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Regulation of endothelial monocyte-activating polypeptide II release by apoptosis

  1. Matthias Clauss
  1. Department of Molecular Cell Biology, Max-Planck-Institut für Physiologische und Klinische Forschung, Parkstrasse 1, 61231 Bad Nauheim, Germany

  1. Edited by Lloyd J. Old, Ludwig Institute for Cancer Research, New York, NY, and approved August 1, 1998 (received for review February 10, 1998)

Abstract

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.

Footnotes

    • This paper was submitted directly (Track II) to the Proceedings Office.

    • * To whom reprint requests should be addressed. e-mail: MClauss{at}kerckhoff.mpg.de.

  • ABBREVIATIONS

    EMAP II,
    endothelial monocyte-activating polypeptide II;
    IL,
    interleukin;
    Meth A,
    methylcholanthrene A;
    TNF,
    tumor necrosis factor;
    TUNEL,
    terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling;
    Z-ASTD-FMK,
    benzyloxycarbonyl-Ala-Ser-Thr-Asp-fluoromethylketone;
    Z-DEVD-CMK,
    benzyloxycarbonyl-Asp-Glu-Val-Asp-chloromethylketone;
    Z-YVAD-CMK,
    benzyloxycarbonyl-Tyr-Val-Ala-Asp-chloromethylketone;
    PARP,
    poly(ADP ribose) polymerase;
    dpc,
    days post coitum
    • Received February 10, 1998.

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