|
|
Blood, 1 December 2004, Vol. 104, No. 12, pp. 3624-3630.
Prepublished online as a Blood First Edition Paper on August 3, 2004; DOI 10.1182/blood-2004-03-1146.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Inhibition of thrombin generation by protein S at low procoagulant stimuli: implications for maintenance of the hemostatic balance
Kristin M. Seré,
Jan Rosing, and
Tilman M. Hackeng
From the Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, the Netherlands.
The activated protein C (APC)–independent anticoagulant activity of protein S on tissue factor–induced thrombin generation was quantified in plasma. In absence of APC, protein S significantly decreased the endogenous thrombin potential (ETP) in a concentration-dependent manner. The APC-independent anticoagulant activity of protein S in plasma was not affected by phospholipid concentrations but strongly depended on tissue factor concentrations: protein S inhibited the ETP from 6% at 140 pM tissue factor to 74% at 1.4 pM tissue factor. Plasma with both 60% protein S and 140% prothrombin showed an ETP of 240% compared to normal plasma, suggesting an APC-independent protective role of protein S in the development of thrombosis as a result of protein S deficiency and the prothrombin-G20210A mutation. At high tissue-factor concentrations, protein S hardly expressed APC-independent anticoagulant activity but exerted potent APC-cofactor activity when thrombomodulin or APC were added to plasma. Neutralization of protein S under these conditions resulted in a 20-fold reduction of the anticoagulant activity of APC. The present study shows that protein S effectively regulates coagulation at 2 levels: at low procoagulant stimuli, protein S maintains the hemostatic balance by directly inhibiting thrombin formation, and at high procoagulant stimuli, protein S restores the hemostatic balance via its APC-cofactor activity.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Letter in Blood Online:
-
Analyses of protein S function
- Kenneth G. Mann, Tilman M. Hackeng, Kristin M. Seré, and Jan Rosing
Blood 2005 106: 1884-1885.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
T. M. Hackeng and J. Rosing
Protein S as Cofactor for TFPI
Arterioscler Thromb Vasc Biol,
December 1, 2009;
29(12):
2015 - 2020.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. S. Preston, S. Tran, J. A. Johnson, F. N. Ainle, S. Harmon, B. White, O. P. Smith, P. V. Jenkins, B. Dahlback, and J. S. O'Donnell
Platelet Factor 4 Impairs the Anticoagulant Activity of Activated Protein C
J. Biol. Chem.,
February 27, 2009;
284(9):
5869 - 5875.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. F. A. Maurissen, M. C. L. G. D. Thomassen, G. A. F. Nicolaes, B. Dahlback, G. Tans, J. Rosing, and T. M. Hackeng
Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation
Blood,
March 15, 2008;
111(6):
3034 - 3041.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. S. Preston, E. Ajzner, C. Razzari, S. Karageorgi, S. Dua, B. Dahlback, and D. A. Lane
Multifunctional Specificity of the Protein C/Activated Protein C Gla Domain
J. Biol. Chem.,
September 29, 2006;
281(39):
28850 - 28857.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. M. Hackeng, K. M. Sere, G. Tans, and J. Rosing
Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor
PNAS,
February 28, 2006;
103(9):
3106 - 3111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. G. Mann, T. M. Hackeng, K. M. Sere, and J. Rosing
Analyses of protein S function
Blood,
September 1, 2005;
106(5):
1884 - 1885.
[Full Text]
[PDF]
|
|
|
|
|
