboons (Papio anubis).

Attempts were made to manipulate specific responses of baboons to protect them from infection with Schistosoma mansoni. In Experiment 1, eosinophilia was induced in naive baboons with Trichinella spiralis larvae given intravenously before intraperitoneal injection of globulin fractions from S. mansoni-infected baboon sera and subsequent percutaneous exposure to S. mansoni cercariae. In Experiment 2, baboons with 8- or 32-week-old primary S. mansoni infections received T. spiralis i.v. before an S. mansoni challenge. In experiments 3 to 5 respectively, naive baboons received intramuscularly before challenge: formalin-fixed S. mansoni schistosomula, with Bordetella pertussis as an adjuvant; a preparation of S. mansoni adult worm teguments; and a preparation of IgE-immune complexes obtained from S. mansoni-infected rat sera, with Freunds Complete Adjuvant. Minor, but statistically insignificant, protection was obtained in Experiments 2 (32-week infections) and 3, but was far less than that given by intact, irradiated living vaccines. There are signs on the horizon of non-living vaccines protecting rodents against S. mansoni infection and it would be prudent, as with drugs, to test these in primates before proceeding to man. The results of our experiments, though essentially negative, should help the design of any future vaccine trials in primates.

Animals↗
PubMed1985

In vitro inhibition of Plasmodium falciparum merozoite invasion by human plasma fibronectin.

Human fibronectin isolated from citrated blood was tested for its ability to bind to Plasmodium falciparum by an indirect immunofluorescent assay using rabbit antiserum to human fibronectin. A positive reaction was observed on merozoites inside schizont-infected erythrocytes. The binding was not observed on non-parasitized red blood cells. The effect of human fibronectin on P. falciparum growth was further studied using an in vitro inhibition assay; 50% inhibition of parasite multiplication was obtained with approximately 100 micrograms/ml of human fibronectin. Slight inhibition was observed below 10 micrograms/ml. The significance of this finding is discussed.

Animals↗
PubMed1985

IgG response of rats and humans to the released products of schistosomula of Schistosoma mansoni.

The participation of products released from Schistosoma mansoni schistosomula (SRP-A) in the IgG antibody response of infected Brown-Norway rats and infected humans has been studied using immunoprecipitation with various antigenic preparations and in in vitro cytotoxicity assays. A large number of SRP-A molecules with a wide range of molecular weights was recognized by infected rat and human sera. Anti-SRP-A antibodies appeared in rat sera from day 28 after infection. In infected humans, a variable pattern of SRP-A recognition was observed between individuals. IgG antibodies obtained by immunization of rats with SRP-A without addition of adjuvants reacted with 3 major schistosomula surface proteins with molecular weights of 38, 32 and 21 kDa. These latter molecules were also revealed strongly by infected rat sera. Moreover, these antibodies were able to kill schistosomula in vitro in the presence of complement or eosinophils.

Animals↗
PubMed1985

Platelet mediated killing of larvae from different filarial species in the presence of Dipetalonema viteae stimulated IgE antibodies.

The platelets from normal rats interact with microfilariae of Dipetalonema viteae in vitro in the presence of antibodies leading to the killing of the parasite. The antibody involved in this reaction is identified as IgE because the absorption of immune rat serum on anti-rat IgE column or the pretreatment of platelets with anti-Fc epsilon receptor resulted in a significant reduction in the percentage of killing of microfilariae. This antibody, which mediates platelet activity towards microfilariae, appears early in the secondary infection and persists for a short period of time. This short-lasting IgE antibody is not apparently present in the form of large complexes since the supernatant but not the pellet after ultracentrifugation was able to mediate killing of microfilariae by platelets. IgE-dependent platelet-mediated parasite killing is neither stage- nor species-specific because the microfilariae (LI) of Brugia malayi or of Loa loa and infective larvae (L3) of D. viteae or of B. malayi were killed when they were incubated with the serum obtained from rats at day 8 after secondary infection with adult D. viteae worms. The results of the present study suggest that platelets can actively participate in the immunological killing of filarial larvae.

