A role for histamine type II (H-2) receptor binding in production of the lymphokine, soluble immune response suppressor (SIRS).
Soluble immune response suppressor (SIRS) is an immunosuppressive protein produced by human and murine suppressor cells activated by a variety of agents. Because histamine has been reported to activate suppressor cells, the possibility that it also induced SIRS production was investigated. Human lymphocytes treated with 10(-4) M histamine for less than 1 hr released a suppressive substance into culture supernatants that was physically, functionally and antigenically similar to human SIRS. Cimetidine and ranitidine, structurally distinct histamine type II (H-2) receptor antagonists, prevented histamine-induced SIRS production. In further experiments, suppression of human polyclonal IgM PFC responses by Con A and interferons, substances that activate the SIRS pathway, was inhibited by H-2 receptor antagonists. Activation of lymphocytes to produce SIRS by Con A or interferons was blocked by cimetidine or ranitidine. These data demonstrate that production of SIRS is induced by histamine, and raise the possibility that H-2 receptor binding may play a role in the SIRS pathway.
D000917:Antibody Formation; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D002927:Cimetidine / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D006632:Histamine / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D007372:Interferons / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis*; D009404:Nephrotic Syndrome / Q000276:immunology; D011899:Ranitidine / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000502:physiology*; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D008222:Lymphokines; D011970:Receptors, Histamine H2; D013491:Suppressor Factors, Immunologic; D003208:Concanavalin A; D002927:Cimetidine; D006632:Histamine; D011899:Ranitidine; D007372:Interferons