Cells that apoptose yield vesicles without releasing their content. Death by necrosis, by contrast, involves cell swelling and lysis and can therefore generate inflammatory responses. But what determines whether a cell undergoes apoptosis or necrosis? Andrew Quest and co-workers have approached this question by examining Fas-induced death of A20 B lymphoma cells (seep. 4671). They observe that— as expected — Fas ligand triggers apoptosis, and this is accompanied by and dependent on activation of caspase-8 (the initiator caspase recruited to the Fas death receptor) and caspase-3 (a downstream effector caspase). Interestingly, apoptosis only occurs in ∼60% of cells. The rest undergo necrosis, and this requires caspase-8 but not caspase-3. The authors also observe that death of A20 cells is accompanied by ceramide generation,which, like necrosis, requires caspase-8 but not caspase-3. Furthermore, they demonstrate that ceramide treatment can promote necrosis of lymphoid cells and that a lymphoid line that...

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