Endothelial monocyte-activating polypeptide-II (EMAP-II): a novel inducer of lymphocyte apoptosis

Abstract

The novel, proinflammatory cytokine endothelial monocyte-activating polypeptide-II (EMAP-II) was first found in tumor cell supernatants. EMAP-II is closely related or identical to the p43 auxiliary protein of the multisynthase complex, which is involved in protein synthesis. In vitro, EMAP-II induces procoagulant activity, increased expression of E- and P-selectins and tumor necrosis factor receptor-1, and ultimately, programmed cell death (apoptosis) in cultured endothelial cells. EMAP-II is also chemotactic for monocytes and neutrophils. However, the role of the p43/EMAP-II cytokine form in tumors is not understood. We hypothesized an immune-regulatory role within neoplastic tissues and investigated its effects on lymphocytes. EMAP-II causes a dose-dependent inhibition of proliferation and apoptosis in Jurkat T cells and mitogen-activated peripheral blood mononuclear cells. Coculture with DLD-1 colorectal cancer cells or media conditioned by these cells induces apoptosis in Jurkat cells, which is partially reversed by antibodies against EMAP-II. Our data suggest that EMAP-II constitutes a component of a novel, immunosuppressive pathway in solid tumors, which is not normally expressed outside the cell but in tumors, may be subject to abnormal processing and released from tumor cells.

Identification of CD23 as a functional receptor for the proinflammatory cytokine AIMP1/p43

“…It was later found to possess cytokine activity including angiostatic or pro-apoptotic functions (Murray et al, 2004;Haridas et al, 2008). In this study, our data shows that AIMP1-(101-192) is a binding site for CD23 and induces TNF-a secretion.…”

Proteomic analysis of mantle-cell lymphoma by protein microarray

“…p43/EMAPII is a cytokine 30 that has recently been reported to induce lymphocyte apoptosis. 31,32 Because recent studies have implicated EMAPII in tumor-induced immunosuppression, 32 it is possible that p43/EMAPII overexpression helps MCL evade the immune system and contributes to resistance of MCL to immunotherapeutic approaches. Protein phosphatase inhibitor-2 serves dual functions in signal transduction pathways.…”

Expression and function of endothelial monocyte-activating polypeptide-II in acute lung inflammation

“…Mature EMAP-II is derived from a precursor proEMAP-II/p43 molecule which is a part of the macromolecular aminoacyl-tRNA synthetase complex [3][4][5]. There is recent evidence that proEMAP-II/p43 of hamster, rat and sheep origin has a molecular weight of 43 kD while that of humans is 34 kD [4,6]. The immunohistological expression of aminoacyl-tRNA synthetase is ubiquitous in the human body, while the p43 component is cleaved and secreted under specifi c conditions [3,7,8].…”