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Biomedical subjects

M Capron

Publications and source records attributed to M Capron.

At least 145 records · Page 8Linked to original sources
PubMed1985

Defined antigens secreted by the larvae of schistosomes protect against schistosomiasis: induction of cytotoxic antibodies in the rat and the monkey.

The study of the immunology of schistosomiasis has allowed a clear understanding of the basic mechanisms of resistance, emphasizing the important role played by cellular and humoral factors. Whereas the production of polyclonal or monoclonal antibodies and the precise inventory of immune effector mechanisms in the rat and in man have led to the identification of potentially protective antigens, immunization with soluble schistosome components has not allowed a successful control of the destruction of schistosomula after infection. The experiments reported here show that schistosomulum-released products (SRP) were able to induce the production of antibodies, in the rat and the monkey, highly cytotoxic in antibody-dependent cellular cytotoxicity, using monocyte monolayers, platelets or eosinophils as effector cells. The immunization of rats with either total SRP or 25-30-kDa molecules purified from schistosomula conferred a significant protection towards a challenge infection by the parasite. IgE and to a lesser extent IgG antibodies represented the major humoral factors of cell activation leading to the schistosomulum killing when anti-SRP antisera, obtained after immunization of the monkey, were incubated with human effector cells.

Animals↗
PubMed1985

Eosinophil activation by lymphokines and T cell clone products in the rat.

T cell lines and T cell clones derived from inbred Fischer rats and specific for Schistosoma mansoni antigens were established. Cell-free supernatants from the T cell lines demonstrated a marked capacity to enhance IgE- and IgG2a-dependent eosinophil-mediated killing of S. mansoni larvae in vitro. In addition, supernatants from cloned T cells stimulated with concanavalin A or specific antigen, or unstimulated, enhanced IgE-dependent eosinophil-mediated helminthotoxicity. The enhancing activity in both cases was very heat-stable (100 degrees C, 10 min). We also found that clone-derived supernatants enhance eosinophil peroxidase release upon stimulation with homologous IgE and anti-IgE as well as inducing a more delayed spontaneous release of peroxidase. In view of the established thymus dependency for the development of immunity to schistosomiasis in the rat, the availability of these S. mansoni-specific cloned T cells has enabled the relationship between eosinophils, lymphocytes and anaphylactic antibodies to be examined more closely.

Animals↗
PubMed1985

Immunity after treatment of human schistosomiasis mansoni. II. Identification of resistant individuals, and analysis of their immune responses.

Intensities of re-infection were monitored at three-monthly intervals after treatment of Schistosoma mansoni infections in a group of 119 Kenyan schoolchildren, whose levels of water contact were also observed. 22 children showed high reinfection intensities (greater than 100 eggs per gram of faeces) by 12 months after treatment, and were considered to be susceptible. Out of 70 children who showed low reinfection intensities during the same period (less than 30 eggs per gram), 35 showed high levels both of total water contact and of contact with sites containing infected snails. In these children, the relative lack of reinfection could not be attributed to a lack of exposure, and they were classified as resistant to reinfection. Comparison of the two groups, resistant and susceptible, revealed no difference in pretreatment intensities of infection. However, there was a marked difference in age, the mean age of the resistant group being two years greater than that of the susceptible group, within a restricted starting age range. These findings indicated that resistance was an acquired and age-dependent phenomenon, not obviously related to previous egg-induced pathology. Studies of immune responses revealed no clearcut correlate of resistance, but there were interesting differences between the two groups. Whereas anti-egg antigen responses declined after treatment to a greater extent in the resistant than in the susceptible group, antibodies mediating eosinophil-dependent killing of schistosomula rose markedly in both groups, strongly suggesting that the resistant children were being exposed to cercariae. Anti-adult worm antibodies rose sharply in both groups immediately after treatment, and thereafter declined to pretreatment levels. Although some individual children showed high levels of IgE anti-schistosomulum antibodies, there were no significant differences between the two groups. Since all children showed detectable levels of antibodies mediating eosinophil-dependent killing of schistosomula, the possibility was considered that such antibodies might be a necessary, but not a limiting, factor in immunity. Instead, the functional state of the effector cells mediating antibody-dependent killing might be limiting. Eosinophil levels, measured as an indirect estimate of eosinophil functional activity, did not differ between the two groups. There were, however, marked differences between different individuals in their capacity to produce eosinophil-stimulating monocyte mediators, and although this cannot yet be related to resistance, this aspect is worth further study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Effects of hyperthermia on normal or neoplastic rat liver.

