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Blood, 15 March 2001, Vol. 97, No. 6, pp. 1685-1688
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Endothelial cell protein C receptor plays an important role
in protein C activation in vivo
Fletcher B. Taylor Jr,
Glenn T. Peer,
Marion S. Lockhart,
Gary Ferrell, and
Charles T. Esmon
From the Cardiovascular Biology Research Program,
Oklahoma Medical Research Foundation; Departments of Pathology and
Biochemistry and Molecular Biology, University of Oklahoma Health
Sciences Center; and Howard Hughes Medical Institute, Oklahoma City,
Oklahoma.
Endothelial cell protein C receptor (EPCR) augments protein C
activation by the thrombin-thrombomodulin complex about 5-fold in
vitro. Augmentation is EPCR concentration dependent even when the EPCR
concentration is in excess of the thrombomodulin. EPCR is expressed
preferentially on large blood vessel endothelium, raising questions
about the importance of protein C-EPCR interaction for augmenting
systemic protein C activation. In these studies, this question was
addressed directly by infusing thrombin into baboons in the presence or
absence of a monoclonal antibody to EPCR that blocks protein C binding.
Activated protein C levels were then measured directly by capturing the
enzyme on a monoclonal antibody and assaying with chromogenic
substrate. Blocking protein C-EPCR interaction resulted in about an
88% decrease in circulating activated protein C levels generated in
response to thrombin infusion. Leukocyte changes, fibrinogen
consumption, fibrin degradation products, and vital signs were similar
between the animals infused with thrombin alone and those infused with
thrombin and the anti-EPCR antibody. The results indicate that EPCR
plays a major role in protein C activation and suggest that defects in
the EPCR gene might contribute to increased risk of thrombosis.

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