Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity

P. P. Nawroth, D. A. Handley, C. T. Esmon, David Stern

Research output: Contribution to journalArticle

431 Citations (Scopus)

Abstract

Previous studies demonstrated that endothelial cells participate actively in both anticoagulant and procoagulant reactions. Although anticoagulant mechanisms predominate on the surface of quiescent endothelial cells, perturbed endothelial cells can promote coagulation through the coordinated induction of procoagulant activity and suppression of anticoagulant mechanisms. Purified recombinant interleukin 1 was infused intravenously into rabbits and coagulant properties of the native aortic endothelium were subsequently studied. Interleukin 1 infusion resulted in a time and dose-dependent induction of the procoagulant cofactor tissue factor, while concomitantly blocking the protein C anticoagulant pathway. Tissue factor activity increased > 10-fold by 3-5 hr after the infusion, while endothelial cell-dependent thrombin-mediated protein C activation decreased by 72% and asssembly of functional activated protein C-protein S complex on the vessel surface was decreased by > 90%. Scanning electron microscopy of major arteries demonstrated fibrin strands closely associated with the luminal endothelial cell surface with a predilection for bifurcations. Interleukin 1, a mediator of the inflammatory response, can shift the balance of procoagulant and anticoagulant reactions on the endothelium unidirectionally favoring clot formation. The surface of perturbed endothelium can thus provide a template, facilitating the development of a prethrombotic state, and provides a model for the early stages of thrombosis.

Original languageEnglish (US)
Pages (from-to)3460-3464
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number10
DOIs
StatePublished - Jan 1 1986

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Interleukin-1
Anticoagulants
Endothelial Cells
Protein C
Endothelium
Thromboplastin
Coagulants
Protein S
Fibrin
Thrombin
Electron Scanning Microscopy
Thrombosis
Arteries
Rabbits

All Science Journal Classification (ASJC) codes

  • General

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Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. / Nawroth, P. P.; Handley, D. A.; Esmon, C. T.; Stern, David.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 83, No. 10, 01.01.1986, p. 3460-3464.

Research output: Contribution to journalArticle

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abstract = "Previous studies demonstrated that endothelial cells participate actively in both anticoagulant and procoagulant reactions. Although anticoagulant mechanisms predominate on the surface of quiescent endothelial cells, perturbed endothelial cells can promote coagulation through the coordinated induction of procoagulant activity and suppression of anticoagulant mechanisms. Purified recombinant interleukin 1 was infused intravenously into rabbits and coagulant properties of the native aortic endothelium were subsequently studied. Interleukin 1 infusion resulted in a time and dose-dependent induction of the procoagulant cofactor tissue factor, while concomitantly blocking the protein C anticoagulant pathway. Tissue factor activity increased > 10-fold by 3-5 hr after the infusion, while endothelial cell-dependent thrombin-mediated protein C activation decreased by 72{\%} and asssembly of functional activated protein C-protein S complex on the vessel surface was decreased by > 90{\%}. Scanning electron microscopy of major arteries demonstrated fibrin strands closely associated with the luminal endothelial cell surface with a predilection for bifurcations. Interleukin 1, a mediator of the inflammatory response, can shift the balance of procoagulant and anticoagulant reactions on the endothelium unidirectionally favoring clot formation. The surface of perturbed endothelium can thus provide a template, facilitating the development of a prethrombotic state, and provides a model for the early stages of thrombosis.",
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