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Biomedical subjects

C Auriault

Publications and source records attributed to C Auriault.

At least 109 records · Page 6Linked to original sources
PubMed1986

A suppressive lymphokine of platelet cytotoxic functions.

The in vitro stimulation of mononuclear cells from human peripheral blood with mitogens is known to induce the release of factors (monokines and lymphokines) that possess distinct biologic activities. The present data describe the presence in Con A- and antigen-stimulated T cell supernatants (of man or rat) of a factor able to inhibit, in a dose-dependent manner, the platelet cytotoxicity toward the young larvae of Schistosoma mansoni. The production of oxygen metabolites by IgE-coated platelets, stimulated by anti-IgE or the specific antigen, was, likewise, strongly inhibited by this lymphokine. The producing T lymphocyte subpopulation was identified as OKT 8+. This suppressive lymphokine of platelet functions had an m.w. of 15,000 to 20,000 and a pI of 4.6. It was heat- and acid-stable and sensitive to trypsin and proteinase K, but neuraminidase had no effect on its activity. This platelet suppressive activity was specifically absorbed by platelet membrane, suggesting its action through the binding to a receptor.

Binding, Competitive↗
PubMed1986

The receptor for IgE on blood platelets.

Highly purified blood platelets from man and rat could be induced into cytotoxic effectors against schistosome larvae by an IgE-dependent mechanism. Such a process implied the existence of a receptor for the Fc part of IgE on the surface of these blood elements. Normal platelets, incubated in the serum of infected individuals as well as in the IgE-rich serum from asthmatic patients, showed similar capabilities. Flow cytofluorometric analysis evidenced that the platelets bearing IgE receptors represented a subpopulation (20%), the percentage of which was significantly increased (up to 50%) in rats or patients with high levels of circulating IgE. Radiolabeled IgE, whose binding was specifically inhibited by an excess of unlabeled IgE or by anti-Fc epsilon receptor antibody, allowed the demonstration that the receptor for this isotype on the platelet surface was saturable. The binding of increasing amounts of IgE followed a bimodal curve, with less than 1000 sites per platelet showing an affinity coefficient of 3.3 X 10(7) M-1 at low concentrations, and a Ka of 7.8 X 10(5) M-1 for higher concentrations. Beyond their interest in the demonstration of cytotoxic properties of thrombocytes, these observations place emphasis on the potential role of the platelets in immediate-type allergic reactions by their direct interaction with IgE antibody molecules, through a specific receptor.

Animals↗
PubMed1986

Role of serine proteases of Schistosoma mansoni in the regulation of IgE synthesis.

The regulation of the IgE response by schistosomula-released products (SRP) was studied either in vitro with rat and human cell cultures or in vivo by injection into rats of SRP with an unrelated allergen at primary or secondary immunization. The results obtained in vitro showed that non-dialysable factors present in SRP potentiate the IgE synthesis by rat and human cells. This enhancing effect was supported by molecules with serine protease activities. On the other hand, the inhibition or depletion of SRP in serine proteases induced a weak synthesis of IgM by rat cells in vitro. The injection of SRP into rats on day 0 with an unrelated allergen led to a potentiation of total IgE production, but an inhibition of specific IgE response. In contrast, a marked elevation of specific IgE response was obtained when SRP was injected upon secondary immunization. Serine proteases of SRP were partly responsible for this potentiative effect.

Animals↗
PubMed1986

Induction of a protective immune IgE response in rats by injection of defined antigens of schistosomulum-released products: immunochemical properties of the target antigens.

Brown Norway rats were injected without adjuvant with the soluble products liberated in a 16-hour culture by schistosomula (schistosomula-released products, SRP-A). A strong cytotoxic and protective IgE response was elicited, mainly directed against 22- and 26-kilodalton (kDa) SRP-A molecules. In the present study, we have attempted to characterize further those molecules. Metaperiodate denaturing treatment of the SRP-A glycans before injection into rats did not modify the immunogenicity of the SRP-A antigens. Results obtained by lectin affinity suggested that the 22- and 26-kDa molecules were glycoconjugates binding to ConA. Preparative sodium dodecylsulfate electrophoresis has allowed the separation of enriched fractions of 22- and 26-kDa molecules which have been injected separately into rats. The corresponding sera were tested in antibody-dependent cell cytotoxicity and displayed a significant cytotoxic IgE response (65 and 53%, respectively) towards the larvae. These results lend further support to the view that the 22- and 26-kDa antigens are the major targets of the protective IgE response and thus appear as potentially protective antigens.

