Suppressive effect of O,O-dimethyl, S-ethyl phosphorothioate on immune response.
The effect of O,O-dimethyl, S-ethyl phosphorothioate (OO-Me S-Et) on macrophage function and the responses of T- and B-cells of the immune system were investigated using an in vitro model. The role of glutathione (GSH) enhancement of OO-Me S-Et suppression of immune responses was studied after either direct culturing with spleen or B-cells alone or coculture of B-cells with either B- or T-cells with or without preincubation with OO-Me S-Et and glutathione enriched cytosol. The results indicated that OO-Me S-Et, when preincubated with GSH, suppresses immune responses through an inhibition of B- and T-cell functions. Both cytotoxic T-lymphocyte (CTL) generation and antibody production were impaired. In mixing experiments of pretreated and normal cells, the inhibitory effect was also observed on macrophages and helper T-cells responding to a T-dependent antigen. It appears that the immunosuppressive effect of OO-Me S-Et is due to impairment of collaboration of T- and B-cells, i.e., mainly due to impairment of T-cell functions. The immunotoxic effect was only detectable when glutathione was present in the preincubation mixture.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000921:Antibody-Producing Cells / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects; D001711:Biotransformation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004912:Erythrocytes / Q000276:immunology; D005978:Glutathione / Q000378:metabolism; D007109:Immunity / Q000187:drug effects*; D007165:Immunosuppression Therapy; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D063086:Organothiophosphates / Q000378:metabolism / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects; D014301:Trinitrobenzenes / Q000494:pharmacology
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D014301:Trinitrobenzenes; C045368:O,O-dimethyl S-ethyl phosphorothioate; D005978:Glutathione