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J Exp Med. Mar 1, 1986; 163(3): 740–745.
PMCID: PMC2188058

Modulation of endothelial cell hemostatic properties by tumor necrosis factor

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Rosenberg RD, Rosenberg JS. Natural anticoagulant mechanisms. J Clin Invest. 1984 Jul;74(1):1–6. [PMC free article] [PubMed]
  • Stern D, Nawroth P, Handley D, Kisiel W. An endothelial cell-dependent pathway of coagulation. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2523–2527. [PMC free article] [PubMed]
  • Beutler B, Greenwald D, Hulmes JD, Chang M, Pan YC, Mathison J, Ulevitch R, Cerami A. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature. 1985 Aug 8;316(6028):552–554. [PubMed]
  • Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. [PubMed]
  • Stern DM, Bank I, Nawroth PP, Cassimeris J, Kisiel W, Fenton JW, 2nd, Dinarello C, Chess L, Jaffe EA. Self-regulation of procoagulant events on the endothelial cell surface. J Exp Med. 1985 Oct 1;162(4):1223–1235. [PMC free article] [PubMed]
  • Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20;312(5996):724–729. [PubMed]
  • Nawroth PP, Stern DM, Kisiel W, Bach R. Cellular requirements for tissue factor generation by bovine aortic endothelial cells in culture. Thromb Res. 1985 Dec 1;40(5):677–691. [PubMed]
  • Bach R, Nemerson Y, Konigsberg W. Purification and characterization of bovine tissue factor. J Biol Chem. 1981 Aug 25;256(16):8324–8331. [PubMed]
  • Gordon SG, Cross BA. A factor X-activating cysteine protease from malignant tissue. J Clin Invest. 1981 Jun;67(6):1665–1671. [PMC free article] [PubMed]
  • Bevilacqua MP, Pober JS, Majeau GR, Cotran RS, Gimbrone MA., Jr Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med. 1984 Aug 1;160(2):618–623. [PMC free article] [PubMed]
  • Esmon CT. Protein C. Prog Hemost Thromb. 1984;7:25–54. [PubMed]

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