[Functional activity of peritonal macrophages in liver immune damage of cellular and antibody genesis in mice].

The aim of present work was to compare the functional activity of peritoneal macrophages (Mf) at T-cellular and antibody induced hepatitis in mice of CBA line. T-cellular hepatitis was caused by concanavalin A (ConA), antibody-induced hepatitis was caused by administration of xenogenic anti-liver antibodies: gamma-globulin fractions of antihepatocytotoxic serum (gamma-AHCS). It was found that single injection of ConA or gamma-AHCS caused damage of liver with cytolytic syndrome through 20 hours. Functional activity of Mf in these conditions was significantly different. Application of ConA resulted in the decrease in phagocytosis of latex particles and oxygen-dependent metabolism; application of gamma-AHCS--to increase of these processes. Weakening of Mf activity may be one of the reasons for the decrease of dead cell eliminations that results in the maintenance of inflammatory reaction. At the same time significant amplification of phagocytic Mf activity may be one of the pathways of free radical endogenic sources increase that causes cell alteration and plays its role as mediators at inflammation.

[Functional activity of the peritoneal macrophages in mice with concanavalin A-induced hepatitis].

Hepatitis of T-cell genesis, a model of autoimmune damage of human liver, was caused in mice of CBA line by concanavalin A (Con A). The damage of liver was examined by activities of transaminases (alanine aminotransferase, aspartate aminotransferase) and alkaline phosphatase in mice blood plasma. Functional activity of macrophages in peritoneal fluid was studied by examination of phagocytosis of latex particles and oxygen--dependent metabolism (nitro-blue-tetrazolium- test). We demonstrated that a single intravenous injection of Con A in different doses (15 and 30 Mg/kg of body weight) caused acute hepatic damage in 20 hours. Weakening of macrophage functional activities may be one of the reasons of decrease in dead cells elimination following induction of immune hepatitis, it may support inflammatory reaction and promote the development of autoimmune process.

[The role of nitric oxide in the development of humoral immune response in mice].

The immune response in CBA mice was evoked by injection of sheep erythrocytes. The number of antibody-producing cells in the spleen, as well as nitric oxide production, oxygen-dependent metabolism and 5"-nucleotidase activity of peritoneal macrophages and lymphocytes were studied on days 1-5-14 after immunization. It was shown that during the inductive phase of the immune response (day 1), the peritoneal cells increased nitric oxide production, while later their functional activity increased and NO level became normal. The use of NO-synthase inhibitors (non-selective L-NNA and iNOS inhibitors SMT and dexamethasone) increased the immune response and decreased the macrophage functional activity. The use of NO-donator SNP resulted in reverse effect: decrease of the immune response and stimulation of peritoneal cells functional activity. The data obtained indicate that nitric oxide participates in the immune response regulation, in particular, through the suppressive effect of macrophages.

[Effect of inhibitors of cyclooxygenase and lypoxygenase pathway of metabolism of arachidonic acid on the development and suppression of the immune response in mice]. / Vplyv blokatoriv tsyklo- ta lipoksyhenaznoho shliakhiv metabolizmu arakhidonovoï kysloty na rozvytok i supresiiu imunnoï vidpovidi u myshei.

The influence of indomethacin (IM) and nordihydroguaiaretic acid (NDGA) as inhibitors of cyclooxygenase and lypoxygenase pathways of arachidonic acid metabolism, accordingly, on the development of the immune response (IR) to sheep red blood cells (SRBC), as well as on the formation and functional activity of the antigen-induced (by the tolerogenous dose of SRBC) T-suppressors (AITs) was studied. Investigation was carried out on mice of line CBA. The IR was estimated by quantity of antibody-forming cells in the mouse spleen. The functional activity of AITs was determined in the transfer adopting system by the intensity of IR suppression in mice--recipients. The data obtained have demonstrated, that both inhibitors mainly stimulated the IR which was more expressed at NDGA application and depended on a phase of the IR. The stimulation of the IR was related with a suppression of AITs and a decrease in their functional activity.

