INVOLVEMENT OF MULTIPLE PROTEASES DURING FAS-MEDIATED APOPTOSIS IN T-LYMPHOCYTES

The mechanism of Fas antigen-mediated apoptosis is at present unclear, We show here that the 100,000 x g supernatant from cell lysates prepared from anti-Fas-stimulated JURKAT T cells, induces chromatin fragmentation in isolated nuclei with concomitant morphological changes typically seen in apoptosis, The formation of this apoptotic nuclei promoting activity (ANPA) in JURKAT T cells after Fas antigen ligation was blocked by the serine protease inhibitors, TPCK and DCI, and by the interleukin I-P-converting enzyme inhibitor, VAD-FMK. Tn addition, chromatin degradation and morphological changes mediated by the ANPA in isolated nuclei were inhibited by TPCK, but not by DCI or VAD-FMK, These results suggest that Fas-mediated apoptosis in T cells involves the activation of a cascade of proteases.