Soluble immune response suppressor (SIRS) inhibits microtubule function in vivo and microtubule assembly in vitro.
Soluble immune response suppressor (SIRS) is a product of concanavalin A-stimulated murine T cells that, when activated or oxidized by macrophages or H2O2 (SIRSox), suppresses in vitro immune responses and inhibits cell division by normal and neoplastic cells. SIRSox is inactivated by a variety of electron donors, which suggests that SIRSox may be an oxidizing agent. Incubation of lymphocytes with SIRSox, but not with SIRS, partially reversed concanavalin A-mediated inhibition of capping of membrane immunoglobulin on B cells, and disrupted the cytoplasmic array of microtubules visualized by fluorescence microscopy. SIRSox also inhibited microtubule assembly in vitro in a concentration-dependent manner. Inactivation of SIRSox by dithiothreitol prevented SIRSox-mediated reversal of inhibition of capping and inhibition of microtubule assembly. These results reveal a pattern of SIRSox activity similar to sulfhydryl-dependent cytoskeletal disrupting agents (e.g., N-ethylmaleimide, cytochalasin A, p-benzoquinone), and suggest that SIRSox-mediated suppression of proliferation may involve interference with sulfhydryl-dependent cytoskeletal events critical for cell division.
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D005347:Fibroblasts / Q000473:pathology; D005455:Fluorescent Antibody Technique; D007152:Immunologic Capping; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008870:Microtubules / Q000473:pathology / Q000502:physiology*; D013491:Suppressor Factors, Immunologic; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism
D008222:Lymphokines; D013491:Suppressor Factors, Immunologic; D014404:Tubulin; C013256:soluble immune response suppressor; D003208:Concanavalin A