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J. Exp. Med.,
Volume 187, Number 7, April 6, 1998 1029-1035
By

From the * Department of Immunology and the Protein C is an important regulatory mechanism of blood coagulation. Protein C functions as
an anticoagulant when converted to the active serine protease form on the endothelial cell surface. Thrombomodulin (TM), an endothelial cell surface receptor specific for thrombin, has
been identified as an essential component for protein C activation. Although protein C can be
activated directly by the thrombin-TM complex, the conversion is known as a relatively low-affinity reaction. Therefore, protein C activation has been believed to occur only in microcirculation. On the other hand, we have identified and cloned a novel endothelial cell surface receptor (EPCR) that is capable of high-affinity binding of protein C and activated protein C. In
this study, we demonstrate the constitutive, endothelial cell-specific expression of EPCR in
vivo. Abundant expression was particularly detected in the aorta and large arteries. In vitro cultured, arterial endothelial cells were also found to express abundant EPCR and were capable of
promoting significant levels of protein C activation. EPCR was found to greatly accelerate protein C activation by examining functional activity in transfected cell lines expressing EPCR
and/or TM. EPCR decreased the dissociation constant and increased the maximum velocity
for protein C activation mediated by the thrombin-TM complex. By these mechanisms,
EPCR appears to enable significant levels of protein C activation in large vessels. These results
suggest that the protein C anticoagulation pathway is important for the regulation of blood coagulation not only in microvessels but also in large vessels.
Department of Pathology, Saga Medical School,
Nabeshima, Saga 849, Japan; and the § Applied Research Laboratory, The Chemo-Sero-Therapeutic
Research Institute, Shimizu, Kumamoto 860, Japan
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