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Biomedical subjects

A Capron

Publications and source records attributed to A Capron.

At least 73 records · Page 4Linked to original sources
PubMed1994

Elevation of soluble CD23 in serum from patients with blood eosinophilia.

The levels of soluble CD23 (sCD23) were evaluated by a two-site immunoradiometric assay in the sera of 41 patients with eosinophilia-associated disorders and 20 normal subjects. We observed that, in the absence of treatment, sCD23 levels were elevated in patients with eosinophilia-associated Gleich's syndrome, IgA deficiency, T lymphoma or hypereosinophilic syndrome (HES), but not in patients with a parasitic infection. A significant reduction in the sCD23 levels was found after treatment, with a parallel decrease in eosinophil counts and in sCD25 levels, a marker of disease activity in HES. The lack of increase in membrane CD23+ B cells in eosinophilic patients together with the detection of sCD23 in eosinophil supernatants suggest that activated eosinophils present in eosinophilia-associated disorders can release soluble molecules cross-reacting with CD23. In conclusion, our results suggest that eosinophils themselves can represent one cellular source of sCD23. These findings are not only basic but also of clinical interest.

Adrenal Cortex Hormones↗
PubMed1994

Development of a vaccine strategy against human and bovine schistosomiasis. Background and update.

Two specific characteristics of schistosome infection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive hosts (unlike protozoan parasites) and a partial non-sterilizing immunity can have a marked effect on the incidence of pathology and on disease transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reduction in parasite burden is a sufficient goal for vaccine induced immunity. We originally showed that IgE antibodies played in experimental models a pivotal role for the development of protective immunity. These laboratory findings have now been confirmed in human populations. Following the molecular cloning and expression of a 28 kDa protein of Schistosoma mansoni and its identification as a glutathione-S-transferase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction in parasite burden, vaccination with Sm28 GST was recently shown to reduce significantly parasite fecundity and egg viability leading to a decrease in liver pathology. Whereas IgE antibodies were shown to be correlated with protection against infection, IgA antibodies have been identified as one of the factors affecting egg laying and viability. In human populations, a close association was found between IgA antibody production to Sm28 GST and the decrease of egg output. The use of appropriate monoclonal antibody probes made it possible to demonstrate that the inhibition of parasite fecundity following immunization was related to the inhibition of enzymatic activity of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

SCID-Hu mouse as a model for human lung HIV-1 infection.

HIV induces a multi-organ infection with a dual tropism for both lymphocytes and monocytes/macrophages. The lung is a target both for HIV infection and HIV-related opportunistic infections. The SCID mouse has provided the opportunity to develop a small animal model for HIV infection. However, HIV-1 infection of the human fetal thymus and liver (SCID Liv/Thy) implanted in these mice occurred only after direct intraimplant injection of HIV-1 and the resultant HIV-1 infection was restricted to the human thymus. Here we report that human foetal lung can develop in SCID Liv/Thy mice resulting in the development of normal human alveolar and bronchiolar lung compartments which can be productively infected with cell-free HIV-1 virus, leading to a systemic and bifocal infection. This SCID-Hu model should be useful for studying AIDS physiopathology, human viruses with lung tropism and for helping to define gene therapy protocols in lung human cells in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Synovial fibroblast-like cell transfection with the SV40 large T antigen induces a transformed phenotype and permits transient tumor formation in immunodeficient mice.

OBJECTIVE: To understand the intracellular signals leading to transformed-like growth of synovial fibroblast-like cells from patients with rheumatoid arthritis (RA). METHODS: Cell lines stably transfected with one or both of 2 complementary oncogenes, the SV40 large T antigen and the ras oncogene, were studied for phenotypic changes. RESULTS: Synovial fibroblast-like cells stably transfected with the SV40 large T antigen, but not the ras oncogene, showed high levels of growth factor independent proliferation, grew under anchorage independent conditions, expressed cathepsin L mRNA, and formed transient tumors in immunodeficient mice. Synovial fibroblast-like cells stably transfected with both oncogenes appeared phenotypically similar to synovial fibroblast-like cells transfected with the large T antigen alone. CONCLUSION: The SV40 large T antigen confers a phenotype on synovial fibroblast-like cells similar to that stimulated by growth factors, suggesting that it stimulates the same intracellular signalling pathway leading to cytokine induced, transformed synovial fibroblast-like cell growth. When injected into immunodeficient mice these transfected cells formed tumors characterized by rapid, transient growth, central necrosis, and neutrophil infiltration.

