PHOSPHATIDYLSERINE EXTERNALIZATION IS A DOWNSTREAM EVENT OF INTERLEUKIN-1-BETA-CONVERTING ENZYME FAMILY PROTEASE ACTIVATION DURING APOPTOSIS

Phosphatidylserine (PS), a class of acidic phospholipids, normally loc alizes on the internal surface of cellular plasma membranes, The inter nal PS is externalized when cells undergo apoptosis; however, the mech anism for this is largely unknown. To study the mechanism of PS extern alization during development of apoptosis, we examined the correlation between the activation of interleukin-1 beta-converting enzyme (ICE) family protease and PS externalization in human monocytic leukemia U93 7 cells and in their apoptosis-resistant variants, UK711 and UK110, af ter treatment with etoposide and anti-fas antibody, We found that PS e xternalization accompanied the development of apoptosis and the activa tion of ICE family proteases in these cell lines, Furthermore, inhibit ors of ICE family proteases, Z-Asp and Z-VAD, prevented apoptosis and PS externalization in etoposide-treated U937 cells, These results indi cate that PS externalization is a downstream event of ICE family prote ase activation during apoptosis development, Because ICE family protea ses play a crucial role in apoptosis, PS externalization could be a ra tional and useful marker for the development of apoptosis. (C) 1997 by The American Society of Hematology.