Tumour necrosis factor-induced necrosis versus anti-Fas-induced apoptosis in L929 cells

Abstract

Murine fibrosarcoma L929 cells were transfected with human Fas cDNA. The mode of cell death was analysed following treatment either with tumour necrosis factor (TNF) or with agonistic antibodies to Fas. While triggering of the TNF receptors led to necrosis, clustering of the Fas antigen resulted in apoptotic cell death. N-tosyl-l-phenylalanine chloromethyl ketone and Nalpha-p-tosyl-l-lysine chloromethyl ketone, two serine protease inhibitors, has a protective effect on TNF-induced killing, while Fas-mediated cell death was rather enhanced. Lithium chloride, which had a synergistic effect on TNF cytotoxicity, did not affect Fas-mediated death, whereas staurosporine had an enhancing effect on both types of cell death. Aphidicolin and hydroxyurea, inhibitors of DNA synthesis, were able to sensitize cells to Fas-induced killing, but had no effect on TNF cytotoxicity. Finally, we demonstrate that the effect of increasing concentrations of actinomycin D or cycloheximide is very different for the two types of cell killing. We conclude that either necrosis or apoptosis can occur in the same cell type, depending on the trigger, and that, although both pathways perhaps may share some cellular components, signal transduction is different for the two types of cell death.