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Biomedical subjects

A Capron

Publications and source records attributed to A Capron.

At least 739 records · Page 41Linked to original sources
PubMedDate not supplied

Dose-dependent systemic human immunodeficiency virus infection of SCID-hu mice after intraperitoneal virus injection.

SCID mice were engrafted with human foetal liver, thymus and lung. Human cells were subsequently detected among peripheral blood leukocytes for 81% of tested animals and in tissue implants for 100% of tested animals. SCID-hu mice received intraperitoneal injections of human immunodeficiency virus type 1 (HIV1) at from 20 up to 20,000 median tissue culture infectious doses (TCID5). HIV1 infection was detected by means of cell culture and polymerase chain reaction both in blood and implants, up to 58 days after infection. The rate of infection was dependent upon the inoculated dose: the frequency of thymus infection ranged from 14% with 20-500 TCID50 up to 100% with 20,000 TCID50. HIV1 infection was detected less frequently in blood leukocytes than in thymus. Thymus virus load ranged from 40 to 50,000 HIV1 provirus copies per million cells and was not correlated with either infectious dose or viraemia. Thymus T-cell depletion was observed mainly in the CD1+4+8+ immature thymocyte compartment. The same rate of SCID-hu mouse infection was obtained using three different primary HIV1 isolates, suggesting that infection was not restricted to a few particular virus strains. The systemic infection of SCID-hu mice following intraperitoneal virus injection mimics some traits of human HIV infection and provides a promising, novel approach for future investigations in this field.

Animals↗
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Malaria co-infection in children influences antibody response to schistosome antigens and inflammatory markers associated with morbidity.

The epidemiological coexistence of schistosomiasis and malaria is frequently observed in developing countries. Co-infection with malaria in children could influence the development of acquired immunity associated with the resistance or the pathology of schistosomiasis. In the present study, performed during May to June 1996 in Senegal, the humoral immune response to Schistosoma haematobium 28 kDa glutathione S-transferase (Sh28GST) vaccinal antigen and to soluble egg antigens (SEA) has been evaluated in individuals infected by S. haematobium. Specific immunoglobulin G3 (IgG3) and IgE responses were significantly higher in co-infected children with Plasmodium falciparum compared with children infected with S. haematobium only. In addition, circulating levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble tumor necrosis factor receptor II (sTNF-RII), 3 parameters associated with schistosomiasis morbidity, were significantly increased in co-infected children. Taken together, this study indicated that malaria co-infection can both influence the acquired specific immune response to schistosome antigens and unbalance the regulation of inflammatory factors closely involved in schistosomiasis pathology.

Adolescent↗
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Specific IgE antibodies to Leishmania braziliensis in patients with mucocutaneous leishmaniasis.

A total of 116 sera of patients suffering from South American mucocutaneous leishmaniasis were analysed using the RAST (L. braziliensis-specific) and RIST techniques. Results of total and specific IgE levels were correlated with different clinical stages of the disease. The level of total and specific IgE appeared to be higher among patients with cutaneous ulcers than among those presenting mucocutaneous lesions, i.e. espundia. Furthermore, non-treated patients presented higher concentrations of total and specific IgE than did treated ones.

Antibody Specificity↗
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The effector function of platelets is induced and regulated by T lymphocytes.

The demonstration of effector functions of platelets in parasitic diseases raised the question of their possible regulation by T lymphocytes. Normal human platelets, treated with culture supernatants from antigen- or mitogen-stimulated CD4+/CD8- T cells, developed the capacity to kill young larvae of Schistosoma mansoni, in the absence of antibodies. The presence of IFN gamma in the lymphocyte supernatants, the neutralization by monoclonal anti-IFN gamma antibody, and the direct inducer effect of recombinant IFN gamma, clearly identify this lymphokine as one of the stimulator factors. In contrast, ConA- and antigen-stimulated human CD8+/CD4- T-cell supernatants contained a factor able to inhibit the IgE-dependent platelet cytotoxicity toward the same targets. The production of oxygen metabolites by IgE-coated platelets stimulated by anti-IgE was also strongly inhibited by this lymphokine. This platelet activity suppressive lymphokine (PASL) was identified as a polypeptide of 15 to 20 Kd with a pI of 4.6. The in vivo relevance of PASL was demonstrated by the complete abolition, after PASL treatment, of the protection normally conferred following a challenge infection by intravenous passive transfer of platelets from immune to normal rats.

