The endothelial cell protein C receptor (EPCR) functions as a primary receptor for protein C activation on endothelial cells in arteries, veins, and capillaries

Plasma protein C functions as an anticoagulant when it is converted to the active form of serine protease. Protein C activation has been found to be m ediated by the endothelial cell surface thrombin/ thrombomodulin (TM) compl ex. In addition, we recently identified the endothelial cell protein C/acti vated protein C receptor (EPCR) which is capable of high-affinity binding f or protein C. In this study, we established monoclonal antibodies (mAbs) ag ainst EPCR including several function blocking antibodies. Immunohistochemi cal analysis using these mAbs demonstrated that EPCR is widely expressed in the endothelial cells of arteries, veins, and capillaries in the lung, hea rt, and skin. Function blocking anti-EPCR mAbs strongly inhibited protein C activation mediated by primary cultured arterial endothelial cells which e xpress abundant EPCR. Anti-EPCR mAbs also prevent protein C activation medi ated by microvascular endothelial cells. These results indicate that EPCR f unctions as an important regulator for the protein C pathway in various typ es of vessels. (C) 1999 Academic Press.