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 prepa red from anti-Fas-stimulated JURKAT T cells, induces chromatin fragmen tation in isolated nuclei with concomitant morphological changes typic ally seen in apoptosis, The formation of this apoptotic nuclei promoti ng activity (ANPA) in JURKAT T cells after Fas antigen ligation was bl ocked by the serine protease inhibitors, TPCK and DCI, and by the inte rleukin I-P-converting enzyme inhibitor, VAD-FMK. Tn addition, chromat in degradation and morphological changes mediated by the ANPA in isola ted nuclei were inhibited by TPCK, but not by DCI or VAD-FMK, These re sults suggest that Fas-mediated apoptosis in T cells involves the acti vation of a cascade of proteases.