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Biomedical subjects

A Capron

Publications and source records attributed to A Capron.

At least 757 records · Page 42Linked to original sources
PubMedDate not supplied

Human IgE in severe combined immunodeficiency mice reconstituted with peripheral blood mononuclear cells from Dermatophagoides pteronyssinus-sensitive patients.

We studied conditions of human IgE formation in severe combined immunodeficiency (SCID) mice engrafted with peripheral blood mononuclear cells (PBMCs) from allergic patients sensitive to Dermatophagoides pteronyssinus (D.pt.). With 10 x 10(6) PBMCs injected intraperitoneally, the hu-SCID mice developed an IgE response, but only if experimental animals were immunized with the related allergen. Two routes of immunization were tested: intraperitoneal and inhalation. In these experimental conditions (allergen given at day 14 after reconstitution), a significant rise in total serum IgE but also in specific anti-D.pt. IgE was observed. No human IgE could be detected within 3-4 weeks after immunization with an unrelated allergen. Similarly, when mice were engrafted with PBMCs from nonallergic donors, even after D.pt. administration, no significant increase of serum IgE was detectable, while an IgG response was regularly found. Thus SCID mice could represent a useful model to analyze IgE production as well as the conditions of immunization required to obtain an optimal response.

Administration, Inhalation↗
PubMedDate not supplied

Differentiation of eosinophils from cord blood cell precursors: kinetics of Fc epsilon RI and Fc epsilon RII expression.

Expression of Fc epsilonRI and Fc epsilonRII/CD23 was examined by immunocytochemistry and flow cytometry on eosinophils differentiated from human cord blood cells in the presence of human interleukin-3 (rhIL-3), granulocyte/macrophage colony stimulating factor (rhGM-CSF) and interleukin-5 (rhIL-5) and on blood eosinophils purified from normal donors or patients with idiopathic hypereosinophilic syndrome (HES). On cord blood derived eosinophils, Fc epsilonRI expression started at 1 week of culture and increased to reach a plateau at 3 weeks of culture. Fc epsilonRII/CD23 appeared slightly later, after 2 weeks of culture, and the percentage of Fc epsilonRII/CD23-positive eosinophilic cells increased and stayed in plateau. Fc epsilonRI expression on cord blood derived eosinophils was downregulated after culture with interleukin-2 (rhIL-2), interleukin-4 (rhIL-4), rhIL-5, interferon-alpha (rhIFN-alpha), interferon-gamma (rhIFN-gamma). In contrast, the expression of Fc epsilonRII/CD23 on cord blood derived eosinophilic cells was upregulated after culture with rhIL-4, rhIL-5 and rhIFN-gamma, and downregulated with rhIL-2 and rhIFN-alpha. Fc epsilonRI was expressed on about 30% normal donor eosinophils as well as on normodense eosinophils from HES patients but significantly decreased on hypodense eosinophils. In contrast, Fc epsilonRII/CD23, expressed on a very small proportion of normal donor eosinophils, increased from normodense to hypodense eosinophils. These results suggest that Fc epsilonRI on eosinophils might represent one differentiation antigen expressed relatively early, with decreased expression through maturation or activation, whereas Fc epsilonRII/CD23 might rather be considered as a marker of eosinophil activation.

Cell Differentiation↗
PubMedDate not supplied

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

Schistosomiasis is a chronic and debilitating parasitic disease that affects over 200 million people throughout the world and causes about 500,000 deaths annually. 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 been now confirmed in human populations. Following the molecular cloning and expression of a protein 28 kDa protein of Schistosoma mansoni and its identification as a glutathion 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Further studies on the circulating M antigen in human and experimental Schistosoma mansoni infections.

Circulating M antigen, previously described in urine from patients infected by Schistosoma mansoni, was shown in serum from infected patients, using human anti-M immune serum with immunodiffusion and immunoelectrophoretic analyses. This antigen was also shown to be present in the serum and urine from infected hamsters, in the urine from infected rabbits and in the serum from infected mice. Generally, it appeared on day 20 after infection. M antigen was specific for the genus Schistosoma and for the immature and adult worm stage. Its electrophoretic migration was cathodic. The molecular weight of urinary M antigen was around 45,000 daltons. The M antigen was thermostable, soluble in trichloroacetic acid, and contained no lipid component. It was hydrolyzed by protease, ribonuclease, amylase or neuraminidase, but was destroyed by sodium metaperiodate. All these properties betoken the polysaccharidic nature of M antigen.

