Knies U E, Behrensdorf H A, Mitchell C A, Deutsch U, Risau W, Drexler H C, Clauss M
Department of Molecular Cell Biology, Max-Planck-Institut für Physiologische und Klinische Forschung, Parkstrasse 1, 61231 Bad Nauheim, Germany.
Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12322-7. doi: 10.1073/pnas.95.21.12322.
Endothelial monocyte-activating polypeptide II (EMAP II) is a proinflammatory cytokine and a chemoattractant for monocytes. We show here that, in the mouse embryo, EMAP II mRNA was most abundant at sites of tissue remodeling where many apoptotic cells could be detected by terminal deoxynucleotidyltransferase-mediated dUTP end labeling. Removal of dead cells is known to require macrophages, and these were found to colocalize with areas of EMAP II mRNA expression and programmed cell death. In cultured cells, post-translational processing of pro-EMAP II protein to the mature released EMAP II form (23 kDa) occurred coincidentally with apoptosis. Cleavage of pro-EMAP II could be abrogated in cultured cells by using a peptide-based inhibitor, which competes with the ASTD cleavage site of pro-EMAP II. Our results suggest that the coordinate program of cell death includes activation of a caspase-like activity that initiates the processing of a cytokine responsible for macrophage attraction to the sites of apoptosis.
内皮单核细胞激活多肽II（EMAP II）是一种促炎细胞因子，也是单核细胞的趋化因子。我们在此表明，在小鼠胚胎中，EMAP II mRNA在组织重塑部位最为丰富，在这些部位可通过末端脱氧核苷酸转移酶介导的dUTP末端标记检测到许多凋亡细胞。已知清除死细胞需要巨噬细胞，并且发现这些巨噬细胞与EMAP II mRNA表达区域和程序性细胞死亡区域共定位。在培养细胞中，前EMAP II蛋白向成熟的释放型EMAP II形式（23 kDa）的翻译后加工与细胞凋亡同时发生。通过使用一种基于肽的抑制剂可以在培养细胞中消除前EMAP II的切割，该抑制剂与前EMAP II的ASTD切割位点竞争。我们的结果表明，细胞死亡的协调程序包括激活一种半胱天冬酶样活性，该活性启动一种负责将巨噬细胞吸引到凋亡部位的细胞因子的加工过程。
