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Biomedical subjects

A Capron

Publications and source records attributed to A Capron.

At least 235 records · Page 13Linked to original sources
PubMed1992

Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation.

We have previously demonstrated the production of tumor necrosis factor alpha (TNF) and interleukin-6 (IL-6) by alveolar macrophages (AM) from allergic asthmatics developing a late asthmatic reaction after bronchial allergen challenge. In order to explain the modalities of this monokine synthesis, we tested in vitro the effect of an IgE-dependent stimulation on blood monocytes (BM) and AM from control and asthmatic subjects. TNF and IL-6 secretions were evaluated in 24-h supernatants by radioimmunoassay and by the 7TD1 cell proliferation test, respectively. AM from allergic asthmatics secreted spontaneously higher concentrations of TNF and IL-6 than did BM or AM from control subjects. BM from asthmatics also produced spontaneously increased levels of TNF, but at a lesser degree than did AM. The addition of anti-IgE induced a significant increase of TNF and IL-6 secretions by mononuclear phagocytes from control subjects only after previous sensitization with IgE-rich medium. In contrast, the direct stimulation by allergen or anti-IgE of AM and BM from asthmatics enhanced significantly the production of TNF and IL-6 when compared with cells cultured in medium alone. In these conditions, IgE-dependent activation of cells from allergic asthmatics compared with those from control subjects increased monokine production in a similar manner. Costimulation by recombinant human interferon gamma and IgE-dependent triggering had a synergistic effect on TNF production, but it had only an additive action on IL-6 synthesis (respective increase index: 9.8 compared with 2.9 and 9.8 compared with 2.1, respectively, for BM from control and asthmatic subjects).(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗
PubMed1992

Diagnostic value of a synthetic peptide derived from Echinococcus granulosus recombinant protein.

A specific monoclonal antibody (MAb; EG 02 154/12) directed against a protein epitope of Echinococcus granulosus antigen 5 was used to screen a cDNA library constructed from E. granulosus protoscoleces RNA. One clone designated Eg14 was selected and shown to code for an amino acid sequence partially homologous to that of the clone Eg6 previously identified with the same MAb. Hydrophobic cluster analysis showed that both recombinant antigens may adopt a similar alpha-helical organization and share a common conformational epitope. A synthetic peptide (89-122) mimicking the conformational site of Eg6 and Eg14 was constructed and demonstrated to be able to inhibit binding of the MAb and human hydatid sera to the Eg6 fusion protein (FP6) or to native hydatid antigens. To assess the diagnostic value of the peptide 89-122, we tested sera from patients infected with different parasites for their antibody reactivity with this peptide in ELISA. A high binding sensitivity and specificity of IgG-A-M antibodies were obtained with E. granulosus-infected patient sera. Moreover, the peptide 89-122 was found to be specifically recognized by IgE antibodies from patients with hydatid disease. These results indicate the particular interest of this synthetic peptide as a standardized antigen in diagnosis and treatment surveillance of hydatidosis.

Amino Acid Sequence↗
PubMed1992

Vaccine strategies against schistosomiasis.

In this review the authors analyze the effector and regulatory mechanisms in the immune response to schistosomiasis. To study these mechanisms two animal models were used, mouse and rat. The mouse totally permissive host like human, show prominent-T cell control in the acquisition of resistance. But other mechanisms like antibody mediated cytotoxicity (ADCC) involving eosinophils and IgG antibodies described in humans, are observed in rats. Also in this animal, it is observed specific IgE antibody high production and blood and tissue eosinophilia. Using the rat model and schistosomula as target, some ADCC features have emerged: the cellular population involved are bone marrow derived inflammatory cell (mononuclear phagocytes, eosinophils and platelets), interacting with IgE through IgE Fc receptors. Immunization has been attempted using the recombinant protein Sm28/GST. Protection has been observed in rodents with significant decrease of parasite fecundity and egg viability affecting the number, size and volume of liver egg granulomas. The association of praziquantel and immunization with Sm28/GST increases the resistance to infection and decreases egg viability. The authors suggest the possibility of the establishment of a future vaccine against Schistosoma mansoni.

Animals↗
PubMed1992

Effector functions of eosinophils in schistosomiasis.