Animals↗
PubMed1994

[Eosinophil, beneficial or harmful: a cell entirely part of immune response].

The demonstration that human eosinophils could express various membrane receptors (for IgG, IgE, IgA; for complement; for cytokines; for chemotactic factors), for adhesion molecules (VLA4, LFAI, OKM1), as well as CD4 and class II MHC, has allowed to reconsider the role of eosinophils in immune response. Indeed, eosinophils can function as antigen presenting cells and can be infected by HIV. Studies on eosinophil mediators have revealed that eosinophils are not only the source of cytotoxic and proinflammatory mediators but can also release various cytokines and growth factors, including their own factors of differentiation (IL-3, GM-CSF and IL-5). The recent observation that eosinophils expressed IgE binding molecules belonging to different gene superfamilies (CD23, Mac2/epsilon BP and FceRI), as well as two different IgA receptors (Fc alpha R, and secretory component binding site), participating both in antiparasite immune defence and in inflammatory processes, reinforces the concept of the functional duality of eosinophils, specially in tissues.

Antibody Formation↗
PubMed1993

Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases.

Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.

Biopsy↗
PubMed1993

Cloning and characterisation of the gene encoding the 28-kDa glutathione S-transferase of Schistosoma mansoni.

The 28-kDa glutathione S-transferase (GST) of Schistosoma mansoni is considered a possible vaccine candidate for use against this medically important parasite. The gene encoding this molecule has been isolated from a lambda EMBL4 library by using the corresponding cDNA sequence as a probe. The gene contains four exons and is approximately 5.5 kb in length. Analysis of the 5' flanking region revealed the presence of a consensus AP-1 recognition site, 5'-TGACTCA, between nucleotides -231 and -225. Southern blot analysis suggested the presence of a single gene encoding the 28-kDa GST in the S. mansoni genome.

Amino Acid Sequence↗
PubMed1993

[Vaccine against bilharziasis. Strategies and perspectives].

Due to the determination of immunity acquisition mechanisms, a number of studies on experimental models and human populations has made it possible to devise a strategy of vaccination against schistosomiasis, a major worldwide parasitic disease affecting 200 million people. A schistosomial protein, identified as glutathione-S-transferase (SM28GST) has been cloned and expressed in various vectors. Immunization with the recumbent protein results in a significant reduction of the parasitic load, while the fertility of schistosoma and the viability of its eggs are markedly inhibited. Recent experiments performed in primates and bovines have shown that a more than 90% inhibition of the schistosoma's transmission potential can be induced by this vaccine. The important role played by IgA antibodies in the inhibition of the parasite's fertility has led to the development of an oral immunization strategy. In view of the results obtained, the availability, in the near future, of a vaccine protecting human beings against this scourge can be considered realistic.

Animals↗
PubMed1993

Schistosoma mansoni 28-kDa glutathione S-transferase and immunity against parasite fecundity and egg viability. Role of the amino- and carboxyl-terminal domains.

We have previously shown that a mAb that inhibits the enzymatic activity of the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm28 GST) also reduces female worm fecundity and egg viability in vivo and in vitro. By peptidic epitope mapping and an activity reconstitution assay, the carboxyl terminus (CT) amino acid residues 190-211 and to a lesser extent the truncated amino terminus (NT) residues 10-43 of the enzyme were identified as mAb recognition sites. Sera from rats immunized with the NT (10-43) and CT (190-211) peptides showed a partial inhibitory effect on Sm28 GST activity in a late phase (6 to 7 wk) but not in an early phase (2 to 4 wk) after immunization. Passive transfer of Sm28 GST-inhibiting anti-N- and C-terminal sera, but not of the noninhibitory sera, protected the infected mice by reducing tissue egg deposition and the ability of eggs to hatch. In active immunization experiments, the CT peptide significantly decreased the worm burden (37 to 40%) in mice as did the rSm28 GST (28 to 52%). In terms of tissue egg deposition and egg-hatching ability, immunization with both the NT and CT peptides reproduced the reduction observed after immunization with rSm28 GST. A constant reduction in egg numbers was noted in the small intestines and the livers of the immunized mice. A clear reduction in the ability of intestinal or hepatic eggs to hatch was observed. The results are discussed in terms of the conformational participation of the NT and CT of Sm28 in the expression of GST activity.

