Guitton Christophe, Gérard Nathalie, Quillard Thibaut, Charreau Béatrice
INSERM UMR643, Institut de Transplantation et de Recherche en Transplantation, Nantes, France.
J Vasc Res. 2011;48(4):336-46. doi: 10.1159/000322582. Epub 2011 Jan 27.
The endothelial cell (EC) protein C receptor (EPCR) negatively regulates coagulation and inflammation. Factors and mechanisms regulating the expression of cell-bound EPCR and the release of soluble (s) EPCR are still unclear.
We investigated the reciprocal regulation of membrane-bound and sEPCR upon inflammation using primary cultures of vascular EC. The impact of 2 parameters, gender and EPCR gene A3 haplotype, on sEPCR plasma basal level and endothelial expression was examined by Elisa and flow cytometry.
Exposure of EC to tumor necrosis factor α causes a rapid downregulation of membrane-associated EPCR expression without affecting markedly the spontaneous release of sEPCR by EC. In a cohort of 100 healthy donors, we show that males express significantly higher basal sEPCR in plasma than females (194 ± 12 vs. 145 ± 9 ng/ml, respectively, p<0.01). Both gender and EPCR A3 haplotype affect sEPCR plasma levels but have no apparent effect on EPCR expression by EC. No quantitative correlation between cellular expression and circulating blood sEPCR was observed, suggesting that endothelial expression may not reflect the plasma level.
Male gender is another parameter with A3 haplotype associated with elevated sEPCR levels in blood, and both parameters may contribute to selective regulatory mechanisms of EPCR release upon inflammation.
内皮细胞（EC）蛋白C受体（EPCR）对凝血和炎症起负调节作用。调节细胞结合型EPCR表达及可溶性（s）EPCR释放的因素和机制仍不清楚。
我们利用血管内皮细胞原代培养研究了炎症状态下膜结合型和sEPCR的相互调节。通过酶联免疫吸附测定（ELISA）和流式细胞术检测性别和EPCR基因A3单倍型这两个参数对sEPCR血浆基础水平及内皮表达的影响。
内皮细胞暴露于肿瘤坏死因子α会导致膜相关EPCR表达迅速下调，而对内皮细胞sEPCR的自发释放无明显影响。在100名健康供者队列中，我们发现男性血浆中基础sEPCR表达显著高于女性（分别为194±12与145±9 ng/ml，p<0.01）。性别和EPCR A3单倍型均影响sEPCR血浆水平，但对内皮细胞EPCR表达无明显影响。未观察到细胞表达与循环血中sEPCR之间的定量相关性，提示内皮表达可能无法反映血浆水平。
男性是与血液中sEPCR水平升高相关的另一个参数，与A3单倍型一样，这两个参数可能共同促成炎症时EPCR释放的选择性调节机制。