The dual function of eosinophils is clearly illustrated in schistosomiasis. Well equipped in membrane receptors for immunoglobulins and complement, and due to the presence of granule basic proteins, eosinophils can become cytotoxic for parasite larvae and thus participate to protective immunity. However, mediators can also exert their cytolytic effect on normal cells or tissues, inducing therefore pathology. through ADCC mechanisms against schistosome larvae in vitro involving different antibody isotypes (IgG, IgE and IgA) and also in experiments performed in vivo, eosinophils have been clearly involved in protective immunity. Although no direct evidence of the protective role of eosinophils were brought in humans, the striking association of eosinophil-dependent cytotoxic antibody isotypes with resistance to reinfection (for instance IgE and IgA antibodies), whereas in vitro blocking antibody isotypes (IgG4, IgM) were detected in susceptible subjects, strongly, suggested the participation of eosinophils in antibody-dependent protective immune response. However eosinophils could also participate to granuloma formation around S. mansoni eggs and consequently to the pathological reactions induced by schistosomiasis.

Animals↗
PubMed1992

Vaccine strategies against schistosomiasis.

Schistosomiasis, the second major parasitic disease in the world after malaria affects at least 200 million people, 500 million being exposed to the risk of infection. It is widely agreed that a vaccine strategy which could lead to the induction of effector mechanisms reducing the level of reinfection and ideally parasite fecundity would deeply affect the incidence of pathological manifestations as well as the parasite transmission potentialities. Extensive studies performed in the rat model have allowed the identification of novel effector mechanisms involving IgE antibodies and various inflammatory cell populations (eosinophils, macrophages and platelets) whereas regulation of immune response by blocking antibodies has been evidenced. Recent epidemiological studies have now entirely confirmed in human populations the role of IgE antibodies in the acquisition of resistance and the association of IgG4 blocking antibodies with increased susceptibility. On the basis of these concepts, several schistosome target proteins have been identified and their encoding genes cloned. One of them, a schistosome glutathione S-transferase (Sm 28 GST) appears as a promising vaccine candidate. Immunization experiments have shown that two complementary goals can be achieved: (a) a partial but significant reduction of the worm population (up to 60% in rats); (b) a significant reduction of parasite fecundity (up to 70% in mice and 85% in cattle) and egg viability (up to 80%). At least two distinct immunological mechanisms account for these two effects. IgE antibodies appear as a major humoral component of acquired resistance whereas IgA antibodies appear as a major humoral factor affecting parasite fecundity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The interleukin 2 receptor in the hypereosinophilic syndrome.

The hypereosinophilic syndrome (HES) has been previously described as a clinicobiological entity characterized by a blood eosinophil count of over 1.5 x 10(9)/L of unknown cause associated with several clinical complications. In reality, HES is a heterogeneous group of diseases with variable and unpredictable progress in visceral lesions, thought to be related to the deleterious effects of tissue eosinophil infiltration. Various criteria for discrimination between benign and severe forms of HES have been described. These previous retrospective clinical investigations, using biological and clinical markers, have defined different stages of HES. It appears more relevant, however, to consider elements of disease activity by studying mechanisms of induction of persistent hypereosinophilia. The T-cell dependence of blood eosinophilia has led us to evaluate various markers of T-cell activation in particular. In the present review, we report previous results and perspectives suggested by the study of the interleukin 2 receptor in HES.

Biomarkers↗
PubMed1992

Fibronectin cleavage fragments provide a growth factor-like activity for the differentiation of Trypanosoma cruzi trypomastigotes to amastigotes.

The morphological and biochemical events following Trypanosoma cruzi trypomastigote-fibronectin (Fn) interactions have been studied. Adhesion of trypomastigotes to Fn-coated surfaces is followed by Fn degradation. The proteolytic cleavage of Fn was demonstrated by qualitative and quantitative measurement of Fn degradation after its exposure to trypomastigotes as well as polyacrylamide gel analysis of Fn proteolysis by a parasite protease (s). The released Fn peptide fragments stimulated the transformation of trypomastigotes to amastigotes. The gelatin (45 kDa) and heparin (40 kDa) binding fragments were shown to be able to promote trypomastigote differentiation. In contrast, native Fn and the 120 kDa fragment (cell attachment domain) were inactive. Complementary investigations showed that the gelatin and heparin binding fragments stimulated parasite RNA synthesis and protein synthesis and phosphorylation but not DNA replication and increased parasite intracellular cAMP concentrations. These findings suggest that the proteolysis of Fn by parasite proteases, which occurs under physiological conditions, might facilitate invasion of target cells by trypomastigotes. The Fn peptides released during this process may act as "growth factor-like" substances.

