Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA.
Crit Care Med. 2010 Feb;38(2 Suppl):S18-25. doi: 10.1097/CCM.0b013e3181c9cbb5.
To review new findings about the function of the protein C system during inflammation and coagulation.
Coagulation proteases and their cofactors modify the outcome of severe inflammation by engaging signaling-competent cell surface receptors. The central effector protease of the protein C pathway, activated protein C, interacts with the endothelial cell protein C receptor, protease-activated receptors, and other receptors to exert multiple effects on hemostasis and immune cell function. Thrombomodulin controls the complement arm of the innate immune system in a thrombin-dependent manner through activation of the thrombin activatable inhibitor of fibrinolysis, and in a thrombin-independent, constitutive manner via its lectin-like extracellular domain; and inhibits the inflammatory effects of high-mobility box group 1 protein. Protein S not only suppresses coagulation as an enhancing cofactor for the coagulation inhibitors activated protein C and tissue factor pathway inhibitor but also is also a physiologic ligand for the Tyro/axl/Mer-family of receptor tyrosine kinases that mediate an anti-inflammatory regulatory loop of dendritic cell and monocyte inflammatory function.
The immune-regulatory capacity of the protein C pathway and its individual components emerge as the dominant action of this pathway in the setting of severe inflammation.
综述蛋白 C 系统在炎症和凝血过程中的新功能发现。
凝血蛋白酶及其辅因子通过与信号转导有效细胞表面受体相互作用，修饰严重炎症的结局。蛋白 C 途径的中心效应蛋白酶，活化蛋白 C，通过与内皮细胞蛋白 C 受体、蛋白酶激活受体以及其他受体相互作用，对止血和免疫细胞功能发挥多种作用。血栓调节蛋白通过激活纤维蛋白溶解酶原激活物抑制物，以依赖凝血酶的方式，以及通过其凝集素样细胞外结构域，以非依赖凝血酶的组成型方式，控制补体系统固有免疫的效应臂；并抑制高迁移率族蛋白 1 的炎症作用。蛋白 S 不仅作为凝血抑制剂活化蛋白 C 和组织因子途径抑制物的增强辅因子抑制凝血，而且还是 Tyro/axl/Mer 家族受体酪氨酸激酶的生理性配体，介导树突状细胞和单核细胞炎症功能的抗炎调节环。
蛋白 C 途径及其单个成分的免疫调节能力是该途径在严重炎症情况下的主要作用。
