Journal of Cell Science 115, e2304-e2304 (2002)
Copyright © 2002 The Company of Biologists Limited
Apoptosis vs necrosis: ceramide decides it
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 (see
p. 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 does not generate ceramide undergoes Fas-induced
apoptosis but not necrosis. Ceramide thus seems to determine how the cells
die, which could be important given that necrosis is critical for certain
immune responses.
Related articles in JCS:
- Caspase-dependent initiation of apoptosis and necrosis by the Fas receptor in lymphoid cells: onset of necrosis is associated with delayed ceramide increase
- Claudio A. Hetz, Martin Hunn, Patricio Rojas, Vicente Torres, Lisette Leyton, and Andrew F. G. Quest
JCS 2002 115: 4671-4683.
[Abstract]
[Full Text]
