A caspaselike activity is triggered by LPS and is required for survival of human dendritic cells

Bacterial endotoxin (lipopolysaccharide [LPS]) is a potent inducer of human dendritic cell (DC) maturation and survival. Here we show that immature DCs exposed to LPS trigger an early and sustained caspaselike activity, which can be blocked by zVAD (z-Val-Ala-Asp), in the absence of detectable caspase 8 and caspase 10 activation, or poly(ADP-ribose) polymerase (PARP)-cleaving activity. Preventing LPS-induced caspaselike activation in DC results in massive cell death. Importantly, triggering of the caspaselike activity is required for LPS-induced activation of extracellular signal-regulated kinases (ERKs) and for LPS-induced upregulation of cFLIP (Fas-associating protein with death domain-like interleukin-10-converting enzyme [FLICE]-like inhibitory protein). Therefore, a caspase-dependent pathway initiated by LPS controls survival of human DCs. (Blood. 2003; 102:2910-2915) (C) 2003 by The American Society of Hematology.