Adult↗
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Fibronectin receptors on Trypanosoma cruzi trypomastigotes and their biological function.

Successful invasion of mammalian cells by pathogenic parasites is generally considered, from circumstantial evidence, to be a consequence of specific mechanisms of recognition of cell surface components--this has stimulated investigations of the biochemical characterization of such molecules. Several studied of trypanosomiasis have examined the ability of parasites to interact with mammalian cells. However, knowledge of the mammalian cell surface 'receptors' which interact with the parasite is limited. We now report that fibronectin, which is a high molecular weight glycoprotein present in blood, connective tissue and at cell surfaces, binds specifically to Trypanosoma cruzi trypomastigotes. The reaction is specific, reversible (in the presence of a 100-fold molar excess of unlabelled ligand) and of moderate affinity (Kd = 11.36 nM). Various other proteins (for example, thyroglobulin, ferritin, catalase, aldolase, human IgG and bovine serum albumin) had no significant effect on the binding of labelled ligand to the parasite surface. Addition of anti-fibronectin antibodies to the culture medium significantly inhibited the infection of rat fibroblasts (3T3 FR) by T. cruzi trypomastigotes, suggesting that cell surface fibronectin may act as a recognition site for attachment of the parasites.

Animals↗
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An anti-idiotype vaccine against experimental schistosomiasis.

Schistosomiasis is a parasitic infection of man which is widespread in tropical countries, and which so far has resisted attempts at control. We have been approaching the problem from an immunological angle. We have previously reported the production of a rat monoclonal IgG2a antibody against Schistosoma mansoni which exhibits marked cytoxicity for schistosomula in the presence of eosinophils and a high degree of protection by passive transfer in naive rats. This antibody, IPLSm1, was shown to bind specifically to a schistosomulum membrane target antigen defined as a glycoprotein of relative molecular mass 38,000 (38K), which is strongly immunogenic in schistosome infection of various animal species including man. Although theoretically the 38K protein represents an excellent candidate for a potential vaccine against schistosomiasis, the glycanic nature of the epitope recognized by IPLSm1 limits its production by DNA recombinant technology. It was, moreover, shown that, together with protective antibodies, the 38K molecule was able to induce the production of blocking IgG2c antibodies that inhibit the functional properties of IPLSm1 both in vitro and in vivo. Therefore, following Jerne's network theory, we considered an alternative approach, the possibility of immunization using anti-idiotype antibodies. In the present study, rat monoclonal anti-idiotype antibodies were produced against IPLSm1 (AB1). Anti-idiotype antibodies (AB2) were selected by their capacity to inhibit the binding of radioiodinated AB1 to its 38K target antigen. Sera from naive LOU rats immunized with a purified AB2 preparation contained specific anti-schistosome antibodies (AB3) which bound to 38K. AB3 antibodies were strongly cytotoxic for schistosomula in the presence of rat eosinophils and conferred highly significant protection by passive transfer. Most importantly, rats immunized with AB2 demonstrated marked protection (50-80%) to a challenge infection.

Animals↗
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Schistosoma mansoni shares a protective oligosaccharide epitope with freshwater and marine snails.

The expression of similar antigenic determinants by trematode parasites and their intermediate (invertebrate) or definitive (vertebrate) hosts has been previously reported. Studies of experimental and human infection by the parasite Schistosoma mansoni have revealed the strong immunogenicity of a surface antigen with a relative molecular mass (Mr) 38,000 (38K). Here we provide evidence that the important protective epitope of the 38K molecule is expressed by the uninfected intermediate host of S. mansoni, Biomphalaria glabrata and is synthesized both by the mollusc and by the parasite throughout its life cycle, thus confirming our original hypothesis. Deglycosylation experiments indicate that the protective epitope is an oligosaccharide and in B. glabrata, is associated with a 90K component. Analysis of soluble extracts from different freshwater mollusc species shows that the same protective epitope is found in schistosome as well as in non-schistosome hosts. Moreover, it was also found on the haemocyanin of the keyhole limpet (Megathura crenulata), a carrier protein widely used in immunological studies.

Animals↗
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Platelets mediate the action of diethylcarbamazine on microfilariae.

