Cooperation between VEGF and TNF-α is necessary for exposure of active tissue factor on the surface of human endothelial cells

Marina Camera, Peter L A Giesen, Jay Fallon, Barbara M. Aufiero, Mark Taubman, Elena Tremoli, Yale Nemerson

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Abstract

This study was undertaken to characterize tissue factor (TF) induction, localization, and functional activity in cultured human umbilical vein endothelial cells (HUVECs) exposed to recombinant vaSCular endothelial growth factor (rVEGF) and recombinant tumor necrosis factor-α (rTNF-α). rVEGF (1 nmol/L) and rTNF-α (500 U/mL) synergistically increased TF mRNA, protein, and total activity, as measured in cell lysates. To examine surface TF expression, living cells were treated with antibody to TF and examined microscopically. Almost no staining was seen in control cells or cells treated with a single agent. In contrast, cells treated with both agonists showed intense membrane staining with surface patches, appearing as buds by confocal microscopy. To determine surface TF activity, studies were performed using a parallel-plate flow chamber, which allows detection of factor Xa generation on living cells. rVEGF and rTNF-α induced little surface TF activity (0.032±0.008 and 0.014±0.008 fmol/cm2, respectively). In combination, they significantly increased TF expression on the cell surface (0.429±0.094 fmol/cm2, P

Original languageEnglish
Pages (from-to)531-537
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume19
Issue number3
Publication statusPublished - Mar 1999

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Keywords

  • Cytokines
  • Endothelium
  • Factor Xa generation
  • Growth factors
  • Procoagulant activity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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