title: Killing of T lymphocytes by synthetic ceramide is by a nonapoptotic mechanism and is abrogated following mitogenic activation.
abstract: Ceramide induces apoptosis in leukemia cell lines and has been proposed as a potential therapeutic agent in malignancies refractory to conventional treatment. Here we show that synthetic N-acetyl-d-erythro-sphingosine (C2 ceramide) kills normal human T lymphocytes by a caspase-independent nonapoptotic mechanism. By contrast, T cells were induced to caspase-dependent apoptosis by okadaic acid. Furthermore, C2 ceramide treatment of the Jurkat leukemia cell line induced killing by apoptosis. Activation of T lymphocytes by phytohemagglutinin abrogated killing by C2 ceramide. The data here suggest that ceramide triggers caspase-dependent apoptosis in leukemia cells lines, but activates caspase-independent nonapoptotic killing of resting T lymphocytes which is abrogated following mitogenic activation.
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D019319:Okadaic Acid / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*