Modulation of anti-tumor cytotoxicity of cultured mast cells by metabolic inhibitors.
IL-3-dependent, murine mast cell lines derived from embryonic yolk sac precursors display a tumoricidal activity that is blocked by antibodies against tumor necrosis factor-alpha, indicating that this cytokine is the major mediator involved in the cytotoxic activity of the cultured mast cell lines. Further, cholera toxin strongly inhibits the cytotoxic activity of mast cells as well as their IL-3-induced DNA synthesis response but not IgE-mediated serotonin release. Cyclosporin A diminished cytotoxicity and serotonin release, but not DNA synthesis. Actinomycin D markedly suppressed the cytotoxicity of one mast cell line but only slightly suppressed that of another, whereas the IL-3-induced proliferation of both mast cell lines was strongly inhibited. Thus, our studies indicate that the cytotoxic function of mast cells is relatively independent of their degranulation and proliferation and may utilize different signalling pathways.
Manning
J K
JK
Department of Medical Microbiology and Immunology, University of Wisconsin, Madison.
Malkovsky
M
M
Meager
A
A
D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003609:Dactinomycin / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D014407:Tumor Cells, Cultured / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D016572:Cyclosporine; D002772:Cholera Toxin