REGULATION OF ENDOTHELIAL MONOCYTE-ACTIVATING POLYPEPTIDE-II RELEASE BY APOPTOSIS

Endothelial monocyte-activating polypeptide II (EMAP II) is a proinfla mmatory cytokine and a chemoattractant for monocytes, We show here tha t, in the mouse embryo, EMAP II mRNA was most abundant at sites of tis sue remodeling where many apoptotic cells could be detected by termina l deoxynucleotidyltransferase-mediated dUTP end labeling. Removal of d ead cells is known to require macrophages, and these were found to col ocalize with areas of EMAP LI mRNA expression and programmed cell deat h. In cultured cells, post-translational processing of pro-EMAP II pro tein to the mature released EMAP II form (23 kDa) occurred coincidenta lly with apoptosis, Cleavage of pro-EMAP II could be abrogated in cult ured cells by using a peptide-based inhibitor, which competes with the ASTD cleavage site of pro-EMAP II. Our results suggest that the coord inate program of cell death includes activation of a caspase-like acti vity that initiates the processing of a cytokine responsible for macro phage attraction to the sites of apoptosis.