Human protein C receptor is present primarily on endothelium of large blood vessels: implications for the control of the protein C pathway.
Human protein C receptor is present primarily on endothelium of large blood vessels: implications for the control of the protein C pathway.
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DOI：
10.1161/01.cir.96.10.3633
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发表时间：
1997-11
期刊：
影响因子：
37.8
通讯作者：
Z. Laszik;A. Mitro;F. Taylor;G. Ferrell;C. Esmon
中科院分区：
文献类型：
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作者：
Z. Laszik;A. Mitro;F. Taylor;G. Ferrell;C. Esmon
背景蛋白C抗凝途径对止血控制至关重要。血栓调节蛋白和一种新发现的蛋白C/活化蛋白C受体EPCR都存在于内皮细胞上。EPCR通过凝血酶-血栓调节蛋白复合物增强蛋白C的活化。方法与结果为了更好地了解血栓调节蛋白与EPCR的关系，我们用免疫组织化学方法比较了这两种受体的细胞特异性和组织分布。EPCR表达几乎只在人和狒狒组织的内皮上检测到。在大多数器官中，EPCR在所有动脉和静脉、大多数小动脉和一些毛细血管后小静脉的内皮上表达相对较强。毛细血管内皮细胞的EPCR染色通常为阴性。相反，血栓调节蛋白在大血管和毛细血管内皮中均以高浓度检测到。血栓调节蛋白和EPCR在脑毛细血管中表达均较弱。肝血窦是仅有的毛细血管，其中EPCR以中等水平表达，血栓调节蛋白较低。EPCR和血栓调节蛋白均表达于肾髓质的直小血管内皮、淋巴结被膜下窦和髓窦以及肾上腺内的一些毛细血管。即使在这些器官中，大多数毛细血管也是EPCR阴性或染色较弱。结论EPCR可能在增强大血管蛋白C活化中起重要作用。动脉血管中存在高水平的EPCR可能有助于解释为什么部分蛋白C缺乏是动脉血栓形成的一个弱危险因素。
BACKGROUND The protein C anticoagulant pathway is critical to the control of hemostasis. Thrombomodulin and a newly identified receptor for protein C/activated protein C, EPCR, are both present on endothelium. EPCR augments activation of protein C by the thrombin-thrombomodulin complex. METHODS AND RESULTS To gain a better understanding of the relationship between thrombomodulin and EPCR, we compared the cellular specificity and tissue distributions of these two receptors by using immunohistochemistry. EPCR expression was detected almost exclusively on endothelium in human and baboon tissues. In most organs, EPCR was expressed relatively intensely on the endothelium of all arteries and veins, most arterioles, and some postcapillary venules. EPCR staining was usually negative on capillary endothelial cells. In contrast, thrombomodulin was detected at high concentrations in both large vessels and capillary endothelium. Both thrombomodulin and EPCR were expressed poorly on brain capillaries. The liver sinusoids were the only capillaries in which EPCR was expressed at moderate levels and thrombomodulin was low. EPCR and thrombomodulin were both expressed on the endothelium of vasa recta in the renal medulla, the lymph node subcapsular and medullary sinuses, and some capillaries within the adrenal gland. Even in these organs the majority of capillaries were EPCR negative or stained weakly. CONCLUSIONS These studies suggest that EPCR may be important in enhancing protein C activation on large vessels. The presence of high levels of EPCR on arterial vessels may help explain why partial protein C deficiency is a weak risk factor for arterial thrombosis.