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首页> 外文期刊>Critical care : >New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated).
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New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated).

机译：蛋白质C途径的新见解：对drotrecogin alfa（活化）的生物活性的潜在影响。

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It has been hypothesized that the protein C pathway is a pivotal link between the inflammation and coagulation cascades. The demonstration that a survival benefit is associated with administration of drotrecogin alfa (activated) (recombinant human activated protein C [APC]) in severe sepsis patients has provided new insights into the protein C pathway. APC was originally identified based on its antithrombotic properties, which result from the inhibition of activated Factors V and VIII. In the early 1990s, any potential anti-inflammatory properties of APC were thought to relate primarily to its inhibition of thrombin generation. However, the mid-1990s saw the identification of the endothelial protein C receptor (EPCR), which has subsequently been shown to be neither endothelial specific nor protein C specific, but has a primary function as a cofactor for enhancing the generation of APC or behaving as an APC receptor. Thus, the potential biologic activities of APC can be classed into two categories related either to the limiting of thrombin generation or to cellular effects initiated by binding to the EPCR. Intracellular signaling initiated by binding of APC to its receptor appears to be mediated by interaction with an adjacent protease-activated receptor (PAR), or by indirect activation of the sphingosine 1-phosphate pathway. Based mostly on in vitro studies, binding of APC to its receptor on endothelial cells leads to a decrease in thrombin-induced endothelial permeability injury, while such binding on blood cells, epithelial cells, and neurons has been shown to inhibit chemotaxis, be anti-apoptotic, and be neuroprotective, respectively. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study, drotrecogin alfa (activated) was associated with improved cardiovascular function, respiratory function, and a prevention of hematologic dysfunction. This article discusses the way in which the interactions of APC may alter the microcirculation.
机译：假设蛋白C通路是炎症和凝血级联反应之间的关键环节。在严重的脓毒症患者中，生存获益与使用drotrecogin alfa（激活的）（重组人激活的蛋白C [APC]）相关的证明为蛋白C途径提供了新的见解。 APC最初是基于其抗血栓形成特性而鉴定的，该特性是由抑制活化的因子V和VIII引起的。在1990年代初期，人们认为APC的任何潜在抗炎特性主要与抑制凝血酶的产生有关。然而，在1990年代中期发现了内皮蛋白C受体（EPCR）的鉴定，随后证明它既不是内皮特异性蛋白也不是蛋白C特异性蛋白，但主要起辅助作用，可增强APC的生成或表现作为APC受体。因此，APC的潜在生物活性可以分为两类，分别与凝血酶的产生限制或与结合EPCR引发的细胞效应有关。 APC与其受体结合引发的细胞内信号传导似乎是通过与邻近的蛋白酶激活受体（PAR）相互作用或间接激活鞘氨醇1-磷酸途径来介导的。主要基于体外研究，APC与其内皮细胞受体的结合可导致凝血酶诱导的内皮通透性损伤的减少，而这种对血细胞，上皮细胞和神经元的结合已显示出抑制趋化性的作用，这是抗-分别具有凋亡和神经保护作用。在严重脓毒症的全球重组人类活化蛋白C评估（PROWESS）研究中，drotrecogin alfa（活化）与改善的心血管功能，呼吸功能和预防血液功能障碍有关。本文讨论了APC相互作用可能改变微循环的方式。

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