An experimental study was conducted in rats to evaluate the sensitivity of the liver to infrared hyperthermia. A 15-min hyperthermia session treating only the liver was done in rats with a normal hepatic parenchyma and in rats with hepatocarcinoma induced by chronic 3'-diethylaminoazobenzene intoxication, at various ranges of intrahepatic temperature. In normal rats, 40-42 degrees C hyperthermia was well tolerated, but the mortality rate increased when the intrahepatic temperature exceeded 42 degrees C. In rats with tumors, a 40-42 degrees C hyperthermia session was well tolerated in case of small tumors, but resulted in a high mortality rate in case of large tumors. In all cases, death occurred as a consequence of liver injury. This study using a simple method of hyperthermia defines the thermosensitivity of the neoplastic or normal rat liver and provides a basis for further investigations on the effect of hyperthermia on experimental liver tumors.

Animals↗
PubMed1985

Cytophilic IgE on human blood and tissue eosinophils.

Flow microfluorometry (FMF) was used to investigate the presence of cytophilic Ig (IgE or IgG) and the proportion of Fc receptor (Fc epsilon R or Fc gamma R)-bearing eosinophils among eosinophils from 21 hypereosinophilic patients. In 75% of the cases, it was possible to detect cytophilic IgE, significantly associated with serum IgE levels. Moreover, when lung and blood eosinophils were compared, the proportion of occupied Fc epsilon R was significantly increased on lung eosinophils, whereas very few cells had cytophilic IgG. This work provides further evidence that cytophilic IgE is not restricted to cells with high-affinity Fc epsilon R but can also be detected on the cell populations with low-affinity IgE receptors. These findings support the view that eosinophils can act as effector cells in immediate hypersensitivity reactions and in diseases associated with increased IgE production and hypereosinophilia.

Eosinophilia↗
PubMed1985

Cytophilic IgE on human blood and tissue eosinophils: detection by flow microfluorometry.

Flow microfluorometry (FMF) was used to investigate the presence of cytophilic Ig (IgE or IgG) and the proportion of Fc receptor (Fc epsilon R or Fc gamma R)-bearing eosinophils among eosinophils from 21 hypereosinophilic patients. In a large majority of the cases, it was possible to detect cytophilic IgE significantly associated with serum IgE levels. Moreover, when lung and blood eosinophils were compared, the proportion of occupied Fc epsilon R was significantly increased on lung eosinophils, whereas very few cells had cytophilic IgG. This work provides further evidence that cytophilic IgE is not restricted to cells with high affinity Fc epsilon R, but can also be detected on the cell populations with low affinity IgE receptors. These findings support the view that eosinophils can act as effector cells in immediate hypersensitivity reactions and in diseases associated with increased IgE production and hypereosinophilia.

Cell Separation↗
PubMed1985

Fc gamma receptors on rat eosinophils: isotype-dependent cell activation.

Fc receptors for rat IgG subclasses (IgG2a, IgG2c, and IgG1) were studied on rat eosinophils by rosette formation with erythrocytes coated with monoclonal immunoglobulin (Ig) or anti-Ig antisera in a reverse assay. Inhibition experiments revealed that IgG2a and IgG2c bind to the same receptor (IgG2a/IgG2c Fc receptor), distinct from the receptor for IgG1. In addition to the recent demonstration of the blocking effect of IgG2c antibodies in immunity to schistosomes, the present results show that the existence of this common receptor led to the specific inhibition by IgG2c of IgG2a-mediated eosinophil peroxidase release. Kinetic experiments on Schistosoma mansoni-infected rat eosinophils indicate that the IgG2a/IgG2c Fc receptors were occupied by cytophilic antibodies of the IgG2a isotype during the early phase of infection and by IgG2c thereafter. By rosette experiments it was possible to displace both in vivo and in vitro cytophilically bound IgG2a from its receptor. These results confirm, therefore, the major role played by antibodies in the modulation of eosinophil effector function during schistosomiasis. They underline, moreover, the possible isotypic regulation of cell activation.

Animals↗
PubMed1985

Extracellular release of rat eosinophil peroxidase (EPO) I. Role of anaphylactic immunoglobulins.

