Regulation mechanism for inflammation mediated by endothelial cell protein C receptor

内皮细胞蛋白C受体(EPCR)是一种能与蛋白C特异结合的1型跨膜蛋白。我们建立了针对该分子的单抗，证明了在生理条件下蛋白C的激活需要EPCR。我们还发现，结合功能不限于酶原形式。激活的蛋白C(APC)以与蛋白C相同的方式与EPCR结合，我们检测了EPCR在癌细胞中的表达。APC与EPCR在癌细胞上形成的复合体可能通过催化基质金属蛋白水解酶的活性而促进肿瘤的进展。我们还发现了该分子在角质形成细胞和微粒上的表达。APC对内毒素休克有一定的治疗作用。脂多糖是致病因子，主要由Toll样受体4和MD-2的细胞表面复合体介导，可诱导多种细胞反应。内毒素需要被内毒素结合蛋白和CD14处理，才能被细胞表面受体复合体识别。为了分析APC/EPCR复合体对内毒素信号通路的影响，我们制备了这些分子的重组蛋白。我们将尝试分析凝血和炎症之间相互作用的分子机制。

The endothelial cell protein C receptor (EPCR) is a type 1 transmembrane protein, which is capable of specific binding of protein C. We established monoclonal antibodies against the molecule, and demonstrated that EPCR was required for protein C activation under the physiological conditions. We also found that the binding function was not restricted to the zymogen form. Activated protein C (APC) bound to EPCR in the same manner as protein C. We detected EPCR expression in cancer cells. Complex formation of APC with EPCR on cancer cells may contribute to progression of cancer via catalytic activity to matrix metaroproteases. We also found the expression of the molecule on keratinocytes and microparticles. They may contribute to regulation of inflammation.It has been demonstrated that APC was useful for therapy of endotoxin shock. Lipopolysaccharide (LPS) is the causative agent, and is known to induce various cell responses mainly mediated by the cell surface complex of Toll-like receptor 4 and MD-2. LPS needs to be processed by LPS-binding protein and CD14 to be recognized by the cell surface receptor complex. To analyze how APC/EPCR complex affects to the LPS-signaling pathway, we prepared recombinant proteins of these molecules. We will try to analyze molecular mechanisms of cross talking between blood coagulation and inflammation.