Animals↗
PubMed1985

Subspecies-specific surface antigens of promastigotes of the Leishmania donovani complex.

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns of proteins and externally exposed labeled surface constituents were analyzed in promastigotes of three etiological agents of kala azar (Leishmania donovani, HS70 strain from India; L. chagasi, Imperatriz strain from Brazil; L. infantum, ITMPA K263 strain from Morocco and MO strain from France). Coomassie blue-stained gels showed similar protein patterns for L. donovani and L. chagasi and a more distinct one for L. infantum. Surface radioiodination with two different methods, lactoperoxidase and IODO-GEN, gave identical autoradiographic patterns for each parasite. Four major labeled proteins with apparent Mr values of 65,000, 60,000, 50,000, and 26,000 were detected in both L. chagasi and L. donovani. However, the radioiodinated polypeptide pattern of L. infantum only showed two major bands with an apparent Mr of 62,000 and a doublet of 26,000 to 23,000. Immunoprecipitation of detergent extracts of labeled promastigote subspecies with immune sera from rabbits immunized with either L. chagasi or L. infantum and from patients and mice infected with these two parasites, as well as with a monoclonal antibody against the surface of L. donovani promastigotes, demonstrated that the surface antigenic expression of L. infantum is different from that noticed in the two other subspecies, which are similar. Immunofluorescence experiments with some of these antibodies confirmed these results. The present findings should be considered in taxonomic and immunological studies in visceral leishmaniasis.

Animals↗
PubMed1985

New functions for platelets and their pathological implications.

We have recently demonstrated in Schistosoma mansoni infection that rat and human platelets could very efficiently kill parasite larvae, both in vivo and in vitro. The study of this IgE-dependent platelet effector function has led us to several subsequent findings. They concern: (1) the existence of a specific receptor for IgE on the platelet surface; (2) its close association with a platelet membrane glycoprotein of essential functional importance, the GPIIb-IIIa complex; (3) the observation, in extrinsic allergic asthma, of an allergen-specific IgE-dependent platelet activation; (4) the identification, in aspirin-sensitive asthma, of a similar, but non-IgE-dependent, platelet activation selectively induced by cyclo-oxygenase inhibitors, and prevented by salicylate. Beyond their implication in anti-parasite immunity, these findings provide a basis for new insights on the participation of platelets in disease.

Animals↗
PubMed1985

Cytophilic IgE on human blood and tissue eosinophils.

Flow microfluorometry (FMF) was used to investigate the presence of cytophilic Ig (IgE or IgG) and the proportion of Fc receptor (Fc epsilon R or Fc gamma R)-bearing eosinophils among eosinophils from 21 hypereosinophilic patients. In 75% of the cases, it was possible to detect cytophilic IgE, significantly associated with serum IgE levels. Moreover, when lung and blood eosinophils were compared, the proportion of occupied Fc epsilon R was significantly increased on lung eosinophils, whereas very few cells had cytophilic IgG. This work provides further evidence that cytophilic IgE is not restricted to cells with high-affinity Fc epsilon R but can also be detected on the cell populations with low-affinity IgE receptors. These findings support the view that eosinophils can act as effector cells in immediate hypersensitivity reactions and in diseases associated with increased IgE production and hypereosinophilia.

Eosinophilia↗
PubMed1985

Aspirin-sensitive asthma: abnormal platelet response to drugs inducing asthmatic attacks. Diagnostic and physiopathological implications.