Amino Acid Sequence↗
PubMed1993

IgA antibodies to a protective antigen in human Schistosomiasis mansoni.

The specific IgA antibody responses to the protective recombinant Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST) Ag and to derived synthetic peptides have been evaluated before and 6 mo after chemotherapy in S. mansoni-infected patients from Kenya. These studies revealed a parallelism between the age-dependent evolution of IgA antibody levels to Sm28GST and to one synthetic peptide (115-131) and the acquisition of resistance to reinfection. Functional analysis revealed that IgA antibodies to Sm28GST displayed a potent neutralizing effect on the enzymatic properties of the molecule, and also markedly impaired schistosome fecundity, by limiting both the egg laying of mature worms and the hatching capacity of schistosome eggs into viable miracidia. These results suggest that, in addition to IgE, IgA antibodies might participate in the protective immune response against schistosomiasis.

Adolescent↗
PubMed1993

Human neutrophils express immunoglobulin E (IgE)-binding proteins (Mac-2/epsilon BP) of the S-type lectin family: role in IgE-dependent activation.

It has been suggested that neutrophils may be involved in the late-phase reaction of immunoglobulin E (IgE)-dependent hypersensitivity states. However, the identity of neutrophil-associated molecules inducing the release of mediators remains unclear. In this report, we demonstrate that human neutrophils from normal donors or from patients with inflammatory disorders could bind myeloma IgE proteins, especially after desialylation. Northern blot, immunoprecipitation, and flow cytometry analyses revealed that neutrophils did not express Fc epsilon RII/CD23, but rather Mac-2/epsilon binding protein (BP), belonging to the S-type lectin family. Similarly to IgA used as positive control, myeloma IgE proteins, as well as polyclonal IgE antibodies with or without antibody specificity, were both capable of inducing a neutrophil respiratory burst. Anti-Mac-2 but not anti-CD23 mAb strongly decreased the IgE-dependent activation of neutrophils, induced either by the specific antigen or by anti-IgE antibodies. These findings open new perspectives on the functional role of neutrophils in IgE-associated diseases including allergic states or parasitic infections.

Antigens, Differentiation↗
PubMed1993

Protective immunity induced in rat schistosomiasis by a single dose of the Sm28GST recombinant antigen: effector mechanisms involving IgE and IgA antibodies.

Rats immunized by a single dose of the recombinant Sm28GST antigen, using either aluminium hydroxide or Bacillus Calmette-Guérin adjuvant, were significantly protected (up to 59% reduction in worm burden) against a challenge infection with Schistosoma mansoni cercariae. A follow-up study of the humoral response revealed the presence of high levels of IgE and IgA antibodies together with specific IgG. Sera from once Sm28GST-immunized rats induced a cytotoxic response for schistosomula targets in the presence of normal rat eosinophils, similar to the one induced by sera from twice immunized rats. Depletion or competition studies indicated the participation of both IgE and IgA antibodies in eosinophil-dependent cytotoxicity mechanisms. These results suggest the existence, in immunized rats exhibiting protection against schistosomiasis, of an original effector mechanism implying eosinophils and IgA antibodies, together with documented effector mechanisms involving IgE and eosinophils. In addition, they raise questions concerning the role of IgA antibodies in schistosomiasis.

Adjuvants, Immunologic↗
PubMed1993

CD3-mediated apoptosis of human medullary thymocytes and activated peripheral T cells: respective roles of interleukin-1, interleukin-2, interferon-gamma and accessory cells.

