Identification of functional endothelial protein C receptor in human plasma
Identification of functional endothelial protein C receptor in human plasma
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DOI：
10.1172/jci119548
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发表时间：
1997-07-15
影响因子：
15.9
通讯作者：
Esmon, CT
中科院分区：
文献类型：
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作者：
Kurosawa, S;StearnsKurosawa, DJ;Esmon, CT
内皮细胞蛋白C受体（EPCR）结合蛋白C并促进凝血酶-血栓调节蛋白复合物的活化，EPCR还结合活化蛋白C（APC）并抑制APC抗凝活性。在这项研究中，我们在正常人血浆中检测到可溶性形式的EPCR。血浆EPCR似乎与43，000 D相似，并以类似于100 ng/ml（98.4+/-27.8 ng/ml，n = 22）的浓度循环。使用离子交换、免疫亲和和蛋白C亲和色谱法从人柠檬酸盐血浆中纯化血浆EPCR。流式细胞术实验表明，血浆EPCR结合APC的亲和力与先前测定的重组可溶性EPCR（K-dapp = 30 nM）相似。此外，血浆EPCR抑制内皮细胞系上的蛋白C活化和一期Xa因子凝血测定中的APC抗凝活性。血浆EPCR的生理功能是不确定的，但如果局部浓度足够高，特别是在疾病状态下，目前的数据表明，可溶性血浆EPCR可以减弱膜-结合EPCR增强蛋白C活化和APC的抗凝功能。
The endothelial cell protein C receptor (EPCR) binds protein C and facilitates activation by the thrombin-thrombomodulin complex, EPCR also binds activated protein C (APC) and inhibits APC anticoagulant activity. In this study, we detected a soluble form of EPCR in normal human plasma. Plasma EPCR appears to be similar to 43,000 D, and circulates at similar to 100 ng/ml (98.4+/-27.8 ng/ml, n = 22), Plasma EPCR was purified from human citrated plasma using ion exchange, immunoaffinity, and protein C affinity chromatography. Flow cytometry experiments demonstrated that plasma EPCR bound APC with an affinity similar to that previously determined for recombinant soluble EPCR (K-dapp = 30 nM). Furthermore, plasma EPCR inhibited both protein C activation on an endothelial cell line and APC anticoagulant activity in a one-stage Factor Xa clotting assay, The physiological function of plasma EPCR is uncertain, but if the local concentrations are sufficiently high, particularly in disease states, the present data suggest that the soluble plasma EPCR could attenuate the membrane-bound EPCR augmentation of protein C activation and the anticoagulant function of APC.