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


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
Issue number3
StatePublished - Jul 29 1996



  • 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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