Modulation of endothelial cell hemostatic properties by tumor necrosis factor.
Open Access
- 1 March 1986
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 163 (3), 740-745
- https://doi.org/10.1084/jem.163.3.740
Abstract
Tumor necrosis factor/cachectin (TNF) is a mediator of the septic state, which involves diffuse abnormalities of coagulation throughout the vasculature. Since previous studies have shown that endothelial cells can play an active role in coagulation, we wished to determine whether TNF could modulate endothelial cell hemostatic properties. Incubation of purified recombinant TNF with cultured endothelial cells resulted in a time- and dose-dependent acquisition of tissue factor procoagulant activity. Concomitant with enhanced procoagulant activity, TNF also suppressed endothelial cell cofactor activity for the anticoagulant protein C pathway; both thrombin-mediated protein C activation and formation of functional activated protein C-protein S complex on the cell surface were considerably attenuated. Comparable concentrations of TNF (half-maximal affect at approximately 50 pM) and incubation times (half-maximal affect by 4 h after addition to cultures) were required for each of these changes in endothelial cell coagulant properties. This unidirectional shift in cell surface hemostatic properties favoring promotion of clot formation indicates that, in addition to leukocyte procoagulants, endothelium can potentially be instrumental in the pathogenesis of the thrombotic state associated with inflammatory and malignant disorders.Keywords
This publication has 11 references indexed in Scilit:
- Cellular requirements for tissue factor generation by bovine aortic endothelial cells in cultureThrombosis Research, 1985
- Self-regulation of procoagulant events on the endothelial cell surface.The Journal of Experimental Medicine, 1985
- Passive Immunization Against Cachectin/Tumor Necrosis Factor Protects Mice from Lethal Effect of EndotoxinScience, 1985
- Identity of tumour necrosis factor and the macrophage-secreted factor cachectinNature, 1985
- An endothelial cell-dependent pathway of coagulation.Proceedings of the National Academy of Sciences of the United States of America, 1985
- Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells.The Journal of Experimental Medicine, 1984
- Natural anticoagulant mechanisms.JCI Insight, 1984
- Protein C.1984
- Purification and characterization of bovine tissue factor.Online Journal of Public Health Informatics, 1981
- A factor X-activating cysteine protease from malignant tissue.JCI Insight, 1981