Preparation of soluble immune response suppressor and macrophage-derived suppressor factor.
Concanavalin A-activated murine suppressor T cells act via the mediator, soluble immune response suppressor (SIRS) which non-specifically suppresses IgM and IgG antibody responses to a variety of antigens, cytotoxic T lymphocyte responses and proliferative responses to alloantigens and mitogens in vitro. SIRS is a protein with an apparent MW of 45,000-55,000; the target of SIRS is the macrophage (M phi). M phi following treatment with SIRS release a second factor, M phi-derived suppressor factor (M phi-SF), which is directly responsible for the observed suppression of responses. Moreover. M phi-SF appears to be modified SIRS by all criteria used to date; M phi-SF can be obtained by reacting SIRS with low concentrations of H2O2 in the absence of M phi. Thus, M phi appear to serve only as a source of H2O2 and the mechanism of M phi-SF action action appears to have an oxidative basis. M phi-SF activity is lost following treatment with sulfhydryl reagents such as 2-mercaptoethanol, dithiothreitol or cysteine, reducing agents such as NaBH4 and a variety of peroxidase substrates such as pyrogallol, phenylenediamine, and ascorbic acid. Additionally, M phi-SF-mediated inhibition can be reversed by high concentrations of 2 mercaptoethanol or dithiothreitol under appropriate conditions. Since M phi-SF appears to be modified SIRS, oxidized by peroxide, and not a distinct second mediator produced by M phi in response to SIRS, we propose eliminating the term M phi-SF and using SIRSox to denote the active form of SIRS produced either by the SIRS-H2O2 reaction or SIRS-treated M phi.
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D001688:Biological Products / Q000032:analysis / Q000096:biosynthesis*; D003208:Concanavalin A / Q000494:pharmacology; D004247:DNA / Q000037:antagonists & inhibitors; D006462:Hemolytic Plaque Technique; D006825:Hybridomas / Q000276:immunology; D007166:Immunosuppressive Agents / Q000032:analysis / Q000096:biosynthesis*; D007700:Kinetics; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000032:analysis / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D013491:Suppressor Factors, Immunologic
D001688:Biological Products; D007166:Immunosuppressive Agents; D008222:Lymphokines; D013491:Suppressor Factors, Immunologic; C013256:soluble immune response suppressor; D003208:Concanavalin A; D004247:DNA