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首页> 外文期刊>British Journal of Haematology >The endothelial cells downregulate the generation of factor VIIa through EPCR binding.
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The endothelial cells downregulate the generation of factor VIIa through EPCR binding.

机译：内皮细胞通过EPCR结合下调因子VIIa的产生。

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Traces of activated factor VII (FVIIa) are required to maintain haemostasis. Activated factor X (FXa) is the main activator of FVII in the absence of tissue factor. However, little is known about how this mechanism is regulated. We and others reported the interaction between FVII and the endothelial cell protein C receptor (EPCR). We have analysed the role of EPCR in the FXa-dependent FVIIa generation. Activation was performed on the surface of human aortic endothelial cells in the presence or absence of a blocking anti-EPCR monoclonal antibody (mAb). Western-blot analyses revealed that FVII activation was increased twofold upon EPCR blocking. Kinetic analyses revealed that blocking doubled the catalytic efficiency for activation. Protein C was unable to mimic the effect of the anti-EPCR mAb on activation. Surface plasmon resonance experiments revealed that binding of EPCR and phospholipids to FVII were mutually exclusive. The 50% inhibitory concentration value for phospholipids to reduce the binding of FVIIa to EPCR was 57.67 +/- 0.11 micromol/l. Immunofluorescence experiments showed that EPCR and phosphatidylserine are located at different regions of the cell surface. We propose that EPCR downregulates FVII activation by moving it from phosphatidylserine-rich regions. In summary, this study described a new anticoagulant role for EPCR.
机译：需要微量的活化因子VII（FVIIa）来维持止血。在没有组织因子的情况下，活化因子X（FXa）是FVII的主要活化剂。但是，关于如何调节这种机制知之甚少。我们和其他人报道了FVII与内皮细胞蛋白C受体（EPCR）之间的相互作用。我们已经分析了EPCR在依赖FXa的FVIIa世代中的作用。在存在或不存在封闭抗EPCR单克隆抗体（mAb）的情况下，在人主动脉内皮细胞表面进行激活。 Western印迹分析显示，FVII激活在EPCR阻断后增加了两倍。动力学分析表明，封闭使活化的催化效率提高了一倍。蛋白C无法模拟抗EPCR mAb对激活的影响。表面等离子体共振实验表明，EPCR和磷脂与FVII的结合是互斥的。降低FVIIa与EPCR结合的磷脂的50％抑制浓度值为57.67 +/- 0.11 micromol / l。免疫荧光实验表明，EPCR和磷脂酰丝氨酸位于细胞表面的不同区域。我们建议EPCR通过从富含磷脂酰丝氨酸的区域移动FVII来下调FVII的激活。总而言之，这项研究描述了EPCR的新抗凝作用。

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