More than 400 million people in the world are infected by filarial parasites leading to a wide range of pathologies. Although introduced in 1947, the mainstay of the therapy and control of the filariases is diethylcarbamazine (N,N-diethyl-4-methyl-1-piperazine carboxamide; DEC), the mode of action of which still remains unknown despite widespread use and intensive laboratory investigations. The marked contrast between an extremely rapid action in vivo and the absence of any significant activity on microfilariae in vitro is unique among chemotherapeutic agents. DEC has been thought to modify the surface layer of the microfilariae and expose them to immunological cell-mediated lysis. This report provides the first evidence that the effect of DEC is mediated by blood platelets with the additional triggering of a filarial excretory antigen (FEA). The killing mechanism is antibody-independent and involves the participation of free radicals.

Animals↗
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Molecular cloning of a protective antigen of schistosomes.

The complementary DNA sequence encoding the Mr 28,000 antigen of Schistosoma mansoni has been isolated and expressed in Escherichia coli. Experimental vaccination of rats, hamsters and monkeys with a recombinant fusion protein induces a strongly cytotoxic antibody response. Immunization of rats and hamsters with this protein leads to significant protection against a natural challenge infection with live cercariae.

Amino Acid Sequence↗
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Schistosomiasis co-infection in humans influences inflammatory markers in uncomplicated Plasmodium falciparum malaria.

Malaria and schistosomiasis are the two major parasite diseases present in developing countries. The epidemiological co-infection with schistosomiasis could influence the development of the physiological reaction associated with Plasmodium falciparum infection in human. Most studies have demonstrated the association of circulating levels of interferon-gamma (IFN-gamma), tumour necrosis factor-a (TNF-alpha), interleukin-10 (IL-10), transforming growth factor (TGF-beta) and soluble Tumour Necrosis Factor Receptors (sTNF-RI and sTNF-RII) with the morbidity of malaria. In the present study, we showed that Schistosoma haematobium co-infection influences, in an age-dependent manner, the unbalance between pro- and anti-inflammatory circulating cytokines that play a key role during malaria infection. Indeed, children co-infected by S. haematobium have higher levels of IFN-gamma and sTNF-RII than children infected only by P. falciparum. In contrast, co-infected adults presented a significant increase of IFN-gamma, IL-10, TGF-beta, sTNF-RI and sTNF-RII rates and IL-10/TNF-alpha ratio. Taken together, this study indicates that schistosomiasis co-infection can unbalance the regulation of inflammatory factors in uncomplicated P. falciparum malaria. The possible consequences of the schistosomiasis co-infection for age-dependent malaria morbidity are discussed.

Adolescent↗
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Vaccine strategies against schistosomiasis: from concepts to clinical trials.

Schistosomiasis, the second major parasitic disease in the world after malaria, affects 200 million people. Vaccine strategies represent an essential component of the control of this chronic debilitating disease where the deposition of millions of eggs in the tissues is the main cause of pathology. Research developed in our laboratory over the last 20 years has led to the identification of novel effector mechanisms, pointing for the first time to the protective role of Th2 responses and of IgE antibodies now supported by seven studies in human populations. The identification and molecular cloning of a target antigen, a glutathione S-transferase (GST), has made it possible to demonstrate its vaccine potential in several animal species (rodents, cattle, primates) and to establish consistently the capacity of vaccination to reduce female worm fecundity and egg viability through the production of neutralizing antibodies (IgA and IgG). Following promising preclinical studies, clinical trials (phase I and II) have been undertaken using Schistosoma haematobium GST, Sh28GST. High titers of neutralizing antibodies were produced (IgG3 and IgA) together with Th2 cytokines, consistently with the concepts developed from experimental models. With these results we are on the way towards a feasible approach of vaccine development against a major human parasitic disease.

Animals↗
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Synthesis of cytokines by eosinophils and their regulation.

In addition to cytotoxic and proinflammatory mediators, eosinophils can produce a variety of cytokines and growth factors. Besides interleukin (IL)-5, we show in the present work that human eosinophils can synthesize interferon (IFN)-gamma and IL-10, by RT-PCR, in situ hybridization and immunostaining. Double-labelling procedures revealed the coexpression of IL-5 and IL-10 but not IL-5 and IFN-gamma, indicating the existence of subpopulations of eosinophils expressing type 1 or type 2 cytokines. IFN-alpha efficiently used for the treatment of hypereosinophilic syndromes can significantly decrease eosinophil degranulation and IL-5 release by eosinophils, through binding to a receptor for IFN-alpha. Thus, eosinophils can represent major sources of cytokines with regulatory functions, especially in allergic diseases and parasitic infections.

Cytokines↗