Natural killer cell cytotoxicity: role of calmodulin.
The phenothiazine derivatives, fluphenazine and trifluoperazine which are known to bind to calmodulin and to inhibit its activity, abrogate the development of both spontaneous and interferon-enhanced cytotoxicity of mouse splenic lymphocytes enriched for NK cell activity. Phenothiazines also inhibit the rapid increase in cyclic GMP levels in interferon-treated splenic lymphocytes. Furthermore, treatment of mouse splenic lymphocytes with electrophoretically pure interferon, alpha/beta caused a marked decrease in the level of calmodulin within 1 to 4 hours. These results provide evidence that calmodulin may play a role in the development of NK cell cytotoxicity and that the effect of interferon on calmodulin may constitute part of the molecular mechanism of interferon action.
D000818:Animals; D002147:Calmodulin / Q000097:blood / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005476:Fluphenazine / Q000494:pharmacology; D066298:In Vitro Techniques; D007372:Interferons / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008979:Moloney murine leukemia virus / Q000276:immunology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D014268:Trifluoperazine; D007372:Interferons; D006152:Cyclic GMP; D005476:Fluphenazine