INTERLEUKIN-1 INDUCES ENDOTHELIAL-CELL PROCOAGULANT WHILE SUPPRESSING CELL-SURFACE ANTICOAGULANT ACTIVITY
INTERLEUKIN-1 INDUCES ENDOTHELIAL-CELL PROCOAGULANT WHILE SUPPRESSING CELL-SURFACE ANTICOAGULANT ACTIVITY
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DOI：
10.1073/pnas.83.10.3460
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发表时间：
1986-05-01
影响因子：
11.1
通讯作者：
STERN, DM
中科院分区：
文献类型：
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作者：
NAWROTH, PP;HANDLEY, DA;STERN, DM
以往的研究表明，内皮细胞积极参与抗凝和促凝反应。虽然抗凝机制在静止内皮细胞表面占主导地位，但扰动的内皮细胞可以通过协同诱导促凝活性和抑制抗凝机制来促进凝血。将纯化的重组白细胞介素1静脉输注到家兔体内，随后研究了天然主动脉内皮的凝血特性。白细胞介素1输注导致促凝血辅助因子组织因子的时间和剂量依赖性诱导，同时阻断蛋白C抗凝途径。输注后3-5小时，组织因子活性增加> 10倍，而内皮细胞依赖性凝血酶介导的蛋白C活化降低72%，功能性活化蛋白C-蛋白S复合物在血管表面上的组装降低> 90%。扫描电子显微镜显示大动脉纤维蛋白链与管腔内皮细胞表面密切相关，倾向于分叉。白细胞介素1是炎症反应的介质，可以单向地改变内皮上促凝血和抗凝反应的平衡，有利于凝块形成。因此，扰动内皮的表面可以提供模板，促进血栓前状态的发展，并提供血栓形成早期阶段的模型。
Previous studies demonstrated that endothelial cells participate actively in both anticoagulant and procoagulant reactions. Although anticoagulant mechanisms predominant on the surface of quiesecnet 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 assembly of functional activated protein C-protein S complex on the vessel surface was decreased by > 90%. Scanning electron microscopy of major arteries demostrated 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 prethrombic state, and provides a model for the early stages of thrombosis.