Synergistic induction of endothelial tissue factor by tumor necrosis factor and vascular endothelial growth factor: Functional analysis of the tumor necrosis factor receptors

Matthias Clauss, Matthias Grell, Carmen Fangmann, Walter Fiers, Peter Scheurich, Werner Risau

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Tissue factor expression on the surface of endothelial cells can be induced by tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF) in a synergistic manner. We have investigated the role of the two different TNF receptors for this synergy. Firstly, stimulation of the 60 kDa TNF receptor (TNFR60) by a mutant of TNF specific for TNFR60 induced responses comparable to wild-type TNF. In contrast, stimulation of TNFR80 by a TNFR80-specific TNF mutein did not result in enhancement of tissue factor expression even in the presence of a suboptimal TNFR60 triggering. Secondly, we tested neutralizing TMF receptor antibodies for inhibition of tissue factor synthesis induced by VEGF and TNF. A TNFR60-specific antibody inhibited tissue factor production over a broad range of TNF concentrations, indicating an essential role of TNFR60 in the TNF/VEGF synergy. In contrast, blocking of TNF binding to TNFR80 strongly inhibited TNF-induced tissue factor expression at low, but less pronounced at high, TNF concentrations. In conclusion, these data are in agreement with a model in which TNFR80 participates in the synergy between VEGF and low concentrations of soluble TNF by passing the ligand to the signalling TNFR60.

Original languageEnglish (US)
Pages (from-to)334-338
Number of pages5
JournalFEBS Letters
Volume390
Issue number3
DOIs
StatePublished - Jul 29 1996
Externally publishedYes

Keywords

  • Receptor
  • Synergistic induction
  • Tissue factor
  • Tumor necrosis factor
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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