The pathogenesis of aspirin-sensitive asthma remains unknown. Using a new model of platelet activation, initially described as a response of platelets to IgE antibody-dependent stimuli, this study was designed to test the hypothesis of a possible involvement of platelets in aspirin-sensitive asthma. Washed platelets from 35 aspirin-sensitive asthmatics showed an abnormal in vitro response to cyclooxygenase inhibiting nonsteroidal anti-inflammatory drugs (NSAIDs)--aspirin, indomethacin or flurbiprofen--characterized by the generation of a cytocidal supernatant and (14 patients explored) a burst of chemiluminescence; these drugs had no similar effect on platelets from 31 controls (p less than 0.0001). It was shown that the abnormal platelet response to NSAIDs was not mediated by IgE. In contrast to platelets, aspirin-sensitive asthmatic leukocytes generated neither cytocidal factors nor chemiluminescence in the presence of NSAIDs. Sodium salicylate and salicylamide, which, though structurally similar to aspirin, do not inhibit cyclooxygenase and are well tolerated by aspirin-sensitive asthmatics, did not activate their platelets to release cytocidal factors. Moreover, preincubation of platelets with sodium salicylate, salicylamide or prostaglandin endoperoxide PGH2, highly prevented their abnormal response to NSAIDs (greater than 80%; p less than 0.0001). Since several lipoxygenase inhibitors (NDGA, esculetin), including inhibitors of both cyclooxygenase and lipoxygenase (ETYA, BW755c), did not activate patient platelets and prevented the subsequent abnormal response to NSAIDs, it is suggested that the abnormal platelet activation by NSAIDs is not only the consequence of an inhibition of cyclooxygenase, but also involves generation of lipoxygenase metabolites of arachidonate. Besides, platelets from 4 aspirin-sensitive asthmatics undergoing aspirin desensitization were found to have completely lost their abnormal responsiveness to NSAIDs. These findings represent the first identification in aspirin-intolerant asthmatics of a specific abnormal cellular response to drugs inducing asthmatic attacks and open new perspectives into the pathogenesis, prevention and diagnosis of this disease. They also provide support to the concept of a role for platelets in asthma.

Adult↗
PubMed1985

Serodiagnosis of toxoplasma infection using a purified parasite protein (P30).

The major surface protein (P30) of Toxoplasma gondii has been purified by immunoabsorption with anti-P30 monoclonal antibodies linked to a glutardialdehyde activated affinity absorbant. SDS-PAGE analysis of the eluted material followed by silver staining showed only a single band of 30,000 mol wt. Western blotting using antibodies from a rabbit immunized with purified P30 against the total Toxoplasma extract separated by SDS-PAGE again revealed an unique antigen of 30,000 daltons. The presence of repeated epitopes within P30 was confirmed by a two-site/one-antibody radiometric assay with the purified protein. Sandwich ELISA procedures with purified P30 clearly demonstrated that all 37 tested patients with acute toxoplasmosis presented significantly high levels of IgM anti-P30 antibodies. In addition, all 40 tested patients with chronic toxoplasma infection also showed high IgG anti-P30 antibody levels. These findings represent an essential step for the development of new reagents for the diagnosis of toxoplasmosis.

Antigens, Protozoan↗
PubMed1985

Specific Schistosoma mansoni rat T cell clones. I. Generation and functional analysis in vitro and in vivo.

In an attempt to determine the role of schistosome-specific T cells in the immune mechanisms developed during schistosomiasis, Schistosoma mansoni-specific T cells and clones were generated in vitro and some of their functions analyzed in vitro and in vivo in the fischer rat model. The data presented here can be summarized as follows: a) Lymph node cells (LNC) from rats primed with the excretory/secretory antigens-incubation products (IPSm) of adult worms proliferate in vitro only in response to the homologous schistosome antigens and not to unrelated antigens (Ag) such as ovalbumin (OVA) or Dipetalonema viteae and Fasciola hepatica parasite extracts. b) After in vitro restimulation of the primed LNC population with IPSm in the presence of antigen-presenting cells (APC) and maintenance in IL 2-containing medium, the frequency of IPSm-specific T cells is increased and the T cells can be restimulated only in the presence of APC possessing the same major histocompatibility complex (MHC) antigens. c) Following appropriate limiting dilution assays (LDA) (1 cell/well), 10 IPSm-specific T cell clones were obtained, and two of four maintained in culture were tested for their helper activity because they expressed only the W3/13+ W3/25+ surface phenotypes. d) The two highly proliferating IPSm-specific T cell clones (G5 and E23) exhibit an IPSm-dependent helper activity, as shown by the increase in IgG production by IPSm-primed B cells. e) IPSm-T cell clone (G5) as well as IPSm-T cell lines when injected in S. mansoni-infested rats can exert an in vivo helper activity, which is characterized by an accelerated production of IgG antibodies specific for the previously identified 30 to 40 kilodaltons (kd) schistosomula surface antigens (Ag). As recent studies have demonstrated that rat monoclonal antibodies recognize some incubation products of adult S. mansoni as well as one of the 30 to 40 kd schistosomula surface antigens, and taking into account the fact that the T cell clones here studied were restimulated either with IPSm or with schistosomulum Ag, it appears that such IPSm-specific T cell clones could be involved in the concomitant immunity mechanisms.

