Beretz A, Klein-Soyer C, Archipoff G, Camilla C, Brisson C, Freyssinet J M, Cazenave J P
INSERM U.311, Centre Régional de Transfusion Sanguine, Strasbourg, France.
Biorheology. 1990;27(3-4):455-60. doi: 10.3233/bir-1990-273-423.
Endothelial cells play an important role in the regulation of thrombosis. Normal resting (i.e. unstimulated) endothelial cells exhibit antithrombotic activity. This property is due to an active participation of endothelial cells in the inhibition of platelet adhesion and aggregation, in the inhibition of thrombin generation, in the direct inactivation of thrombin, and in clot lysis through the fibrinolytic system. When endothelial cells are stimulated by cytokines such as tumor necrosis factor (TNF) or interleukin 1 (IL-1), they may switch to an active procoagulant state. On the one hand, thrombin generation can be regulated on the endothelial cell surface by thrombomodulin, which allows the activation by thrombin of protein C which subsequently acquires and expresses potent anticoagulant properties. On the other hand, after activation, the same endothelial cell can express tissue factor on its surface, which will lead to the triggering of the coagulation cascade resulting in the generation of thrombin. TNF has been shown both to induce tissue factor gene expression and to suppress transcription of the thrombomodulin gene in endothelial cells. Many cytokines induce tissue factor gene expression and procoagulant activity in the monocyte/macrophage lineage; they also stimulate adhesion of leukocytes to endothelial cells. Cytokines such as IL-1 or TNF can thus be characterized as important intercellular messengers during the onset of coagulation. The role of these compounds can be schematized as: 1) agents of the stimulation of endothelial cells by leukocytes, 2) agents of stimulation of leukocytes by endothelial cells, 3) localization of the coagulation response through the initiation of endothelial cell-leukocyte interactions. Pharmacological modulation of these responses is possible along two pathways: 1) inhibition of the activation of endothelial cells or leukocytes responsible for cytokine release, 2) inhibition of the cytokine-induced cellular activation responsible for potentiation of procoagulant activity.
内皮细胞在血栓形成的调节中发挥着重要作用。正常静息（即未受刺激）的内皮细胞具有抗血栓活性。这一特性归因于内皮细胞积极参与抑制血小板黏附和聚集、抑制凝血酶生成、直接使凝血酶失活以及通过纤维蛋白溶解系统溶解血栓。当内皮细胞受到细胞因子如肿瘤坏死因子（TNF）或白细胞介素1（IL-1）刺激时，它们可能转变为活跃的促凝状态。一方面，凝血酶生成可在内皮细胞表面由血栓调节蛋白进行调节，血栓调节蛋白使凝血酶激活蛋白C，随后蛋白C获得并表现出强大的抗凝特性。另一方面，激活后，同一内皮细胞可在其表面表达组织因子，这将导致凝血级联反应的触发，从而产生凝血酶。已表明TNF既能诱导内皮细胞中组织因子基因表达，又能抑制血栓调节蛋白基因的转录。许多细胞因子在单核细胞/巨噬细胞谱系中诱导组织因子基因表达和促凝活性；它们还刺激白细胞与内皮细胞的黏附。因此，IL-1或TNF等细胞因子可被视为凝血开始过程中的重要细胞间信使。这些化合物的作用可概括为：1）白细胞刺激内皮细胞的介质；2）内皮细胞刺激白细胞的介质；3）通过启动内皮细胞-白细胞相互作用使凝血反应定位。沿着两条途径对这些反应进行药理调节是可能的：1）抑制负责细胞因子释放的内皮细胞或白细胞的激活；2）抑制细胞因子诱导的导致促凝活性增强的细胞激活。