The release of intracellular peroxidase (EPO) was investigated in order to evaluate rat eosinophil activation by various immunoglobulin (Ig) isotypes. After successive incubations with purified rat IgG1, IgG2a, IgG2b, IgG2c, IgE, or IgM and their respective anti-Ig antisera, eosinophils released significant amounts of EPO (up to 26% of the intracellular content) only in the case of Ig with anaphylactic activities (IgG2a and IgE). Other classes and subclasses were unable to induce EPO exocytosis. Selective depletion and reconstitution experiments suggested that mast cells were not required in this process. Similar levels of EPO could be released after interaction of eosinophils with antigen-antibody complexes (IgG2a monoclonal antibody and Schistosoma mansoni antigen) immobilized on nonphagocytosable surfaces. These results indicate that EPO exocytosis can be obtained after cell activation with specific antibodies, and that this mechanism is independent of phagocytosis. A kinetic study of eosinophils from S. mansoni-infected rats revealed that IgG2a and IgE cytophilic antibodies induced EPO release after incubation with either specific antisera or specific antigen, which suggests the in vivo relevance of such findings. The present work underlines the parallelism of interaction of anaphylactic-type Ig with eosinophils and with mast cells. Moreover, EPO release seems to represent an interesting marker of eosinophil activation, because close relationships were established between the present findings and previous work on the effector function of rat eosinophils.

Anaphylaxis↗
PubMed1984

Rat IgE directed against schistosomula-released products is cytotoxic for Schistosoma mansoni schistosomula in vitro.

The immunogenicity of molecules shed by schistosomula into culture medium (antigens present in schistosomula-released products, SRP-A) has been studied. The results obtained show that SRP-A preferentially induce an IgE response when injected into rats, without the need for adjuvants. Moreover, anti-SRP-A IgE is cytotoxic in vitro for the larvae in the presence of macrophages, eosinophils or platelets, which have previously been demonstrated as being the three efficient killer cells for schistosomula in the presence of specific IgE. Immunofluorescence analysis locates the target antigens at the schistosomulum surface. Among the antigens recognized by anti-SRP-A IgE, two molecules of 26 and 22 kDa have been identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by western blotting.

Animals↗
PubMed1984

Interactions between eosinophils and antibodies: in vivo protective role against rat schistosomiasis.

An original protocol of cell transfer from Schistosoma mansoni-infected rats to normal recipient rats is used to investigate the protective role of phagocytic cell populations, described as effector cells in vitro, against a challenge infection with S. mansoni. Nonadherent, eosinophil-enriched and -adherent, macrophage-rich cell preparations, injected via intradermal and subcutaneous routes at the precise site of exposure to cercariae, were able to significantly protect the recipient rats. The time-course study of this protective effect according to the time after infection of donor rats revealed that eosinophils were the major cell population involved in the early phase of infection (4 to 5 weeks), whereas macrophages could also be incriminated thereafter. A rosette assay using anti-immunoglobulin-coated erythrocytes indicated a sequence of the various antibody isotypes under study (IgG1, IgG2a, IgE) on the eosinophil surface, during the course of infection. As previously shown in vitro, cytophilic antibodies seemed to participate in the protective effect of eosinophils, since eosinophil-enriched cells from normal rats, sensitized in vitro with immune complexes present in infected rat serum, could also confer significant protection. These observations establish therefore the relevance between our previous in vitro studies and rat resistance to a challenge infection with S. mansoni, underlining the major role played by the interaction between antibodies and phagocytic cells (eosinophils and macrophages).

Animals↗
PubMed1984

Role of IgE receptors in effector function of human eosinophils.

After analysis of the technical parameters of the rosette assay with human IgE-coated erythrocytes, Fc epsilon receptors for IgE (Fc epsilon R) on human peripheral blood eosinophils were compared to Fc epsilon R on lymphocytes and monocytes. Antibodies directed against Fc epsilon R on lymphocytes and monocytes inhibited the IgE rosettes formed by eosinophils from hypereosinophilic patients, which suggests that Fc epsilon R on eosinophils were antigenically related to Fc epsilon R on lymphocytes and monocytes. Fc epsilon R on human eosinophils were shown to participate in the killing effect of Schistosoma mansoni schistosomula in vitro in the presence of purified eosinophils from highly hypereosinophilic patients (blood counts greater than 3000/mm3) and anti-schistosomula IgE antibodies present in S. mansoni-infected patient sera. Similar levels of inhibition of cytotoxicity were obtained after preincubation of eosinophils with aggregated human IgE or with anti-Fc epsilon R antibodies, whereas preincubation with aggregated IgG or with anti-C3b receptor antibodies did not decrease the killing effect for schistosomula targets. This IgE-dependent cytotoxic capacity seemed restricted to eosinophils with an abnormally low density ("hypodense" cells) present only in highly hypereosinophilic patients. These observations might be related to nonparasitic situations in which increased levels of IgE and tissue or blood eosinophils are observed.

