ABSTRACT
Two types of experimental liver failure in mice were investigated to study the immune mechanisms of liver disease: 1) T-cell-mediated injury induced by administration of concanavalin A (ConA) and 2) antibody-mediated injury induced by administration of anti-liver antibodies (ALA, gamma-globulin fraction of sera from rabbits immunized with liver tissue). It was established, that both types of liver injury were accompanied by the activation of immune processes in the liver, as shown by the increase of liver mononuclear cell proliferation, estimated using IPO-38 monoclonal antibodies. In contrast to ConA treatment, the immune activation under ALA-treatment was also associated with the increase in the percentage of plasma cells and small lymphocytes in liver mononuclear cells. At the same time, an increase in apoptotic and necrotic mononuclear cell death was more pronounced under ConA-treatment. This was accompanied by enhanced Fas receptor expression in these cells. Thus, it was shown that in case of T-cell mediated liver injury, the balance between cell proliferation and cell death in mononuclear liver cells was shifted toward the significant increase of apoptotic and necrotic cell death, particularly Fas-mediated apoptosis, while immune processes activation and cell proliferation were more pronounced in the case of antibodies-mediated injury.
Subject(s)
Antibodies, Monoclonal/pharmacology , Cell Proliferation , Concanavalin A/pharmacology , Leukocytes, Mononuclear/pathology , Liver/immunology , Liver/pathology , Animals , Antibodies, Monoclonal/immunology , Apoptosis/immunology , Cell Death/immunology , Cell Proliferation/drug effects , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/immunology , Chemical and Drug Induced Liver Injury/pathology , Concanavalin A/immunology , Disease Models, Animal , Hepatitis, Autoimmune/etiology , Hepatitis, Autoimmune/immunology , Hepatitis, Autoimmune/pathology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Liver/drug effects , Male , Mice , Mice, Inbred CBA , T-Lymphocytes/immunology , T-Lymphocytes/pathologyABSTRACT
Experimental immune ovarian failure in CBA mice was induced by either administration of xenogenic anti-ovarian antibodies (scheme 1) or immunization with allogenic ovarian extracts (scheme 2). It was shown that both types of treatment impaired the meiotic maturation of oocytes: the number of cells at the stages of metaphase I and metaphase II decreased compared to the cells of control mice. In both schemes of experiments, impaired oogenesis was accompanied by reduction of percentage of viable follicular cells and by increase in the part of cells possessing morphological features of apoptosis. In contrast, the number of necrotic follicular cells increased in scheme 2 only. The donor of nitric oxide molsidomin (10 mg/ kg), when injected an hour before administration of xenogenic anti-ovarian antibodies or allogenic ovary extracts, improved the meiotic maturation of oocytes and favored follicular, lymph nodes and thymus cells survival by decreasing the number of apoptotic and necrotic cells.
Subject(s)
Apoptosis/immunology , Meiosis/immunology , Molsidomine/pharmacology , Nitric Oxide Donors/pharmacology , Oogenesis/immunology , Ovary/immunology , Animals , Antibodies, Monoclonal/immunology , Apoptosis/drug effects , Cell Death/drug effects , Cell Death/immunology , Cytotoxicity, Immunologic , Female , Meiosis/drug effects , Mice , Mice, Inbred CBA , Oocytes/drug effects , Oocytes/immunology , Oogenesis/drug effects , Ovary/drug effectsABSTRACT
Thromboxanes (TX) are known to have damaging effect on a liver but their influence on the cell death, in particular on hepatocyte apoptosis and its morphological features is not investigated enough. Cell death of the rat hepatocytes was investigated in primary culture by double vital staining with fluorescent nuclear stains Hoechst 33342 and propidium iodide and by electron microscopy. It was established that exogenous Tx B2 increases the amount of hepatocytes with early stages of apoptosis - the condensed chromatin and nucleus and cell size reduction. The changes in a percentage of hepatocytes with morphological features of the late stages of apoptosis - fragmented nuclei and division on apoptotic bodies were not revealed. Tx B2 intensified the carbon tetrachloride action on hepatocyte apoptotic death and increased chromatin condensation. Tx B2 application to hepatocytes injured by chenodeoxycholic acid significantly increased the amount of cells with a final stage ofapoptosis.
Subject(s)
Apoptosis/drug effects , Hepatocytes/drug effects , Thromboxane B2/pharmacology , Animals , Carbon Tetrachloride/pharmacology , Cells, Cultured , Chenodeoxycholic Acid/pharmacology , Chromatin/metabolism , Hepatocytes/metabolism , Hepatocytes/ultrastructure , Microscopy, Electron , Rats , Rats, Wistar , Staining and LabelingABSTRACT
An impairment of the meiotic maturation of the oocytes has been shown in vitro for 2 types of immune damage of the ovaries in mice induced by xenogenic antiovarial antibodies and immunization with allogenic ovaria. Impairment of the oogenesis was followed by the follicular cell death, primarily by on the apoptic way, but under the immunization with allogenic ovary a necrotic way of their death was also activated.