Cited by 157Blood Coagulation and Thrombosis MechanismsComplement system in diseasesProtease and Inhibitor Mechanisms

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Identification of functional endothelial protein C receptor in human plasma.

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Kurosawa, S, Stearns-Kurosawa, D J, Hidari, N, Esmon, C T·1997·Journal of Clinical Investigation

Abstract

The endothelial cell protein C receptor (EPCR) binds protein C and facilitates activation by the thrombin-thrombomodulin complex. EPCR also binds activated protein C (APC) and inhibits APC anticoagulant activity. In this study, we detected a soluble form of EPCR in normal human plasma. Plasma EPCR appears to be approximately 43, 000 D, and circulates at approximately 100 ng/ml (98.4+/-27.8 ng/ml, n = 22). Plasma EPCR was purified from human citrated plasma using ion exchange, immunoaffinity, and protein C affinity chromatography. Flow cytometry experiments demonstrated that plasma EPCR bound APC with an affinity similar to that previously determined for recombinant soluble EPCR (Kdapp = 30 nM). Furthermore, plasma EPCR inhibited both protein C activation on an endothelial cell line and APC anticoagulant activity in a one-stage Factor Xa clotting assay. The physiological function of plasma EPCR is uncertain, but if the local concentrations are sufficiently high, particularly in disease states, the present data suggest that the soluble plasma EPCR could attenuate the membrane-bound EPCR augmentation of protein C activation and the anticoagulant function of APC.

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Crossref · 10.1172/jci119548

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Metadata

Authors
Kurosawa, S., Stearns-Kurosawa, D. J., Hidari, N., & Esmon, C. T.
Affiliations
  • Oklahoma Medical Research Foundation (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Esmon, C T
Venue
Journal of Clinical Investigation
Published
1997-07-15
Volume
100
Issue
2
Pages
411-418
ISSN
0021-9738 (ISSN-L)
OpenAlex
W1993601122
Cited by
154
References
50
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2017: 3 · 2016: 8 · 2015: 8 · 2014: 13 · 2013: 16 · 2012: 2
FWCI
3.66
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (P50 HL54502)
  • National Heart, Lung, and Blood Institute (P50HL054502, P01 HL54804, P50-HL54502, P01HL054804)
Topics
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
endothelial protein C receptor, soluble EPCR, activated protein C, protein C activation, anticoagulant activity, thrombin-thrombomodulin complex, plasma protein purification, endothelial cells
MeSH terms
Anticoagulants, Blood Coagulation, Blood Coagulation Factors, Cells, Cultured, Chromatography, Affinity, Endothelium, Vascular, Flow Cytometry, Humans, Protein Binding, Protein C, Receptors, Cell Surface, Recombinant Proteins, Solubility, Thrombin, Blotting, Western, Factor Xa, Thrombomodulin

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