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Biomedical subjects

A Capron

Publications and source records attributed to A Capron.

At least 523 records · Page 29Linked to original sources

Heterogeneity of human peripheral blood eosinophils: variability in cell density and cytotoxic ability in relation to the level and the origin of hypereosinophilia.

Considerable variations in the distribution of eosinophil populations were revealed by density gradient centrifugation of peripheral blood leukocytes from 14 normal subjects and 31 patients with a transient or persistent hypereosinophilia. Such a purification procedure enabled us to collect in healthy controls, eosinophils (77.1 +/- 15.9% SD purity) with an appreciable cell recovery (21.7 +/- 14.0% SD) in the densest gradients ('normodense' cells). A high degree of purity was obtained in the same gradients, with leukocytes from patients with hypereosinophilia (84.4 +/- 11.9% SD pure eosinophils) but the cell recovery was significantly decreased (4.1 +/- 3.4% SD; p less than 0.001). A study of the various fractions found to contain eosinophils showed cells with an altered cellular density ('hypodense' cells) especially in marked hypereosinophilia. Furthermore, studies on leukocytes from patients with a very high hypereosinophilia (differential cell count greater than 70%) led to the recovery of almost pure fractions of eosinophils in the low density gradients. Functional studies were performed on each distinct cell fraction collected. They included investigations of their cytotoxic ability in a heterologous antibody-dependent cell-mediated cytotoxicity assay and their biochemical activity by using a previously described technique evaluating the membrane hexose transport. Variability in the functional potentialities was observed in relation to the cellular density: higher cytotoxic eosinophil abilities were noted in the case of the 'hypodense' cell population. According to biochemical criteria, these latter cells appear to be more activated and capable of responding to stimulation.

Antibody-Dependent Cell Cytotoxicity↗

Involvement of immunoglobulin E in the secretory processes of alveolar macrophages from asthmatic patients.

Alveolar macrophages from nonatopic donors were passively sensitized with allergen-specific IgE antibody from the serum of asthmatic patients. A selective release of 4-8% of the lysosomal beta-glucuronidase of these cells occurred within 30 min of contact with the related allergen or with anti-human IgE antibody, in the absence of any mast or basophil cells. The cell reactivity was dependent on the interaction of macrophages with IgE, as shown by the disappearance of the allergen-induced enzyme release after heating or IgE-immune adsorption of the sensitizing serum, but not after IgG-adsorption. Alveolar macrophages from asthmatic patients behaved similarly to passively sensitized normal macrophages. Contact with the related allergen or with anti-IgE antibody induced the same percentage of enzyme release, demonstrating that these cells possess allergen-specific IgE bound on their surface. 18% of them formed rosettes with anti-IgE-coated sheep erythrocytes, and 15-22% with allergen-coated erythrocytes, but lost this property after preincubation with the specific allergen. The presence of IgE-specific receptors on the macrophage surface was demonstrated both at the ultrastructural level with immunoperoxidase labeling, and at low magnification by the formation of 15-18% rosettes with human IgE-coated erythrocytes. The formation of such rosettes was inhibited after incubation of alveolar phagocytes with aggregated myeloma IgE. On the basis of these observations, the participation of the alveolar macrophages in IgE-mediated pulmonary hypersensitivity must be considered. Its precise involvement requires, however, further investigations.

Adult↗

Onchocerca volvulus: detection of circulating antigen by monoclonal antibodies in human onchocerciasis.

A monoclonal antibody of the IgM class recognizing Onchocerca volvulus circulating antigen (COA) was obtained. This monoclonal antibody was used in a radioimmunoprecipitation-PEG assay (RIPEGA) to detect circulating antigen in onchocerciasis patients' sera. COA could be detected in 63 (80%) of the 79 African patient sera tested, and in 126 (76%) of the 164 Indian (Venezuela) sera studied. There was no direct correlation between the presence of COA detected in the patient serum and the level of microfilarodermia. The RIPEGA using this monoclonal antibody detected COA in 91% of children under 10 years old, whereas the microfilarodermia in this group was positive in only 52% of the cases. The specificity of this test is improved compared to the results obtained with polyclonal antibodies. Immunofluorescence studies suggest that the COA might be located in the microfilaria cuticle.

Adolescent↗

Trypanosoma cruzi: variation in susceptibility of inbred strains of rats.

