Increased ecto-metallopeptidase activity in cells undergoing apoptosis

Release from the cell surface of a variety of growth factors, cytokines,and proteases follows exposure to genetically stressful agents capable of indu cing apoptosis and necrosis. Increased ectoprotease activity is responsible for their release. We show that increased activity of several metalloprote ases on the HeLa cell surface occurs after stresses due to UVC, actinomycin D, cycloheximide, and cisplatinum, which induce the release of transformin g growth factor-cr (TGF alpha) and other bioactive molecules. The ectoprote ase activities increase preferentially on apoptotic cells, while little cha nge occurs in viable cells. Gross decreases, except for the putative TGF al pha ase activity, accompany necrosis. These changes may contribute to tissu e repair and the absence of an inflammatory reaction to apoptotic cell deat h. They appear to be due to preferential enzyme activation or to retention by cells undergoing significant categorical decreases in protein content. ( C) 2000 Wiley-Liss, Inc.