concanavalin-a and Immune-System-Diseases

To evaluate the role of adiponectin in regulating tumor necrosis factor alpha (TNF alpha) production and preventing fulminant autoimmunological damage of hepatocytes following concanavalin A (Con A) injection into mice.. Three days after recombinant plasmids pAA-neo-mAd were injected into the mice via the tail veins, Con A was injected into the mice. Mice transfected with empty pAA-neo vector served as controls. The serum levels of alanine aminotransferase (ALT), TNF alpha and adiponectin were detected, and histological examination of livers was carried out at different time points after the Con A injection. All results were subjected to statistical analyses.. Histological examinations showed that the damage in livers of mice with high serum adiponectin levels was milder than that of the controls. The serum levels of ALT and TNF alpha were both lower than those of the controls (P less than 0.01, respectively). Statistical analyses showed the serum levels of ALT was negatively related to the levels of adiponectin in the sera (r=-0.5034).. Adiponectin is effective in protecting hepatocytes from Con A-induced immunological injury. The mechanism of this protective effect may be caused by inhibiting the synthesis and/or release of TNF alpha.

Topics: Adiponectin; Alanine Transaminase; Animals; Concanavalin A; Female; Immune System Diseases; Liver; Liver Diseases; Mice; Mice, Inbred BALB C; Tumor Necrosis Factor-alpha

Topics: Aflatoxin B1; Animals; Cell Division; Cells, Cultured; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Immune System Diseases; Leukocytes; Lipopolysaccharides; Oncorhynchus mykiss; Pokeweed Mitogens; Time Factors

The immune system of the spontaneously hypertensive rat is dysfunctional compared with that of normotensive control strains. Previous studies from our laboratory have shown that immunodepression in the spontaneously hypertensive rat was mediated by macrophages. The current study examines the mechanism for the depressed proliferative responses to concanavalin A typically observed by splenic mononuclear cells of spontaneously hypertensive rats. We tested various inhibitors of known macrophage products responsible for suppressing lymphoid function. The nitric oxide synthetase inhibitor NG-monomethyl L-arginine produced dose-dependent derepression of the proliferative responses of splenic mononuclear cells to concanavalin A. In contrast, indomethacin and catalase exhibited only weak derepression of the proliferative responses. Subsequent analysis showed that splenic mononuclear cells from spontaneously hypertensive rats generated greater nitric oxide levels than cells from Wistar-Kyoto rats, and nitric oxide levels were reduced when the inhibitor was added to splenic mononuclear cell cultures from spontaneously hypertensive rats. We further demonstrated that L-arginine is required for the development of the depressed mitogen-induced proliferative responses in these cells. Addition of L-arginine in excess of 10 microM to cultures diminished cell proliferation and increased nitric oxide. Polyclonal antibodies to murine interferon gamma reduced nitric oxide accumulation by approximately 50%, suggesting that interferon gamma is partially responsible for enhancing nitric oxide production in mitogen-stimulated splenic mononuclear cell cultures from spontaneously hypertensive rats. Thus, this study provides evidence that the immune depression observed in the spontaneously hypertensive rat is nitric oxide dependent.

Topics: Amino Acid Oxidoreductases; Animals; Arginine; Cell Division; Concanavalin A; Hypertension; Immune System Diseases; Interferon-gamma; Leukocytes, Mononuclear; Male; Nitric Oxide; Nitric Oxide Synthase; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Spleen

Immune dysfunction has been reported in spontaneously hypertensive rats (SHR), particularly in mature animals with established hypertension. The current study examined the time course of development of immune dysfunction and defined its cellular basis in male SHR and control normotensive Wistar-Kyoto rats (WKY). Mitogen-induced proliferative responses in lymphoid cells obtained from induced proliferative responses in lymphoid cells obtained from SHR thymus and spleen before (age 4 wk) and during the development of (ages 8 and 12 wk) hypertension and in age-matched normotensive WKY were monitored. A 50% reduction in concanavalin A (Con A)-induced proliferative responses was seen in SHR thymocytes compared with those of WKY at 12 wk only, suggesting differences in immature T-cell populations. Con A-induced T-cell proliferative responses in splenocytes also differed between strains: greatest (as much as 8-fold) decreases were found in 12-wk-old SHR. Similar findings were obtained in splenocytes stimulated with lipopolysaccharide (LPS), indicating differences in B-cell function. Mononuclear cells depleted of their adherent cell population were prepared from SHR and WKY at 12+ wk of age and assayed for their proliferative responses to LPS and Con A. The remaining nonadherent mononuclear cells of SHR had proliferative responses equal to or greater than those of WKY. Further, when SHR splenic mononuclear cells were allowed to adhere to plastic, and the adherent fraction was co-cultured with either SHR G-10 nonadherent or unfractionated SHR splenic mononuclear cells, proliferative responses were suppressed by as much as 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; B-Lymphocytes; Cell Adhesion; Concanavalin A; Hypertension; Immune System Diseases; Lipopolysaccharides; Lymphatic System; Lymphocyte Activation; Lymphoid Tissue; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Spleen; T-Lymphocytes