Eight strains of male rats (AUG, BN, LEW, LIS, WAG, F 344, LOU/M, DA) and 3 strains of female rats (LEW, F 344, KGH) were challenged with 15 X 10(4) trypomastigotes of the Tehuantepec strain of T. cruzi. Parasitemia and mortality were observed for 60 days. Varying degrees of susceptibility were demonstrated between strains: complete resistance (R), no parasitemia; low resistance (LR), mild parasitemia; and no resistance (NR), high parasitemia. The differences in susceptibility to T. cruzi, using inbred strains of rats, were unrelated to Rt-1 haplotype. However, the level of parasitemia and host survival are not necessarily related; both male and female F 344 hosts are susceptible (NR) to T. cruzi but only females survive.

Animals↗

Enhancement of eosinophil effector function by soluble factors released by S. mansoni: role of proteases.

Schistosomulum-released products (SRP) have been shown to enhance both expression of rat and human eosinophil Fc receptors and IgG-dependent cytotoxicity. The present work provides additional evidence of the secretion of eosinophil-enhancing factors by schistosomula and other developmental stages of schistosomes, including adult worms. The heat lability, as well as the strong inhibition of the stimulating activity of SRP by the protease inhibitor Trasylol, suggest that thermolabile proteases secreted by the parasite are involved in this mechanism. The purification of the schistosome proteases by preparative isoelectric focusing and gel filtration demonstrated that neutral proteases able to hydrolyze the collagenase substrates Azocoll and Z-Gly-Pro-Leu-Gly-Pro are able to significantly enhance eosinophil effector functions. Purified Clostridium histolyticum collagenase was also able to mimic the enhancing effect of schistosome proteases, suggesting involvement of a collagenase-like activity of the enzymes in the eosinophil stimulation.

Animals↗

[Effector functions of the polynuclear eosinophil].

The effector function of eosinophils is studied in experimental models, emphasizing the prominent role played by antibodies among which IgE, and also the activation of the cytotoxic activity by mast cell-derived ECF. A tetrapeptides. The demonstration of the cytolytic effect of basic proteins present in eosinophil granules allows to clarify this mechanism on a molecular basis. Eosinophil effector function is then envisaged in various clinical situations. In pulmonary eosinophilias, a relation appears between the detection of proteins released by eosinophils and the tissue damage. Eosinophils seem also to be implied in the inflammatory process characteristic of endomyocardial disease or in Crohn's disease. Whereas they were first considered as beneficial cells for the host, the eosinophil granulocytes may therefore express according to the targets, a dual either beneficial or nocious function.

Animals↗

Induction of non-specific human suppressor cells in vitro by defined Onchocerca volvulus antigens.

In the present study the activity of Onchocerca volvulus total antigens (OVA) on the proliferative response of human lymphocytes from healthy donors was investigated. Normal human lymphocytes were cultured for 72 h with polyclonal activators, phytohaemagglutinin (PHA) or pokeweed mitogen (PWM), together with OVA, and thymidine uptake was measured. The proliferation of normal lymphocytes was markedly inhibited by the parasite antigens. The inhibition was not attributable to a cytotoxic effect of OVA, since at least 80% viable cells were recovered at the end of cell cultures. The inhibition was not abrogated by removal of the adherent cell population. The passage of OVA through immunosorbent column containing human antibodies to O. volvulus significantly reduced the suppressive activity of OVA. The in vitro response to mitogens (PHA, PWM) of normal human lymphocytes was suppressed by co-culture with allogeneic or syngeneic lymphocytes, which had previously been exposed for 72 h to OVA. The suppression was not abrogated by the irradiation of mononuclear cells before the exposure to OVA. A significant reduction of the suppression was however observed when OVA pre-treated cells were T cell depleted by centrifugation of E rosettes. Thus, parasite antigens, which are recognized by antibodies in infected human sera may participate in the modulation of the cellular immune response during O. volvulus infection by inducing suppressor cells. This suppression could in addition contribute to the survival of the parasite in its host.

Animals↗

Aminopeptidase activity in adult Schistosoma mansoni.

An aminopeptidase activity capable of hydrolysing leucine 4-nitroanilide and alanine 4-nitroanilide at pH 7.0 was detected in saponin-CaCl2 extracts and homogenates of adult Schistosoma mansoni. The extracts were also capable of acting on synthetic dipeptides at the same pH, preferentially hydrolysing peptide bonds following leucine, alanine, or proline N-terminal residues. Imide bonds were not hydrolysed. The hydrolysis of leucine 4-nitroanilide was apparently stimulated by thiols, strongly inhibited by 1 mM 4-chloromercuric benzene sulfonic acid, and partially inhibited by 1 mM 1,10-phenanthroline.

