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Biomedical subjects

M Aguet

Publications and source records attributed to M Aguet.

100 records · Page 6Linked to original sources
PubMed1981

Electrophoretically pure mouse interferon inhibits growth, induces liver and kidney lesions, and kills suckling mice.

Suckling Swiss mice were injected daily for 8 days with either electrophoretically pure (EP) mouse interferon (s.a. 4.7 x 10(8) units/mg protein), major impurities obtained in the course of purification, or partially purified mouse interferon (s.a. 1.3 x 10(7) units/mg protein). Only EP or partially purified interferon inhibited growth, induced liver and kidney lesions, and killed mice. The authors conclude that interferon itself is responsible for these effects.

Animal Population Groups↗
PubMed1980

High-affinity binding of 125I-labelled mouse interferon to a specific cell surface receptor.

Previous research suggests that interferon binds to the cell surface, possibly by attachment to gangliosides. A two-component receptor system consisting of binding and activation sites has been proposed. This hypothesis is supported by the finding that interferon inhibits binding of cholera toxin and thyrotropin to their receptors suggesting possible common receptor sites. Moreover, an antiserum against cell surface components of interferon-sensitive cells has been shown to inhibit the action of interferon. However, to understand the interaction of interferon with the cell surface requires direct ligand-binding studies. I present here direct evidence that high-affinity binding of interferon to a specific cell surface receptor is an initial step in interferon action using biologically active purified 125I-labelled mouse interferon. Labelled interferon binds specifically to interferon-sensitive mouse leukaemia L1210 cells, whereas binding to interferon-resistant L1210 cells is nonspecific. Furthermore, specific binding to monolayer cultures of mouse L929 cells is compared with nonspecific binding to chick embryo fibroblasts insensitive to the action of mouse interferon.

Animals↗
PubMed1980

Interferon enhances the expression of Fc gamma receptors.

Murine T2D4 cells derived from a T cell hybrid line were incubated with partially purified or electrophoretically pure mouse interferon and tested for the expression of Fc gamma R as assessed by a) counting the number of cells forming rosettes with IgG-sensitized sheep erythrocytes, and b) incubating the cells with heat-aggregated rabbit IgG and then determining either the number of cells stained with fluorescein conjugated goat anti-rabbit IgG or the extent of labeling by using radioactive iodinated staphylococcus protein A. Although interferon induced a rapid increase in Fc gamma R expression on the Fc gamma R-positive T2D4 cells, it did not induce either Fc gamma R on the Fc gamma R negative BW5147 cells or Fc gamma R on either cell line. Human leukocyte interferon enhanced the expression of Fc gamma R on human Burkitt cells (Daudi) but did not affect the expression of Fc gamma R on mouse cells. We suggest that interferon may influence several effector functions of the immune system by modulating Fc receptor expression.

Animals↗
PubMed1978

Induction of specific immune unresponsiveness with purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. II. An analysis of the effects measured at the cellular and serological levels.

T lymphoblasts specific for foreign histocompatibility antigens and purified via mixed leukocyte culture (MLC) and 1 g velocity sedimentation procedures can be used as autoimmunogen to produce specific immunological unresponsiveness in adult animals. This unresponsiveness is positively correlated to the production of autoanti-idiotypic antibodies in the blast immunized animals and no evidence of coexisting alloimmunity was found. We consider this autoanti-idiotypic immunity to be the specific inducing agent of the immune tolerance. The blast immunization procedure will lead to selective reduction in T-cell reactivity against the relevant alloantigens as measured by MLC, cell-mediated lympholysis, or graft-versus-host assays. However, in individual animals, dichtomy in suppression between two T-cell assays could sometimes be observed indicating elimination of only a select group of idiotypic functionally distinct population of T cells in these blast-immunized animals. Attempts to abrogate already immune animals by the autoblast procedure were successful, in part suggesting the use of the present procedure when trying to induce in accelerated reversion of such immunity.

Animals↗
PubMed1977

Induction of specific immune unresponsiveness using purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. I. Demonstration of general validity as to species and histocompatibility barriers.

