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

DOI 10.1172/jci119548PMC PMC508205

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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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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
ORCID: Kurosawa, S
Stearns-Kurosawa, D J
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1997-07-15
Volume: 100
Issue: 2
Pages: 411-418
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci119548
PMC: PMC508205
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: bronze
doi.org
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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Identification of functional endothelial protein C receptor in human plasma.

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