Killing of T lymphocytes by synthetic ceramide is by a nonapoptotic mechanism and is abrogated following mitogenic activation

Ceramide induces apoptosis in leukemia cell lines and has been proposed as a potential therapeutic agent in malignancies refractory to conventional tr eatment. Here we show that synthetic N-acetyl-Derythro-sphingosine (C-2 cer amide) kills normal human T lymphocytes by a caspase-independent nonapoptot ic mechanism. By contrast, T cells were induced to caspase-dependent apopto sis by okadaic acid. Furthermore, C-2 ceramide treatment of the Jurkat leuk emia cell line induced killing by apoptosis. Activation of T lymphocytes by phytohemagglutinin abrogated killing by C-2 ceramide. The data here sugges t that ceramide triggers caspase-dependent apoptosis in leukemia cells line s, but activates caspase-independent nonapoptotic killing of resting T lymp hocytes which is abrogated following mitogenic activation. (C) 1999 Academi c Press.