|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1687-1693
Endotoxin and thrombin elevate rodent endothelial cell protein C
receptor mRNA levels and increase receptor shedding in vivo
Jian-Ming Gu,
Yasuhiro Katsuura,
Gary L. Ferrell,
Paula Grammas, and
Charles T. Esmon
From the Cardiovascular Biology Research Program, Oklahoma Medical
Research Foundation, Oklahoma City, Oklahoma; Pharmaceuticals
Development Research Laboratories, Teijin, Ltd, Tokyo, Japan; Howard
Hughes Medical Institute, Oklahoma City, Oklahoma; and the Departments
of Pathology and Biochemistry and Molecular Biology, University of
Oklahoma Health Science Center, Oklahoma City, Oklahoma.
The endothelial cell protein C receptor (EPCR) facilitates protein C
activation by the thrombin-thrombomodulin complex. Protein C activation
has been shown to be critical to the host defense against septic shock.
In cell culture, tumor necrosis factor- (TNF-) down-regulates
EPCR expression, raising the possibility that EPCR might be
down-regulated in septic shock. We examined EPCR mRNA and soluble EPCR
levels in mice and rats challenged with lethal dose 95 levels of
endotoxin. Toxic doses of TNF- failed to alter EPCR mRNA levels in
mice. Rather than EPCR mRNA levels falling in response to
endotoxin, as predicted from cell-culture experiments, they rose
approximately 3-fold 6 hours after exposure to endotoxin before
returning toward baseline levels at 24 hours after exposure. Soluble
EPCR levels rose approximately 4-fold. Infusion of hirudin, a
specific thrombin inhibitor, before endotoxin exposure almost
completely blocked the increase in EPCR mRNA and soluble EPCR.
Consistent with the idea that the responses were mediated by
thrombin, thrombin infusion (5 U/kg of body weight for 3 hours)
resulted in an approximately 2-fold increase in EPCR mRNA
and soluble EPCR. Incubation of rat endothelial cells with thrombin or
murine protease-activated receptor 1 agonist peptide resulted in a
2-fold increase in EPCR mRNA. These results indicate that thrombin
plays a major role in up-regulating EPCR mRNA and shedding in vivo.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Song, X. Ye, H. Xu, and S. F. Liu
Activation of endothelial intrinsic NF-{kappa}B pathway impairs protein C anticoagulation mechanism and promotes coagulation in endotoxemic mice
Blood,
September 17, 2009;
114(12):
2521 - 2529.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M R Looney, C T Esmon, and M A Matthay
Role of coagulation pathways and treatment with activated protein C in hyperoxic lung injury
Thorax,
February 1, 2009;
64(2):
114 - 120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Borgel, C. Bornstain, P. H. Reitsma, N. Lerolle, S. Gandrille, F. Dali-Ali, C. T. Esmon, J.-Y. Fagon, M. Aiach, and J.-L. Diehl
A Comparative Study of the Protein C Pathway in Septic and Nonseptic Patients with Organ Failure
Am. J. Respir. Crit. Care Med.,
November 1, 2007;
176(9):
878 - 885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Wang, J. A. Bastarache, N. Wickersham, X. Fang, M. A. Matthay, and L. B. Ware
Novel Role of the Human Alveolar Epithelium in Regulating Intra-Alveolar Coagulation
Am. J. Respir. Cell Mol. Biol.,
April 1, 2007;
36(4):
497 - 503.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. C. Aird
Phenotypic Heterogeneity of the Endothelium: I. Structure, Function, and Mechanisms
Circ. Res.,
February 2, 2007;
100(2):
158 - 173.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zheng, W. Li, J.-M. Gu, D. Qu, G. L. Ferrell, N. L. Esmon, and C. T. Esmon
Effects of membrane and soluble EPCR on the hemostatic balance and endotoxemia in mice
Blood,
February 1, 2007;
109(3):
1003 - 1009.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Ganopolsky and F. J. Castellino
A Protein C Deficiency Exacerbates Inflammatory and Hypotensive Responses in Mice During Polymicrobial Sepsis in a Cecal Ligation and Puncture Model
Am. J. Pathol.,
October 1, 2004;
165(4):
1433 - 1446.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. V. de Wouwer, D. Collen, and E. M. Conway
Thrombomodulin-Protein C-EPCR System: Integrated to Regulate Coagulation and Inflammation
Arterioscler Thromb Vasc Biol,
August 1, 2004;
24(8):
1374 - 1383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
R. Pawlinski, B. Pedersen, G. Schabbauer, M. Tencati, T. Holscher, W. Boisvert, P. Andrade-Gordon, R. D. Frank, and N. Mackman
Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia
Blood,
February 15, 2004;
103(4):
1342 - 1347.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Minami, A. Sugiyama, S.-Q. Wu, R. Abid, T. Kodama, and W. C. Aird
Thrombin and Phenotypic Modulation of the Endothelium
Arterioscler Thromb Vasc Biol,
January 1, 2004;
24(1):
41 - 53.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. H. Sturn, N. C. Kaneider, C. Feistritzer, A. Djanani, K. Fukudome, and C. J. Wiedermann
Expression and function of the endothelial protein C receptor in human neutrophils
Blood,
August 15, 2003;
102(4):
1499 - 1505.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
D. J. Stearns-Kurosawa, K. Swindle, A. D'Angelo, P. Della Valle, A. Fattorini, N. Caron, M. Grimaux, B. Woodhams, and S. Kurosawa
Plasma levels of endothelial protein C receptor respond to anticoagulant treatment
Blood,
January 15, 2002;
99(2):
526 - 530.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kurosawa, C. T. Esmon, and D. J. Stearns-Kurosawa
The Soluble Endothelial Protein C Receptor Binds to Activated Neutrophils: Involvement of Proteinase-3 and CD11b/CD18
J. Immunol.,
October 15, 2000;
165(8):
4697 - 4703.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
