Protein C pathway in sepsis
Protein C pathway in sepsis
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DOI：
10.1080/078538902321117823
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发表时间：
2002-01-01
影响因子：
4.4
通讯作者：
Esmon, CT
中科院分区：
文献类型：
--
作者：
Esmon, CT
本章的目的是提供一个简短的回顾蛋白C途径的生物学和一些功能的途径，使其独特的定位，以控制微血管凝血和控制急性炎症反应。活化的蛋白C通过灭活因子Va和VIIIa作为抗血栓形成剂起作用。它对预防微血管血栓形成特别有效。血小板可为活化蛋白C作为抗血栓药物提供安全范围。血浆中约25%的因子VNa包含在血小板内，因此对活化蛋白C的时间依赖性失活具有抗性。此外，与血小板表面结合的因子Va对活化蛋白C的失活具有相对抗性。活化蛋白C还通过抑制纤溶酶原激活物抑制物1促进凝块溶解。玻连蛋白显著加速了这一过程。炎性细胞因子如肿瘤坏死因子α（TNF α）和白细胞介素-1 β（IL-1 β）下调蛋白C活化复合物的两个关键组分，血栓调节蛋白和内皮细胞蛋白C受体，导致蛋白C活化降低。活化的蛋白C又在几种动物模型中和体外显示出抑制响应于内毒素的TNF产生。这种抑制似乎是由于减少核因子κ B（NF κ B）的表达和核转位。活化蛋白C已被证明可以降低严重脓毒症的死亡率。这种减少可能是由于D-二聚体减少所证明的抗凝作用和白细胞介素6减少所证明的炎症作用。
The goals of this chapter are to provide a brief review of the biology of the protein C pathway and some of the features of the pathway that make it uniquely positioned to control microvascular coagulation and control the acute inflammatory response. Activated protein C works as an antithrombotic agent by inactivating factors Va and Villa. It Is particularly effective at preventing microvascular thrombosis. Platelets may provide a margin of safety for activated protein C as an antithrombotic. Approximately 25% of the factor VNa in plasma is contained within the platelet and hence resistant to time dependent inactivation by activated protein C. In addition, factor Va bound to the platelet surface is relatively resistant to inactivation by activated protein C. Activated protein C also facilitates clot lysis by inhibiting plasminogen activator inhibitor 1. a process that is accelerated markedly by vitronectin. Inflammatory cytokines like tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) downregulate two key components of the protein C activation complex, thrombomodulin and the endothelial cell protein C receptor resulting in decreased protein C activation. Activated protein C in turn has been shown in several animal models and in vitro to inhibit TNF elaboration in response to endotoxin. This inhibition appears to be due to diminished nuclear factor kappaB (NF kappaB) expression and nuclear translocation. Activated protein C has been shown to reduce the rate of death due to severe sepsis. This reduction may be due to both the anticoagulant effects as demonstrated by a reduction in D-dimer and inflammatory effects as demonstrated by a reduction in interieukin 6.