In vivo and in vitro evidence for extracellular caspase activity released from apoptotic cells

While caspases play an established role as intracellular executors of apopt osis, little is known about extracellular activities of this ubiquitously e xpressed family of proteases, We demonstrate here that recombinant caspase- 3 retained enzymatic activity in various extracellular fluids. Experiments with cell lines, primary cells, and mice with fulminant CD95-triggered hepa titis showed that significant amounts of DEVD-aminofluoromethylcoumarine-cl eaving activity, indicative of active effector caspases, were released into the medium/plasma during apoptosis, Furthermore, caspase activities were d etected in liquor samples from human head trauma patients. These findings w arrant closer investigation of DEVDase activity as a diagnostic marker, and of potential extracellular substrates for caspases, (C) 2001 Academic Pres s.