Animals↗
PubMed1985

Cytophilic IgE on human blood and tissue eosinophils: detection by flow microfluorometry.

Flow microfluorometry (FMF) was used to investigate the presence of cytophilic Ig (IgE or IgG) and the proportion of Fc receptor (Fc epsilon R or Fc gamma R)-bearing eosinophils among eosinophils from 21 hypereosinophilic patients. In a large majority of the cases, it was possible to detect cytophilic IgE significantly associated with serum IgE levels. Moreover, when lung and blood eosinophils were compared, the proportion of occupied Fc epsilon R was significantly increased on lung eosinophils, whereas very few cells had cytophilic IgG. This work provides further evidence that cytophilic IgE is not restricted to cells with high affinity Fc epsilon R, but can also be detected on the cell populations with low affinity IgE receptors. These findings support the view that eosinophils can act as effector cells in immediate hypersensitivity reactions and in diseases associated with increased IgE production and hypereosinophilia.

Cell Separation↗
PubMed1985

Fc gamma receptors on rat eosinophils: isotype-dependent cell activation.

Fc receptors for rat IgG subclasses (IgG2a, IgG2c, and IgG1) were studied on rat eosinophils by rosette formation with erythrocytes coated with monoclonal immunoglobulin (Ig) or anti-Ig antisera in a reverse assay. Inhibition experiments revealed that IgG2a and IgG2c bind to the same receptor (IgG2a/IgG2c Fc receptor), distinct from the receptor for IgG1. In addition to the recent demonstration of the blocking effect of IgG2c antibodies in immunity to schistosomes, the present results show that the existence of this common receptor led to the specific inhibition by IgG2c of IgG2a-mediated eosinophil peroxidase release. Kinetic experiments on Schistosoma mansoni-infected rat eosinophils indicate that the IgG2a/IgG2c Fc receptors were occupied by cytophilic antibodies of the IgG2a isotype during the early phase of infection and by IgG2c thereafter. By rosette experiments it was possible to displace both in vivo and in vitro cytophilically bound IgG2a from its receptor. These results confirm, therefore, the major role played by antibodies in the modulation of eosinophil effector function during schistosomiasis. They underline, moreover, the possible isotypic regulation of cell activation.

Animals↗
PubMed1985

Resistance against Brugia malayi microfilariae induced by a monoclonal antibody which promotes killing by macrophages and recognizes surface antigen(s).

Several monoclonal antibodies were produced following the immunization of mice with infective larvae of Brugia malayi. One of these gives a positive fluorescence reaction on the surface of B. malayi microfilariae and this particular monoclonal antibody (IgM isotype) was able to mediate mouse peritoneal macrophage adherence to, and killing of, B. malayi microfilariae in vitro. Adherence and killing were enhanced by fresh normal mouse serum, suggesting a role for complement. When the same monoclonal antibody was passively transferred to mice harbouring microfilariae in their circulation, a complete clearance of microfilariae was observed in 70% of the animals. This monoclonal antibody was able to recognize antigenic determinants (of 110,000 MW) present on the surface of B. malayi microfilariae by radioimmunoprecipitation.

Animals↗