Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Taylor, F. B.
Right arrow Articles by Esmon, C. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Taylor, F. B., Jr
Right arrow Articles by Esmon, C. T.
Related Collections
Right arrow Hemostasis, Thrombosis, and Vascular Biology
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

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.

© 2001 by The American Society of Hematology.
 

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. H. Finigan, A. Boueiz, E. Wilkinson, R. Damico, J. Skirball, H. H. Pae, M. Damarla, E. Hasan, D. B. Pearse, S. P. Reddy, et al.
Activated protein C protects against ventilator-induced pulmonary capillary leak
Am J Physiol Lung Cell Mol Physiol, June 1, 2009; 296(6): L1002 - L1011.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
F. Niessen, C. Furlan-Freguia, J. A. Fernandez, L. O. Mosnier, F. J. Castellino, H. Weiler, H. Rosen, J. H. Griffin, and W. Ruf
Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality
Blood, March 19, 2009; 113(12): 2859 - 2866.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
B. Saposnik, E. Lesteven, A. Lokajczyk, C. T. Esmon, M. Aiach, and S. Gandrille
Alternative mRNA is favored by the A3 haplotype of the EPCR gene PROCR and generates a novel soluble form of EPCR in plasma
Blood, April 1, 2008; 111(7): 3442 - 3451.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Gruber, U. M. Marzec, L. Bush, E. Di Cera, J. A. Fernandez, M. A. Berny, E. I. Tucker, O. J. T. McCarty, J. H. Griffin, and S. R. Hanson
Relative antithrombotic and antihemostatic effects of protein C activator versus low-molecular-weight heparin in primates
Blood, April 1, 2007; 109(9): 3733 - 3740.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
L. R. Mollica, J. T. B. Crawley, K. Liu, J. B. Rance, P. N. Cockerill, G. A. Follows, J.-R. Landry, D. J. Wells, and D. A. Lane
Role of a 5'-enhancer in the transcriptional regulation of the human endothelial cell protein C receptor gene
Blood, August 15, 2006; 108(4): 1251 - 1259.
[Abstract] [Full Text] [PDF]


Home page
StrokeHome page
D. Brenner, J. Labreuche, P.-J. Touboul, K. Schmidt-Petersen, O. Poirier, C. Perret, J. Schonfelder, C. Combadiere, M. Lathrop, F. Cambien, et al.
Cytokine Polymorphisms Associated With Carotid Intima-Media Thickness in Stroke Patients
Stroke, July 1, 2006; 37(7): 1691 - 1696.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
W. Li, X. Zheng, J.-M. Gu, G. L. Ferrell, M. Brady, N. L. Esmon, and C. T. Esmon
Extraembryonic expression of EPCR is essential for embryonic viability
Blood, October 15, 2005; 106(8): 2716 - 2722.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
B. Dahlback and B. O. Villoutreix
Regulation of Blood Coagulation by the Protein C Anticoagulant Pathway: Novel Insights Into Structure-Function Relationships and Molecular Recognition
Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1311 - 1320.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
J. H. Finigan, S. M. Dudek, P. A. Singleton, E. T. Chiang, J. R. Jacobson, S. M. Camp, S. Q. Ye, and J. G. N. Garcia
Activated Protein C Mediates Novel Lung Endothelial Barrier Enhancement: ROLE OF SPHINGOSINE 1-PHOSPHATE RECEPTOR TRANSACTIVATION
J. Biol. Chem., April 29, 2005; 280(17): 17286 - 17293.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
M. Levi, T. van der Poll, and H. R. Buller
Bidirectional Relation Between Inflammation and Coagulation
Circulation, June 8, 2004; 109(22): 2698 - 2704.
[Full Text] [PDF]


Home page
BloodHome page
B. Saposnik, J.-L. Reny, P. Gaussem, J. Emmerich, M. Aiach, and S. Gandrille
A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis
Blood, February 15, 2004; 103(4): 1311 - 1318.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
B. A. Kerlin, S. B. Yan, B. H. Isermann, J. T. Brandt, R. Sood, B. R. Basson, D. E. Joyce, H. Weiler, and J.-F. Dhainaut
Survival advantage associated with heterozygous factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia
Blood, November 1, 2003; 102(9): 3085 - 3092.
[Abstract] [Full Text] [PDF]


Home page
ChestHome page
C. T. Esmon
The Protein C Pathway
Chest, September 1, 2003; 124(3_suppl): 26S - 32S.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Slungaard, J. A. Fernandez, J. H. Griffin, N. S. Key, J. R. Long, D. J. Piegors, and S. R. Lentz
Platelet factor 4 enhances generation of activated protein C in vitro and in vivo
Blood, July 1, 2003; 102(1): 146 - 151.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
J. B. Rance, G. A. Follows, P. N. Cockerill, C. Bonifer, D. A. Lane, and R. E. Simmonds
Regulation of the human endothelial cell protein C receptor gene promoter by multiple Sp1 binding sites
Blood, June 1, 2003; 101(11): 4393 - 4401.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
S. R. Lentz
Thrombosis of Vein Grafts: Wall Tension Restrains Thrombomodulin Expression
Circ. Res., January 10, 2003; 92(1): 12 - 13.
[Full Text] [PDF]


Home page
BloodHome page
M. J. A. Simmelink, P. G. de Groot, R. H. W. M. Derksen, J. A. Fernandez, and J. H. Griffin
Oral anticoagulation reduces activated protein C less than protein C and other vitamin K-dependent clotting factors
Blood, December 1, 2002; 100(12): 4232 - 4233.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
J.-M. Gu, J. T. B. Crawley, G. Ferrell, F. Zhang, W. Li, N. L. Esmon, and C. T. Esmon
Disruption of the Endothelial Cell Protein C Receptor Gene in Mice Causes Placental Thrombosis and Early Embryonic Lethality
J. Biol. Chem., November 1, 2002; 277(45): 43335 - 43343.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
S. R. Lentz, F. J. Miller Jr, D. J. Piegors, R. A. Erger, J. A. Fernandez, J. H. Griffin, and D. D. Heistad
Anticoagulant Responses to Thrombin Are Enhanced During Regression of Atherosclerosis in Monkeys
Circulation, August 13, 2002; 106(7): 842 - 846.
[Abstract] [Full Text] [PDF]



 click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020