Involvement of tumour necrosis factor in monocyte-mediated rapid killing of actinomycin D-pretreated WEHI 164 sarcoma cells

Immunology. 1986 Oct;59(2):323-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Cytotoxins / immunology*
  • Dactinomycin / pharmacology
  • Glycoproteins / immunology*
  • Humans
  • Mice
  • Monocytes / immunology*
  • Sarcoma, Experimental / immunology*
  • Tumor Necrosis Factor-alpha

Substances

  • Cytotoxins
  • Glycoproteins
  • Tumor Necrosis Factor-alpha
  • Dactinomycin