Animals↗
PubMedDate not supplied

Synthetic vaccines and HIV-1 hypervariability: a "mixotope" approach.

The hypervariability of the gp120 envelope protein principal neutralizing domain, the V3 loop, represents a major problem in the design of vaccines against HIV-1. We have designed a mixed V3 loop peptide, termed "mixotope," obtained in a unique synthesis, and containing around 7.5 x 10(5) different sequences of 22 to 25 residues, organized around the conserved GPGR tetrapeptide. Free or coupled to a carrier protein, the "mixotope" induced in rabbits broadly specific antibodies, which recognized different individual V3 loop sequences, and the native gp120 protein. The "mixotope" approach may allow researchers to focus vaccine strategy against hypervariable functional epitopes of various pathogens.

AIDS Vaccines↗
PubMedDate not supplied

Induction of CD23, CD25 and CD4 expression on an eosinophilic cell line (EoL-3) by interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5).

The effects of IL-3, GM-CSF and IL-5 on the expression of CD23 (Fc epsilon RII), CD25 (IL-2R/p55) and CD4 on an eosinophilic cell line (EoL-3) were investigated by flow cytometry. A separate incubation with IL-3, GM-CSF or IL-5 alone, did not induce the expression of CD23, CD25, or CD4. However, a sequential incubation with IL-3 for 6 days, then with IL-3 and GM-CSF for the following 6 days, induced a significant expression of CD23 and CD25. After a further incubation for 6 days with IL-3, GM-CSF and IL-5, CD4 was then expressed, while CD23 and CD25 expression still increased. The kinetics of expression of CR3/CD11b were parallel to that of CD23, but the expression of the transferrin receptor (CD71) remained negative. Northern blot analysis revealed the presence of mRNA encoding CD23, CD25 and CD4 in EoL-3 stimulated by IL-3, GM-CSF and IL-5. Culture with GM-CSF induced the binding of radiolabeled IL-5 to EoL-3 cells, with an increased affinity after incubation with IL-3, GM-CSF and IL-5. These data indicate that IL-3, GM-CSF and IL-5, might be involved in the expression of functional markers on eosinophil membrane.

Adult↗
PubMedDate not supplied

Epitopic characterization and vaccinal potential of peptides derived from a major antigen of Schistosoma mansoni (Sm28 GST).

The P28 antigen of Schistosoma mansoni has been shown to induce protective immunity against schistomiasis in rodents and primates. The analysis of the primary structure of the P28 molecule using various predictive algorithms led to the synthesis of seven peptides which were used to localize the major T cell epitopes of the P28. Two of these synthetic peptides (amino acids 24-43 and 115-131) were found to contain major T cell sites of the P28 antigen. Indeed, both 24-43 and 115-131 peptides stimulate T lymphocytes from Fischer rats and Balb/c mice immunized with the recombinant P28. Moreover, these localized moieties are exposed to the host's immune system during natural S. mansoni infection since they activate T cell populations of infected rats, mice and chronically infected Kenyan children. A multiple antigen peptide containing eight copies of peptide (MAP 115-131) has been prepared and used as immunogen in rats, mice and baboons. In all these models, the MAP 115-131 induces both humoral and cellular responses towards the P28. Preimmunization with the MAP 115-131 before a challenge with the whole P28 molecule increases T cell proliferation and antibody production. The active immunization of rats with the MAP 115-131 before a challenge with the whole P28 molecule increases the T cell proliferation and the antibody production. The active immunization of rats with the MAP 115-131 before challenge infection with the parasite achieved significant protection.

Amino Acid Sequence↗
PubMedDate not supplied

Effect of rIFN-gamma and IL-2 treatments in mouse and nude rat infections with Toxoplasma gondii.

Mice and nude rats lethally infected with T. gondii and treated with recombinant rat interferon-gamma (rIFN-gamma) or recombinant human interleukin-2 (rIL-2) were protected against death, when compared with untreated infected controls. In mice rIFN-gamma and rIL-2 played an important role in "prophylactic treatment", but not in "curative therapy". The survival rate was 42% in mice treated with 3 doses of 20,000 U of rIFN-gamma at days -2, -1, 0 before challenge and up to 66% in mice treated with 3 doses of 10,000 U of rIFN-gamma at days -2, 0, +2 before and after infection. Whereas the survival rate was 33% in mice that received 3 doses of 500 U rIL-2 at days -2, -1, 0 before infection, or -2, 0, +2 before and after infection respectively, up to 50% of the mice treated with 3 doses of 1,000 U rIL-2 at days -2, -1, 0 survived. In nude rats rIFN-gamma had a slight effect in "prophylactic treatment", whereas rIL-2 was active only in "curative treatment". The survival rate was 25% both in nude rats treated with doses of 400,000 U of rIFN-gamma at days -3, 0 before challenge, or with doses of 5,000 U of rIL-2 at days +2, +6, +9 after infection. These results lead us to hypothesise that the mechanism by which the lymphokine treatment exerts a protective effect on Toxoplasma infected mice is different from that on nu/nu rats. We conclude that these cytokines may play a notable role in modulating the host's immune defence against T. gondii infection.