Clonal deletion represents an important mechanism for the establishment of tolerance, by the elimination of autoreactive T cells. Deletion is accomplished by programmed cell death, termed apoptosis, induced by mobilization of the T cell receptor (TCR) on both thymocytes and mature T cells. The mechanism which drives T cells towards cell death or cell proliferation after TCR mobilization remains unclear. We show here that the mobilization of the CD3/TCR complex of both CD4+ and CD8+ single-positive medullary human thymocytes and human mature activated T cells, in the absence of accessory cells, leads to an activation-induced cell death process by apoptosis. In both cases, apoptosis was associated with interferon (IFN)-gamma gene expression and secretion in the absence of interleukin (IL)-2 gene expression; and the addition of anti-IFN-gamma antibody prevented cell death. Apoptosis could also be prevented by cyclosporin A (CsA) treatment and could be re-induced by the addition of IFN-gamma to CsA-treated cells. Addition of IL-2 had two different effects, it prevented apoptosis and also allowed proliferation in response to CD3 monoclonal antibody. Addition of IL-1, which induces IL-2 gene expression and secretion or addition of accessory cells, had the same preventive effect. These results suggest that the uncoupling of IFN-gamma and IL-2 gene expression following CD3/TCR mobilization initiates apoptosis of human T cells at several different stages during development and activation. We propose that co-signals provided by accessory cells allow a coupling of IL-2 gene and IFN-gamma gene expression, and that an essential role for IL-2 secretion in T cell activation involves the inhibition of a death program induced by IFN-gamma secretion.

Antigen-Presenting Cells↗
PubMed1993

IgE-binding molecules (Mac-2/epsilon BP) expressed by human eosinophils. Implication in IgE-dependent eosinophil cytotoxicity.

Macrophage cell-surface protein 2 (Mac-2), a galactose specific S-type lectin identified in inflammatory macrophages, presents a high degree of homology with the rat IgE-binding protein (epsilon BP). In the present study, we show by different experimental approaches that human eosinophils can express Mac-2/epsilon BP. Flow cytometry analysis revealed that a large proportion of eosinophilic patients expressing binding sites for IgE on their eosinophil membrane, were able to bind anti-Mac-2 monoclonal antibody (mAb). Northern blot performed with eosinophil RNA hybridized with the human Mac-2 or epsilon BP cDNA probes revealed that eosinophils presented a unique transcript at 1.2 kb. Immunoprecipitation of eosinophil extracts with anti-Mac-2 mAb revealed the presence of a molecule of 29 kDa corresponding to Mac-2 protein, as well as one additional molecule of 15 kDa, absent from control alveolar macrophages. The function of these molecules was investigated in a radiolabeled IgE binding assay. Anti-Mac-2 mAb as well as galactose and lactose saccharides significantly inhibited the binding of radiolabeled human myeloma IgE protein to eosinophils. Moreover, the dose-dependent inhibition by anti-Mac-2 mAb of IgE-dependent eosinophil-mediated cytotoxicity towards parasite targets indicated the role of these IgE-binding molecules in the function of human eosinophils. These results suggest that in addition to transmembrane receptors, lectin-type molecules can participate in the IgE-dependent effector function of eosinophils.

Animals↗
PubMed1993

Schistosoma mansoni: an enkephalinergic system that may participate in internal and host-parasite signaling.

The present study is concerned with an opioid system in the human trematode Schistosoma mansoni, both as part of the endogenous chemical messenger system and as a tool in the parasite reaction to the host(s). A high-affinity opioid binding site was characterized in membrane suspensions prepared from adult worms. Scatchard analysis revealed a single class of receptors with a dissociation constant of 1.8 nM and a Bmax of 24.9 pmol/g protein for (D-Ala2, Met5)-enkephalin (DAME). The displacement experiments demonstrated that the most potent ligands were beta-endorphin, DAME, and met-enkephalin. These characteristics and the effects of various ions on DAME affinity suggest that S. mansoni has a delta-like opioid receptor, as previously described in other invertebrates. A met-enkephalin-like peptide was also characterized in a miracidial extract. Radioimmunoassay, reverse-phase HPLC, and bioassay by induction of cell conformational changes of human polymorphonuclear leukocytes revealed that the parasite peptide is very similar to authentic met-enkephalin. A met-enkephalin-like peptide was also shown to be present in adult worms and in their incubation medium. Taken together, these observations demonstrate the existence of a complete opiate system in S. mansoni. We discuss its role in molecular signaling within the parasite and in host-parasite interactions.

Animals↗