Animals↗
PubMed1992

Proopiomelanocortin-derived peptides as tools of immune evasion for the human trematode Schistosoma mansoni.

Schistosomes are digenetic trematodes which share their life cycle between a definitive (vertebrate) and an intermediate (invertebrate) host. Their survival is highly dependent on their ability to reduce significantly the efficiency of the host defences. We have previously demonstrated the presence of POMC derived peptides (ACTH, alpha-MSH, beta-endorphin) in all stages of Schistosoma mansoni life cycle. Given the immunomodulatory properties of these peptides in vertebrates and invertebrates it has been postulated that they might be implicated in parasite immune evasion. We report the release of these neuropeptides during the cycle, associated with the inhibition by these peptides of the locomotory activity of immunocytes from both hosts, the hamster Mesocricetus auratus and the freshwater snail B. glabrata. The implication of these common signals in this new strategy of parasite adaptation is discussed.

Animals↗
PubMed1992

[Programmed death (apoptosis) of T CD4 lymphocytes and AIDS pathogenesis].

A major characteristic of human immunodeficiency virus (HIV) infection is progressive decline in T CD4+ lymphocytes. Ten years after infection, on average, this cell subpopulation disappears and AIDS develops. In the asymptotic phase T CD4+ lymphocytes no longer respond, in vitro or in vivo, to certain memory antigens constrained by the class II histocompatibility complex, or in vitro to polyclonal activators like pokeweed mitogen. They retain, however, some proliferative response activity and constitute only a small proportion of the T CD4+ population. Indirect mechanisms of depletion are therefore sought. We have proposed a hypothesis for a single mechanism: a programmed death process, apoptosis, reactivated in mature T CD4+ lymphocytes of seropositives. Unlike necrosis, apoptosis has a role in embryogenesis, in the adult in certain cell populations and, in immature thymocytes, in T lymphocyte selection and establishment of self-tolerance. T CD4+ lymphocytes of infected subjects lose their ability to proliferate in vitro, as they undergo a form of suicide in response to certain stimuli. In vivo T CD4+ cell activation induced by various infectious agents, including HIV, progressively reduces the subpopulation, independently of the virus' cytopathogenic effect. Tests were performed that explored the T CD4+ lymphocyte response to super-antigens, which mimic and amplify the effect of memory antigens by way of CMH II molecules of Ag-presenting cells and certain nu beta chains of the alpha beta receptor for the Ag which are expressed by a third of human mature T CD4+ lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

Functional analysis of a T cell line specific for antiidiotypic antibodies to a Schistosoma mansoni protective epitope. I. Role in the anti-S. mansoni antibody response.

Previous data have shown that from an antiparasitic IgE mAb (mAb1), antianti-Id IgG and IgE antibodies (Ab3) could be prepared. These Ab3 demonstrated the same functional properties as the Ab1, such as in vitro cytotoxic activity toward schistosomula and in vivo a protective effect against Schistosoma mansoni infection. To study the possible interactions between the idiotypic network and the regulation of isotypic expression, we focused on Id-specific T cells obtained by immunization with Ab2. Both Ab2 idiotopes and native schistosomula Ag were able to stimulate the proliferation of anti-Ab2 T cells in vitro. The activation of anti-Ab2 T cells by Ab2 shared the classic characteristics of Th cells, namely, it was MHC-restricted and required APC. A T cell line could be maintained in long term culture by stimulation with schistosomula Ag. The adoptive transfer of cells from this line to 26-kDa Ag-immunized or S. mansoni-infected rats led to a dramatic increase in the specific humoral response. This effect was restricted to antibodies specific for 26- and 56-kDa Ag (the targets of the mAb1) and was observed for the two isotypes tested, i.e., IgG and IgE. Finally, the helper effect on the antibody response could be further amplified by cooperation of anti-Ab2 T cells with Id-specific cells of the first generation (anti-Ab1 cells). Together with Ag-specific Th cells, the Id-specific T cells may, due to their specificity and their functional properties, play a major role in the induction and more importantly, in the maintenance of the immune response.

