Involvement of tumour necrosis factor in monocyte-mediated rapid killing of actinomycin D-pretreated WEHI 164 sarcoma cells.
Human and murine monocyte-macrophages kill actinomycin D (ActD)-treated WEHI 164 sarcoma cells in a 6-hr 51Cr-release assay (drug-dependent cellular cytotoxicity, DDCC). In this study, we have investigated the cytotoxic activity of human recombinant tumour necrosis factor (hrTNF) against untreated and ActD-treated WEHI 164 sarcoma cells. Human recombinant TNF when added to the 6-hr 51Cr-release assay killed ActD-treated targets at doses ranging from 33 to 0.33 ng/ml, whereas untreated targets were resistant to lysis. The kinetics of lysis of ActD-treated targets was similar for hrTNF and blood monocytes. The protease inhibitors phenyl-methyl-sulphonyl-fluoride (PMSF) and N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) reduced the DDCC activity of monocytes, monocyte supernatants and hrTNF. Killing of drug-sensitized target cells by monocyte supernatants was totally inhibited by a rabbit anti-TNF serum. These, as well as previous data on the physicochemical properties of the soluble cytotoxic factor released by monocytes, suggest that rapid monocyte-mediated killing of ActD-pretreated WEHI 164 sarcoma cells involves TNF or TNF-like molecules.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003603:Cytotoxins / Q000276:immunology*; D003609:Dactinomycin / Q000494:pharmacology; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D012513:Sarcoma, Experimental / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha
D003603:Cytotoxins; D006023:Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin