Vascular permeability factor: A tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration

Matthias Clauss, M. Gerlach, H. Gerlach, J. Brett, F. Wang, P. C. Familletti, Y. C.E. Pan, J. V. Olander, D. T. Connolly, D. Stern

Research output: Contribution to journalArticle

735 Scopus citations

Abstract

Systemic infusion of low concentrations of tumor necrosis factor/cachectin (TNF) into mice that bear TNF-sensitive tumors leads to activation of coagulation, fibrin formation, and occlusive thrombosis exclusively within the tumor vascular bed. To identify mechanisms underlying the localization of this vascular procoagulant response, a tumor-derived polypeptide has been purified to homogeneity from supernatants of murine methylcholanthrene A-induced fibrosarcomas that induces endothelial tissue factor synthesis and expression (half-maximal response at -300 pM), and augments the procoagulant response to TNF in a synergistic fashion. This tumor-derived polypeptide was identified as the murine homologue ofvascular permeability factor (VPF) based on similar mobility on SDS-PAGE, an homologous NH2-terminal amino acid sequence, and recognition by a monospecific antibody to guinea pig VPF. In addition, VPF was shown to induce monocyte activation, as evidenced by expression of tissue factor. Finally, VPF was shown to induce monocyte chemotaxis across collagen membranes and endothelial cell monolayers. Taken together, these results indicate that VPF can modulate the coagulant properties of endothelium and monocytes, and can promote monocyte migration into the tumor bed. This suggests one mechanism through which tumor-derived mediators can alter properties of the vessel wall.

Original languageEnglish (US)
Pages (from-to)1535-1545
Number of pages11
JournalJournal of Experimental Medicine
Volume172
Issue number6
DOIs
StatePublished - Dec 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Clauss, M., Gerlach, M., Gerlach, H., Brett, J., Wang, F., Familletti, P. C., Pan, Y. C. E., Olander, J. V., Connolly, D. T., & Stern, D. (1990). Vascular permeability factor: A tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. Journal of Experimental Medicine, 172(6), 1535-1545. https://doi.org/10.1084/jem.172.6.1535