Animals↗
PubMed1991

Functional analysis of a T cell line specific for antiidiotypic antibodies to a Schistosoma mansoni protective epitope. II. Induction of protective immunity in experimental rat schistosomiasis.

In our previous work on the idiotypic network in the rat model of schistosomiasis we showed that immunization with an IgE mAb specific for 26/56-kDa parasitic Ag resulted in the production of anti-anti-Id antibodies of both the IgG and IgE classes. Further studies demonstrated that anti-Ab2 T cell lines, obtained by immunization with Ab2 antibodies, functioned as conventional Th cells; they were MHC-restricted and required APC to proliferate in the presence of the native schistosomula Ag and the Ab2 antibodies. We report the involvement of these anti-Ab2 cells in the regulation of protective immunity. The transfer of long term culture anti-Ab2 T cell lines into LOU/M rats, followed by a challenge infection by Schistosoma mansoni 1 day after the cell transfer led to a slight increase in the worm burden. On the contrary, the transfer of anti-Ab2 T cells 90 days before S. mansoni infection induced a significant reduction of the worm burden (up to 57%). T cells recovered from the protected rats were stimulated by the native schistosomula Ag as well as by tryptic fragments of IgG isolated from the Ab2 sera, in the presence of irradiated thymic cells as APC. We also analyzed the humoral response developed by the rats after transfer with the anti-Ab2 T cell lines. The sera induced various inflammatory cells into cytotoxic effectors against the larvae of S. mansoni, arguing for the presence of functional IgE in the sera. Moreover, when these sera were passively transferred into rats infected 1 day later, a significant reduction of the worm burden was observed. However, antibody-dependent cytotoxic mechanisms efficient 10 days after the anti-Ab2 T cell transfer did not correlate with the protective immunity which required a 90-day delay to be established. These data suggest that the protective immunity induced by the anti-Ab2 cells is supported both by the cellular and humoral components and that in a future vaccinating strategy the idiotypic network may play a crucial role.

Animals↗
PubMed1991

Identification and characterization of a functional receptor for interferon-gamma on a megakaryocytic cell line.

We have previously shown that human interferon-gamma (Hu-IFN-gamma) induces platelets to become efficient effector cells, capable of killing young larvae of the parasite Schistosoma mansoni. Recently, binding sites for IFN-gamma on platelets have been characterized. We show here the presence of high-affinity receptors for IFN-gamma on the surface of the human megakaryocytic Dami cell line. Scatchard analysis indicated the presence of about 11,000 binding sites per cell, with a kd of 3 +/- 0.5 x 10(-10) mol/L; the apparent molecular weight of the receptor was 90 Kd. Receptor-bound 125I Hu-recombinant IFN-gamma was rapidly internalized and degraded when the temperature was increased from 4 degrees C to 37 degrees C. The half-life of this receptor was about 7 hours, and pretreatment of cells with IFN-gamma or phorbol myristate acetate had very little effect on the surface receptor number and no detectable effect on IFN-gamma receptor messenger RNA (mRNA) expression. The receptor was functional, because 24 hours of treatment with IFN-gamma led to the increase of HLA class I mRNA expression and to the initiation of HLA class II mRNA expression. These effects were selective because platelet glycoprotein Ib, IIb, or IIIa mRNA expression and cell proliferation were unaffected.

Blotting, Northern↗
PubMed1991

Improved permeabilization procedure for flow cytometric detection of internal antigens. Analysis of interleukin-2 production.