Animals↗
PubMed1986

Protection against experimental Schistosoma mansoni schistosomiasis achieved by immunization with schistosomula released products antigens (SRP-A): role of IgE antibodies.

Schistosomula-released products (SRP-A) have been shown to induce preferentially a significant IgE response against Schistosoma mansoni schistosomula when injected into rats, in the absence of adjuvant. The present work provides additional evidence of the in vivo relevance of the anti-SRP-A target antigens. Two strains of rat (Brown Norway and Fischer) were immunized with SRP-A and infected percutaneously. A significant level of protection (up to 83% reduction in worm burden) was observed. Passive transfer experiments carried out with anti-SRP-A or IgE-depleted anti-SRP-A sera suggested the preponderant role of antibodies and particularly of IgE in the protective immunity developed by Fischer rats. Platelets and macrophages recovered from such immunized rats had surface IgE as demonstrated by immunofluorescence analysis with FITC anti-IgE, and have been shown to be directly cytotoxic for schistosomula. The chemiluminescence observed when the macrophages were incubated with anti-IgE suggested the presence of IgE on the surface of these cells.

Animals↗
PubMed1986

Presence of factors chemotactic for granulocytes in hypereosinophilic syndrome sera: relation with alterations in eosinophil migration.

Recent work has underlined a structural and metabolic heterogeneity amongst blood eosinophils in various hypereosinophilic diseases. Little is known about the factors responsible for this variability. We have identified granulocyte chemotactic factors, termed GCFs in the sera of five patients with hypereosinophilic syndrome (HES). Sera from normal controls or from 20 patients with blood hypereosinophilia of various causes, but with little or no hypodense blood eosinophils, did not demonstrate any chemotactic activity. Two distinct GCFs were characterized, either by gel filtration or isoelectric focusing (molecular weights of 600 kD and 240 kD; pIs of approximately 5 and 7). These fractions are sensitive to proteolytic enzymes and to heating to 100 degrees C but not to 56 degrees C. The activity of GCFs has been tested towards neutrophils and eosinophils. The fractions of 240 kD and pI 7 appear more selective for the eosinophil lineage. Checkerboard analysis shows that such fractions are primarily chemotactic. In addition, hypodense eosinophils appear defective in random motility and chemotaxis towards chemotactic agents which are effective on normodense eosinophils. Moreover, preincubation of normodense eosinophils with HES sera rendered these cells unresponsive to very efficient chemotactic agents such as leukotriene B4 (LTB4) (decrease in migration of 91%; P less than 10(-3), formyl methionyl leucyl phenylalanyl (Fmlp) (decrease of 95%; P less than 10(-2)), HES sera (decrease of 91 to 93%). These findings suggest a process of deactivation of blood eosinophils with the possible retention within the circulation of activated hypodense eosinophils in HES.

Adolescent↗
PubMed1985

Defined antigens secreted by the larvae of schistosomes protect against schistosomiasis: induction of cytotoxic antibodies in the rat and the monkey.

The study of the immunology of schistosomiasis has allowed a clear understanding of the basic mechanisms of resistance, emphasizing the important role played by cellular and humoral factors. Whereas the production of polyclonal or monoclonal antibodies and the precise inventory of immune effector mechanisms in the rat and in man have led to the identification of potentially protective antigens, immunization with soluble schistosome components has not allowed a successful control of the destruction of schistosomula after infection. The experiments reported here show that schistosomulum-released products (SRP) were able to induce the production of antibodies, in the rat and the monkey, highly cytotoxic in antibody-dependent cellular cytotoxicity, using monocyte monolayers, platelets or eosinophils as effector cells. The immunization of rats with either total SRP or 25-30-kDa molecules purified from schistosomula conferred a significant protection towards a challenge infection by the parasite. IgE and to a lesser extent IgG antibodies represented the major humoral factors of cell activation leading to the schistosomulum killing when anti-SRP antisera, obtained after immunization of the monkey, were incubated with human effector cells.