Concanavalin-A-stimulated human T lymphocytes from healthy donors and from patients suffering from diverse immune disorders were fractionated into rosette-forming (R) and nonrosette-forming (NR) cells. The separation method is based upon the ability of the lymphocytes to bind autologous erythrocytes and form autorosettes. Long-term cultures of the R and NR subpopulations were established. The activity of the culture supernatants on the T cell proliferation of normal human phytohemagglutinin (PHA)-induced lymphocytes and of a murine, interleukin-2 (IL-2)-dependent cytotoxic T cell line (CTLL) was investigated. Only the R cell line-derived supernatants from almost all patients tested evinced potent suppressor activity, those from healthy donors less so. The suppressive function was demonstrated not to be due to a cytotoxic effect since preincubation of the PHA-induced lymphocytes and CTLL cells with the factor did not diminish their proliferative capacity. Our study indicates the existence of a competitive relationship between the suppressor factor and IL-2. We found that inhibition of the proliferation decreased with the addition of increasing quantities of exogenous IL-2. We also observed that preincubating the CTLL cells with IL-2 prior to exposing them to the suppressive factor precludes inhibition of their proliferation. Phenotypic analysis of the suppressor cell line revealed that they were comprised of a T cell population which included OKT4+ and OKT8+ cells and that 99% of the cells formed autorosettes. Preliminary purification of the suppressive factor was performed by ultrafiltration and maximal suppression was exhibited by the fraction of less than 10,000 daltons. The development of suppressor cell lines from the unique population of autologous rosette-forming cells may be very helpful in studying the immunoregulatory properties of these cells and their suppressor activity.

Topics: Animals; Antigens, Surface; Bone Marrow; Bone Marrow Cells; Cell Division; Cell Line; Cell Separation; Concanavalin A; Cytotoxicity Tests, Immunologic; Humans; Immune System Diseases; Immune Tolerance; Interleukin-2; Leukocytes, Mononuclear; Mice; Mice, Inbred BALB C; Rats; Rats, Inbred Lew; Rosette Formation; Suppressor Factors, Immunologic; T-Lymphocytes, Regulatory

Con A-induced suppressor cells were studied in 20 patients with autoimmune thrombocytopenic purpura and 20 normal controls. Percentage of suppression was determined on autologous and allogenic lymphocytes during blast transformation with phytohemagglutinin (PHA). In 10 patients and 10 controls helper (T4) and suppressor (T8) subsets were also determined, using monoclonal antibodies. We found a significant decrease in patients' suppressor cell activity both with autologous and allogeneic lymphocytes. Patients' responder lymphocytes were also impaired when tested with normal suppressor cells. The numbers of T4 and T8 in patients was found to be normal although the ratio T4/T8 was somewhat lower than in normal controls. There was a significant direct correlation between the numbers of T4 of patients and their suppressor cell activity on allogeneic lymphocytes suggesting an immunoregulatory defect at the level of induction of suppressor cells.

Topics: Adolescent; Adult; Aged; Autoimmune Diseases; Child; Child, Preschool; Concanavalin A; Humans; Immune System Diseases; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Middle Aged; Phytohemagglutinins; Purpura, Thrombocytopenic; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Topics: Adult; Antibody Formation; Concanavalin A; Deoxyuridine; False Positive Reactions; Follow-Up Studies; Heroin Dependence; Humans; Immune System Diseases; Immunity, Cellular; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Iodine Radioisotopes; Lectins; Leukocytes; Liver Diseases; Lymphocytes; Methadone; Mitogens; Skin Tests; Syphilis Serodiagnosis