|
|
Blood, 15 May 2006, Vol. 107, No. 10, pp. 3912-3921.
Prepublished online as a Blood First Edition Paper on January 24, 2006; DOI 10.1182/blood-2005-08-3130.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Roles of protease-activated receptors in a mouse model of endotoxemia
Eric Camerer,
Ivo Cornelissen,
Hiroshi Kataoka,
Daniel N. Duong,
Yao-Wu Zheng, and
Shaun R. Coughlin
From the Cardiovascular Research Institute, University of California, San Francisco.
Endotoxemia is often associated with extreme inflammatory responses and disseminated intravascular coagulation. Protease-activated receptors (PARs) mediate cellular responses to coagulation proteases, including platelet activation and endothelial cell reactions predicted to promote inflammation. These observations suggested that PAR activation by coagulation proteases generated in the setting of endotoxemia might promote platelet activation, leukocyte-mediated endothelial injury, tissue damage, and death. Toward testing these hypotheses, we examined the effect of PAR deficiencies that ablate platelet and endothelial activation by coagulation proteases in a mouse endotoxemia model. Although coagulation was activated as measured by thrombin-antithrombin (TAT) production and antithrombin III (ATIII) depletion, Par1–/–, Par2–/–, Par4–/–, Par2–/–:Par4–/–, and Par1–/–:Par2–/– mice all failed to show improved survival or decreased cytokine responses after endotoxin challenge compared with wild type. Thus, our results fail to support a necessary role for PARs in linking coagulation to inflammation or death in this model. Interestingly, endotoxin-induced thrombocytopenia was not diminished in Par4–/– mice. Thus, a mechanism independent of platelet activation by thrombin was sufficient to cause thrombocytopenia in our model. These results raise the possibility that decreases in platelet count in the setting of sepsis may not be caused by disseminated intravascular coagulation but instead report on a sometimes parallel but independent process.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
V. Shpacovitch, M. Feld, M. D. Hollenberg, T. A. Luger, and M. Steinhoff
Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity
J. Leukoc. Biol.,
June 1, 2008;
83(6):
1309 - 1322.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Chauhan, M. T. Walsh, G. Zhu, D. Ginsburg, D. D. Wagner, and D. G. Motto
The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis
Blood,
April 1, 2008;
111(7):
3452 - 3457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Schuepbach, C. Feistritzer, L. F. Brass, and M. Riewald
Activated protein C-cleaved protease activated receptor-1 is retained on the endothelial cell surface even in the presence of thrombin
Blood,
March 1, 2008;
111(5):
2667 - 2673.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Weiler and W. Ruf
PAR4 antagonists in inflammation
Blood,
November 1, 2007;
110(9):
3091 - 3092.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Slofstra, M. F. Bijlsma, A. P. Groot, P. H. Reitsma, T. Lindhout, H. ten Cate, and C. A. Spek
Protease-activated receptor-4 inhibition protects from multiorgan failure in a murine model of systemic inflammation
Blood,
November 1, 2007;
110(9):
3176 - 3182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Moussa, J. Apostolopoulos, P. Davenport, J. Tchongue, and P. G. Tipping
Protease-Activated Receptor-2 Augments Experimental Crescentic Glomerulonephritis
Am. J. Pathol.,
September 1, 2007;
171(3):
800 - 808.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ahamed, F. Niessen, T. Kurokawa, Y. K. Lee, G. Bhattacharjee, J. H. Morrissey, and W. Ruf
Regulation of macrophage procoagulant responses by the tissue factor cytoplasmic domain in endotoxemia
Blood,
June 15, 2007;
109(12):
5251 - 5259.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Hirano
The Roles of Proteinase-Activated Receptors in the Vascular Physiology and Pathophysiology
Arterioscler. Thromb. Vasc. Biol.,
January 1, 2007;
27(1):
27 - 36.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Ware, E. Camerer, K. Welty-Wolf, M. J. Schultz, and M. A. Matthay
Bench to bedside: targeting coagulation and fibrinolysis in acute lung injury
Am J Physiol Lung Cell Mol Physiol,
September 1, 2006;
291(3):
L307 - L311.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