Animals↗
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

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

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↗
PubMed1984

Rat IgE directed against schistosomula-released products is cytotoxic for Schistosoma mansoni schistosomula in vitro.

The immunogenicity of molecules shed by schistosomula into culture medium (antigens present in schistosomula-released products, SRP-A) has been studied. The results obtained show that SRP-A preferentially induce an IgE response when injected into rats, without the need for adjuvants. Moreover, anti-SRP-A IgE is cytotoxic in vitro for the larvae in the presence of macrophages, eosinophils or platelets, which have previously been demonstrated as being the three efficient killer cells for schistosomula in the presence of specific IgE. Immunofluorescence analysis locates the target antigens at the schistosomulum surface. Among the antigens recognized by anti-SRP-A IgE, two molecules of 26 and 22 kDa have been identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by western blotting.

Animals↗
PubMed1984

Non-specific potentiation of T- and B-lymphocyte proliferation at the early stage of infection by Schistosoma mansoni: role of factors secreted by the larvae.

The response of rat lymphocytes to schistosomula released products (SRP) was examined. SRP non-specifically activated lymphocytes by potentiating their proliferative response to PHA, Con A or LPS. The parasite factor involved was dialysable and heat stable. The addition of SRP to cultures containing nylon-wool non-adherent lymph node cells resulted in a significant enhancement of cell proliferation. The effect of SRP on athymic nude (Nu/Nu) and litter mate (Nu/+) control rat cells indicated an effect on the proliferation of both B and T lymphocytes. SRP acted in a dose-dependent manner and its action was observed as early as the beginning of cell division. This corresponds to the in vivo situation, since at the early stage of infection increased proliferative responses of the lymph node cells to mitogens were observed. The adjuvant effect of SRP could partly explain the regulation of the cellular immune response observed during S. mansoni infection by the parasite itself and could represent one of the mechanisms involved in immunity to reinfection that is under the control of the parasite.

Animals↗
PubMed1983

A new function for platelets: IgE-dependent killing of schistosomes.

Several killing mechanisms against schistosomes have been described in vitro, involving cellular and humoral factors. Neutrophils, eosinophils--with an accessory role for mast cells--monocytes and macrophages have been shown to exhibit cytotoxic properties against Schistosoma mansoni larvae, in association with antibodies of various isotypes or with complement (reviewed in ref. 1). Lymphocyte participation in effector functions is mediated mainly through lymphokines inducing cytotoxic macrophages, and, in certain cases, directly by T cells. The experiments reported here show that platelets, taken from rats after specific periods of infection with S. mansoni, were able to kill schistosomula, and that normal human or rat platelets acquired toxic properties towards the same target in the presence of serum from infected individuals. The humoral factor involved in this process was shown to be IgE, and evidence was obtained of a Fc receptor for IgE on human and rat platelets. The passive transfer of immune platelets to normal rats conferred a high degree of protection towards a challenge infection by the parasite.

Animals↗
PubMed1983

Characterization and synthesis of a macrophage inhibitory peptide from the second constant domain of human immunoglobulin G.

We have shown that IgG hydrolysed by Schistosoma mansoni schistosomula inhibited various macrophage functions, especially phagocytosis and anti-schistosome cytotoxicity. Here we show that a tripeptide, Thr289-Lys-Pro291, of the second constant domain of human immunoglobulin G (peptide 286-292) reproduced the inhibitory effect of a total hydrolysate. Indeed the beta-glucuronidase release from IgE-anti-IgE-stimulated rat and human macrophages decreased and its intracellular level did not rise after a prior incubation of the cells with Thr-Lys-Pro (500 nmol/ml). Moreover, the cell migration as well as the superoxide anion O2 generation were 50-80% reduced by the tripeptide. These results suggest that a single peptide set may be responsible for the decrease of the macrophage functions at the early stage of the parasite infection in the mammalian host. The pharmacologic properties of this tripeptide are under investigation.

Animals↗