Normal immunocompetent T lymphocytes can be induced into specific proliferation if confronted with the relevant alloantigen in vitro. Such mixed leuko-cyteculture-activated T lymphoblasts carring idiotypic receptors on their surface can be purified using velocity sedimentation and serve as immunogen if administered in adjuvant to the autologous host. Autoblast immunization can be shown to lead to specific, long-lasting unresponsiveness against the relevant alloantigens, while leaving reactivity against third-party antigens intact. When tested as to general validity, it could be shown to function in all species analyzed (mouse, rat, and guinea pig) as well as across both major and minor histocompatibility barriers. No negative side effects have been noted so far. It would thus seem clear that autoblast immunization using the above described scheme may serve as a general tool in inducing long-lasting, specific unresponsiveness in any species and across any histocompatibility barrier.

Animals↗
PubMed1973

Fusion of erythrocytes by Sendai virus studied by immuno-freeze-etching.

Extensive fusion of human erythrocytes agglutinated by Sendai virus was observed after 30 s of incubation at 37 C. Electron microscopy of thin sections failed to reveal the presence of virions, viral fragments, or discrete viral antigens reactive with ferritin-labeled antibody at the sites of fusion. Immuno-freezeetching of membrane surfaces demonstrated the dispersal of viral envelope antigens from what appeared to be original sites of viral attachment. Virus-induced clustering of membrane glycoproteins was interpreted as resulting from interaction of viral antigens with membrane receptor proteins and forming the structural basis for fusion of membranes with one another.

Absorption↗
PubMedDate not supplied

Absence of detectable serum interferon in acute and chronic viral hepatitis.

Amounts of interferon were measured in sera from 59 patients with acute viral hepatitis and 49 patients with chronic hepatitis B and compared to those from patients with nonviral liver disease or influenza, and from healthy controls. In all patients with acute and chronic viral hepatitis, no serum interferon could be detected, confirming data from earlier studies of acute viral hepatitis in which no circulating interferon was found. Our results disprove the view that the amounts of serum interferon, detected at the time of the acute clinical illness, may be a determinant of outcome.

Acute Disease↗
PubMedDate not supplied

Generation of nitric oxide and clearance of interferon-gamma after BCG infection are impaired in mice that lack the interferon-gamma receptor.

Mice with a targeted deletion of either the interferon (IFN)-gamma gene or the IFN-gamma receptor gene (IFN-gamma R(0/0) mice) fail to survive infection with the Bacillus Calmette-Guerin (BCG) strain of Mycobacterium bovis. Here we show that resident peritoneal macrophages isolated 2 weeks after BCG infection from IFN-gamma R(0/0) mice produced significantly less nitric oxide (NO) than wild-type macrophages. However, the response to lipopolysaccharide (LPS) was not completely abrogated in the IFN-gamma R(0/0) macrophages. BCG infection of wild-type mice led to a marked increase in their urinary nitrite/nitrate levels, as previously described. This increase in urinary nitrite/nitrate was not detected in BCG- infected IFN-gamma R(0/0) mice, indicating that no other cytokine can replace IFN-gamma as a mediator of increased NO synthesis after BCG infection in the intact organism. A comparison of circulating levels of IFN-gamma in BCG-infected animals revealed that sera from IFN-gamma R(0/0) mice contained up to 66-fold more IFN-gamma than sera from identically treated wild-type mice. To determine if the higher levels of circulating IFN-gamma were due to increased IFN-gamma synthesis, we compared the amounts of IFN-gamma mRNA present in the spleens of BCG-infected wild-type and IFN-gamma R(0/0) mice. No increase in IFN-gamma mRNA levels was detected in the spleens from IFN-gamma R(0/0) mice. Since the generation of IFN-gamma protein in cultured spleen cells was also not increased in IFN-gamma R(0/0) mice, we conclude that clearance of IFN-gamma from the circulation is impaired in IFN-gamma R(0/0) mice, thus revealing a heretofore unrecognized important role for the IFN-gamma receptor in the regulation of IFN-gamma levels in the intact organism.

Animals↗