A cell membrane permeabilizing treatment is described which involves the use of lysolecithin at low concentration in acidic acetate buffer and paraformaldehyde fixation. It preserved well-separated scatter cytograms of small and large lymphocytes. The accuracy of the immunochemical detection of internal antigens by flow cytofluorography was demonstrated by the linear relationship between the percentage of fluorescent cells detected and the proportion of intracellular antigen-containing cells in mixtures with antigen-negative cell lines. Cell cycle analysis by dual nuclear staining with propidium iodide and FITC-conjugated Ki-67 antibody recognising in vitro stimulated human T lymphocytes verified that the proliferating lymphocytes retained their increased light scatter properties after permeabilization. Enumeration of interleukin-2 (IL-2) producing cells by their cytoplasmic immunofluorescence showed that enlarged lymphocytes were the main IL-2 producing cells. This improved permeabilization procedure, by gating small and enlarged lymphocytes separately, makes it possible to determine by two color fluorescence the immunophenotype of activated T cells committed to interleukin production.

Cell Cycle↗
PubMed1991

Human eosinophils from hypereosinophilic patients spontaneously express the p55 but not the p75 interleukin 2 receptor subunit.

The expression of interleukin 2 receptor (IL2R) on eosinophils was investigated in patients with hypereosinophilia. Hypodense activated eosinophils have been described in various diseases such as parasitic or allergic diseases, hypereosinophilic syndrome (HES) associated in some cases to myeloproliferative markers, and more recently described in patients undergoing recombinant IL2 treatment. The presence of p55 alpha chain of IL2R (CD25) on purified eosinophils collected from blood of hypereosinophilic patients was detected by flow cytometry. In 10 out of 19 cases, more than 10% of eosinophils were CD25+. Cross-linking studies on enriched eosinophils showed one 64-75-kDa band, consisting of IL2 (15 kDa) cross-linked to the IL2R p55 subunit. In Northern blot analysis the two messenger mRNA (3.5 and 1.5 kb) encoding the IL2R p55 subunit were identified after hybridization with a CD25 cDNA probe. In contrast, the presence of the IL2R p75 subunit was not detected. These data provide preliminary evidence for the expression of a low-affinity receptor for IL2 on in vivo activated eosinophils and raise the question of the role played by this cytokine in eosinophil differentiation and activation.

Eosinophilia↗
PubMed1991

Obtention of a human primary humoral response against schistosome protective antigens in severe combined immunodeficiency mice after the transfer of human peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMC) from healthy donors were injected into C.B.-17 severe combined immunodeficiency (scid) mice which were subsequently immunized with crude Schistosoma mansoni adult worm antigenic preparation (SWAP) or with recombinant S. mansoni 28-kDa glutathione transferase (r-Sm-28-GST) antigen. PBMC from a S. mansoni-infected patient were also transferred. The specific human anti-SWAP and anti-Sm-28-GST antibody responses were monitored. The presence in both cases of human specific antibodies in scid mouse sera was determined by enzyme-linked immunosorbent assay and Western blotting techniques using anti-human immunoglobulin reagents. No antibodies were detected in these sera using anti-mouse immunoglobulin antisera. These antibodies were functional since a cytotoxic activity against schistosomula was observed when monocytes were incubated with scid mouse sera positive for anti-Sm-28-GST antibodies.

Animals↗
PubMed1991

A monoclonal antibody blocking the Schistosoma mansoni 28-kDa glutathione S-transferase activity reduces female worm fecundity and egg viability.

The protective effects of two different monoclonal antibodies (mAb) raised against the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm 28 GST) were investigated. Two mAb of the same isotype (IgM) have been selected according to the blocking effect on Sm 28 GST enzymatic activity (S13) or the lack of blockade (H12). When passively transferred into Fischer rats, both S13 and H12 significantly reduced the worm burden. In BALB/c mice clear effects on female worm fecundity and egg viability were observed when the S13 mAb was transferred; these effects included significantly reduced loads of intestinal eggs, reduced egg hatching rates and an increased proportion of non-living eggs. No effect on egg production and egg hatching was observed in H12-treated mice. In addition, worm pairs recovered from S13-but not H12-treated mice laid significantly fewer eggs in vitro, and normal worm pairs incubated in vitro with the S13 mAb produced significantly fewer eggs than those incubated with H12 mAb. The impairment of egg hatching ability was also reproduced in vitro by the S13 mAb. These data suggest the existence of two different effector mechanisms induced by immunization with Sm 28 GST. The effect on the schistosome worm burden appears to be independent of GST activity whereas the effect on S. mansoni female fecundity and egg viability seems to be significantly linked to the inactivation of the enzymatic site.

Animals↗