4-Chloromercuribenzenesulfonate↗

Allergens of Schistosoma mansoni. I. Comparison of the IgE response in human and experimental infections towards characterized allergens from adult worm products.

The reaction of adult worm products of Schistosoma mansoni with IgE antibodies in infected human and Fischer rat sera has been studied using the Prausnitz-Küstner test and the radioallergosorbent test. Incubation of worms in water released most of the soluble material reacting with both rat and human sera in the radioallergosorbent test. Sera from infected Fischer rats recognized a fraction with pI 4.9-5.2 separated by preparative isoelectric focusing throughout the time course of infection, whereas human sera reacted with material focusing between pI 4.4 and 6.0. A peak of allergenic activity with an apparent molecular weight between 70,000 and 150,000 was obtained by gel filtration. Human bilharzian sera also reacted with material in the molecular weight range 12,000-25,000. Allergenic material bound specifically to concanavalin A-Sepharose, Lens culinaris agglutinin-Ultrogel, and wheat germ agglutinin-Ultrogel, but substantial allergenic activity was also present in unbound fractions.

Allergens↗

Immunologic response of athymic rats to Schistosoma mansoni infection. II. Antibody-dependent mechanisms of resistance.

The responses of congenitally athymic rats to Schistosoma mansoni were compared to thymic reconstituted, heterozygous littermate controls, and inbred Fischer rats. The mechanisms of the impaired resistance of athymic rats to initial exposure and re-exposure to S. mansoni were investigated by the study of various parameters of antibody response. The uninfected athymic animals demonstrated normal levels of total IgM but reduced levels of total IgG2a and IgE. After infection with S. mansoni, the immunoglobulin increases in athymic rats were less than those observed in heterozygote control rats. In addition, the level of anti-S. mansoni IgG antibody, utilizing ELISA assay, was reduced. Furthermore, the functional avidity of the IgG2a antibody, which was produced by the athymic animals, was significantly lower than that of control heterozygote and Fischer animals. Similarly, the levels of IgE and IgG2a anaphylactic antibodies were reduced in the congenitally athymic animals. After thymic reconstitution and exposure to S. mansoni of the congenitally athymic animals, all of these parameters became similar to the analogous value obtained from exposed heterozygous and homozygous animals. In vitro studies of antibody-dependent cell-mediated cytotoxicity (ADCC) activity indicated that the antibody response of the congenitally athymic animals was characterized by significant reductions in IgE-macrophage-mediated, IgG-eosinophil-mediated, and IgE-eosinophil-mediated cytotoxicity directed against schistosomula. These results, coupled with previously reported in vivo observations, that athymic animals produced antibody that was less capable of transferring resistance in adoptive-challenge experiments, suggest that the mechanisms of impaired resistance in the congenitally athymic rat may involve the failure to develop adequate, functional ADCC mechanisms. As such, these studies suggest a relationship between in vivo resistance and possible in vitro mechanisms of that resistance.

Animals↗

[Production of monoclonal antibody anti-antigen 5 for Trypanosoma cruzi].

Monoclonal antibodies against Trypanosoma cruzi have been produced by fusion of Sp 2/0 myeloma cells and splenic lymphocytes from BALB/c Mice immunized with a T. cruzi antigenic fraction. Antigenic studies of these monoclonal antibodies have led to the identification of IgG 1 antibody against the component 5 specific for T. cruzi (cellular clone II 190/151). These monoclonal antibodies will give rise not only to new diagnostic and epidemiological perspectives but will also aid in achieving a better understanding of the biological role of this antigen.

Animals↗

Transplacental transfer of rodent microfilariae induces antigen-specific tolerance in rats.

Microfilariae are the smallest form in the life-cycle of filarial nematode parasites. They are released by the adult female worms and migrate through the blood and extracellular fluids where they can be transmitted by vectors. A few reports have indicated the possibility of the transmission of microfilarial infection from mother to offspring. We have infected rats with adult females of the rodent filaria, Dipetalonema viteae, and report here that the transfer to D. viteae microfilaria does indeed occur through the placenta. Exposure to specific antigens early in development can readily induce immune tolerance. We observed that a state of reversible immune unresponsiveness occurred in rats as a result of pre- and post-natal exposure to microfilariae and this was associated with impairment of T-cell responses. The induction of tolerance allowed D. viteae infective larvae to reach maturity in the Fischer rat which is otherwise innately resistant to this practice.

Animals↗