Animals↗
PubMedDate not supplied

Introduction of Pneumocystis carinii in a colony of SCID mice.

Pneumocystis carinii-free SCID mice were housed closely exposed to corticosteroid-treated non-SCID mice in a conventional area of our laboratory animal facilities. A one-day exposure was sufficient for P. carinii transmission. The lung infection increased thereafter. Irradiation or splenectomy of SCID mice at the beginning of the exposure resulted in a marked increase of parasite multiplication. Extrapulmonary foci of pneumocystosis were detected in heart and spleen of SCID mice infected by P. carinii via air transmission.

Animals↗
PubMedDate not supplied

Interleukin-6 is the main mediator of the interaction between monocytes and platelets in the killing of Schistosoma mansoni.

We demonstrate the existence of a cooperation between monocytes and platelets for the killing of Schistosoma mansoni. Indeed, supernatants obtained after a 24 hr adherence of normal human monocytes were able to induce, in a dose dependent manner, the cytotoxicity of normal human platelets towards the young larvae of S.mansoni in vitro. The physicochemical analysis of the supernatants showed that a factor exhibiting a pl of 4.8-4.9 was responsible of this effect, suggesting a role of IL-6, detected in the supernatants, in this induction. This was confirmed by the neutralization of the cytotoxic effect by a polyclonal serum against IL6 whereas polyclonal sera against IL-1 beta or TNF-alpha, the other cytokines present in the supernatants, did not modify the cytotoxicity observed. Finally human recombinant IL-6 induces the platelet cytotoxic function, demonstrating a direct effect of IL6 on blood platelets.

Animals↗
PubMedDate not supplied

Antigenic release of paf-acether and beta-glucuronidase from alveolar macrophages of asthmatics.

Alveolar macrophages (AM) from control (n = 12) and atopic patients (n = 19, 12 without treatment, 4 treated with theophylline and 3 with theophylline and corticosteroid) were compared for their capacity to release mediators. AM were purified by 2 h adherence and challenged with either ubiquitous allergen, specific sensitizing allergens, anti-IgG or anti-IgE serum. The release of paf-acether, lyso paf-acether and beta-glucuronidase was measured. Paf-acether and its lyso derivative were assayed on washed rabbit platelets. Enzyme and mediator releases were obtained after specific allergenic or anti-IgE serum challenge of AM from untreated atopic patients. No release of paf-acether was detected from AM, from control or treated atopic patients after in vitro immunological challenge, whereas that of lyso paf-acether was greatly reduced in both treated groups. Release was obtained by immunological challenge of AM from control patients after passive sensitization with atopic serum. The release of mediators with bronchoconstriction activity by AM could represent an alternative causal pathway in human asthma.

Adult↗
PubMedDate not supplied

[Fibronectins: structure and function].

Fibronectins are a class of high-molecular-weight glycoproteins found in a soluble form in blood and other body fluids and in an insoluble form in tissues. Cellular and plasma fibronectins are very similar in structure and properties, but are not identical. Fibronectins are synthesized by a wide variety of cells in vitro including fibroblasts, Schwann cells, chondrocytes, myoblasts, macrophages, hepatocytes and intestinal epithelial cells. They exhibit an affinity for both native and denatured forms of collagen, fibrinogen or fibrin, glycosaminoglycans, proteoglycans and surfaces of many kinds of eukaryotic cells. Fibronectins also bind to bacteria, viral glycoproteins and some protozoan parasites and interact with complement components. As a result of these multiple interactions, fibronectins might act as a non-specific opsonin. Fibronectins have been implicated in a variety of cell functions including cellular adhesion and morphology, cytoskeletal organization, oncogenic transformation, cell migration, phagocytosis, haemostasis and embryonic differentiation.

Animals↗