[Effect of inhibitors of cyclooxygenase and lipoxygenase pathways of arachidonic acid oxidation on the immune response and the activity of the monoxygenase system and lipid peroxidation in the spleen and liver in mice]. / Vplyv blokatoriv tsyklooksygenaznogo ta lipoksygenaznogo shliakhiv metabolizmu arakhidonovoï kysloty na imunnu vidpovid', aktyvnist' monooksygenaznoï systemy i perekysnogo okysnennia lipidiv u selezintsi ta pechintsi myshei.

In experiments on CBA mice we studied an immune response (IR) to sheep red blood cells, the activity of monooxygenase system and lipid peroxidation (LP) in a spleen and a liver after administration of indomethacin (IND) and nordihydroguaiaretic acid (NDGA) as the inhibitors of cyclooxygenase and lypoxygenase pathways of oxydation of arachidonic acid consequently. We have found that the both inhibitors changed differently the intensity of IR during its development. IND and NDGA activate the accumulation of antibody-forming cells in the mouse spleen in a dose-dependent fashion at both the inductive and fading phases of IR. At the productive phase these changes are less expressed and they are different depending on the dose of NDGA: the smaller dose increases the immune response and the bigger one decreases it a bit. Changes in the activity of the monooxygenase system in spleen and liver, affected with the both inhibitors, independing on the dose, were of different direction: after IND administration the activity increased, but after NDGA administration it decreased at all the terms of investigation, excluding the term of the 5-th day (productive phase of IR). In these conditions changes in the activity of IR were of opposite direction as compared to the changes in the monooxygenase system.

[Oxygen-dependent processes in the liver and immunologic reactivity of rats in chronic liver damage induced by carbon tetrachloride]. / Kislorodzavisimye protsessy v pecheni i immunologicheskaia reaktivnost organizma krys pri khronicheskom porazhenii pecheni chetyrkhkhloristymuglerodom.

The chronic hepatitis in Wistar rats was induced by seven subcutaneous injections of carbon tetrachloride (0.3 ml of 50% oil solution per 1 kg of body mass) made each third day. It was shown that cytochromes P-450 and b5 content, demethylase activity in the liver microsomal fraction as well as the oxygen tension in the liver tissue were decreased, while lipid peroxidation was intensified. The PHA-induced blood lymphocyte blastogenesis was inhibited and concentration of circulating immune complexes in the blood was higher than that in intact animals.

[Changes in the activities of antigen-nonspecific helper and suppressor cells in rabbits after carbon tetrachloride-induced liver damage]. / Izmenenie aktivnosti antigennespetsificheskikh T-khelperov i T-supressorov u krolikov v usloviiakh porazheniia pecheni chetyrekhkhloristym uglerodom.

The peripheral blood helper and suppressor T cell activity in rabbits was studied by the method of concanavalin A-induced mitogenesis. Blood lymphocytes were stimulated in vitro with different concentrations of concanavalin A (8 micrograms/ml and 60 micrograms/ml, respectively). The effect of stimulated lymphocytes on proliferative response of allogenic lymphocytes to phytohaemagglutinin was investigated. The liver injury was induced by three-fold subcutaneous injections of carbon tetrachloride (1 ml of 50% oil solution per 1 kg of body mass) each third day. Histological analysis of the liver and T cell activity examinations was performed 2, 9, 16, 30 days after carbon tetrachloride administration. It was shown that the stages of the more pronounced liver injury and the less pronounced regeneration of the liver were accompanied by the increase of helper T cell activity. The stages of the intensive liver regeneration and the less pronounced liver injury were accompanied by the increase of suppressor T cell activity.

[Antigen-specific helper and suppressor activities of T-lymphocytes of the rabbit blood during the development of immunologic response to heterologous erythrocytes]. / Antigenspetsificheskaia khelpernaia i supressornaia aktivnos't T-limfotsitov krovi krolikov v dinamike razvitiia immunnogo otveta na geteroéritrotsity.

A titre of hemolysins in blood serum, helper and suppressor activity of blood T-lymphocytes in response of ++blast transformation to Con A in different doses (8 and 60 ml) and was determined in rabbits after single and two-fold (with an interval of 30 days) immunization of the ram erythrocytes. Examinations were conducted 2, 9, 16 and 30 days after antigen introduction. Peculiarities of changes in antigen-specific helper and suppressor activity of lymphocytes and their balance in dynamics of primary and secondary immune responses are determined.