Antilymphocyte Serum↗
PubMed1984

[Participation of the IgE receptor in the toxicity of blood platelets against schistosomes].

Human blood platelets, incubated with the serum from patients with schistosomiasis or allergic asthma, became cytotoxic for schistosome larvae, in an allergen-specific mechanism linked to surface bound IgE on platelets. Cytotoxic factors, among which oxygen metabolites might be involved, were able to kill schistosomula through platelet-retaining filters. Flow cytometry showed that platelets bearing IgE receptors represented a subpopulation, the percentage of which significantly increased in patients with high levels of circulating IgE.

Asthma↗
PubMed1984

Heterogeneity of human eosinophils. II. Variability of respiratory burst activity related to cell density.

Recent work has suggested that there may be heterogeneity amongst human eosinophils. In order to study this further, blood and tissue eosinophils were separated by density gradient centrifugation in discontinuous gradients of metrizamide. Blood eosinophils were obtained from 16 patients with blood eosinophil counts above 1 X 10(9)/l. Resident eosinophils were isolated from alveolar fluid in three of these patients and from pleural effusion in two others. A large proportion of the eosinophils in these patients were of light buoyant density (hypodense) and a high percentage of these showed morphological evidence of hypogranulation. Hypodense eosinophils had a reduced capacity to reduce nitroblue tetrazolium or develop chemiluminescence after stimulation with phorbol myristate acetate. It was concluded that there is structural and metabolic heterogeneity amongst blood and tissue eosinophils in patients with a variety of eosinophilic disorders.

Centrifugation, Density Gradient↗
PubMed1984

Blocking activity of rat monoclonal antibodies in experimental schistosomiasis.

Rat IgG2c monoclonal antibodies have been produced after fusion of spleen cells from LOU/C rats infected with Schistosoma mansoni for 5 wk and IRF983F nonsecreting rat myeloma. The cell supernatant of an IgG2c-producing clone (IPLSm3), as well as ascitic fluids induced by this clone, revealed anti-S. mansoni activity detected by immunofluorescence on schistosomula sections. Antigenic analysis performed with IPLSm3 IgG2c antibody allowed to isolate onto the S. mansoni schistosomula surface a 38,000 dalton antigen previously characterized with the protective IPLSm1 IgG2a monoclonal antibody. Although IPLSm3 IgG2c did not exhibit any killing activity in vitro against schistosomula in the presence of complement, macrophages, or eosinophils, it was shown to strongly inhibit the eosinophil-dependent cytotoxicity mediated by IPLSm1 IgG2a antibodies. The blocking activity of IgG2c antibody was further demonstrated in vitro by the use of F(ab')2 fragments and in vivo by the inhibition of passively transferred immunity conferred by the IgG2a protective monoclonal antibody. These results indicate that blocking antibodies could play an important role in the expression of protective immunity during schistosome infection.

Animals↗
PubMed1983

Evaluation of isolated human hepatocytes.

This preliminary study reports the functional capacities of freshly isolated human hepatocytes in regard to their energetic metabolism and monooxygenase activities. Incubated for 30 or 60 min, isolated cells maintain their membrane integrity, ATP and reduced glutathione content and redox potential estimated by means of lactate to pyruvate and beta-hydroxypyruvate to acetoacetate ratios. Three monooxygenase activities, supported by different isoenzymes of cytochrome P-450 are determined by the accumulation of unconjugated metabolites: their relative magnitudes are similar to those observed in microsomes, indicating a good preservation of hydroxylase activities during cell isolation and incubation. Although incubations did not exceed 60 min, one can conclude that human hepatocytes maintain their viability and metabolic capacities after isolation and might be considered in transplantation process for the treatment of acute hepatic failure. Isolated human hepatocytes might be also used as a tool for studying biochemical and toxicological effects of a drug.

Adolescent↗
PubMed1983

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↗
PubMed1983

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↗