Regulation of EMAP II by hypoxia

Susanne Matschurat, Ulrike E. Knies, Veronika Person, Ludger Fink, Benjamin Stoelcker, Chinedu Ebenebe, Heike A. Behrensdorf, Jutta Schaper, Matthias Clauss

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45 Scopus citations


Endothelial-monocyte-activating polypeptide II (EMAP II) is a proinflammatory cytokine and a chemoattractant for monocytes and granulocytes. We have previously shown that EMAP II mRNA is strongly expressed at sites of apoptosis in the mouse embryo and that the mature protein is cleaved from its cellular precursor (proEMAP II/p43) by caspase activation to become released from cells. Here we demonstrate in vivo that EMAP II mRNA expression is strongly increased in tumor necrosis factor α (TNF)-treated murine meth A fibrosarcomas and in B16 melanomas, especially in close proximity to areas of tissue necrosis. Furthermore, by means of confocal microscopy, high level expression of proEMAP II/p43 protein correlated predominantly with hypoxic but also with apoptotic cells. In vitro, EMAP II mRNA levels were not increased by hypoxia. However, high amounts of mature EMAP II protein were detected in the supernatants of hypoxic tumor cells. Unlike in apoptotic cells, neither a broad-range caspase inhibitor nor an inhibitor specific for the internal cleavage site was able to inhibit processing of proEMAP II/p43 to the mature EMAP II protein. In conclusion, these data suggest that hypoxia and apoptosis provide two alternative mechanisms of EMAP II generation by tumor cells.

Original languageEnglish (US)
Pages (from-to)93-103
Number of pages11
JournalAmerican Journal of Pathology
Issue number1
StatePublished - Jan 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Matschurat, S., Knies, U. E., Person, V., Fink, L., Stoelcker, B., Ebenebe, C., Behrensdorf, H. A., Schaper, J., & Clauss, M. (2003). Regulation of EMAP II by hypoxia. American Journal of Pathology, 162(1), 93-103.