|
|
Blood, 1 September 2005, Vol. 106, No. 5, pp. 1629-1635.
Prepublished online as a Blood First Edition Paper on May 12, 2005; DOI 10.1182/blood-2005-01-0404.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Inhibition of APC anticoagulant activity on oxidized phospholipid by anti– 2-glycoprotein I monoclonal antibodies
Omid Safa,
Charles T. Esmon, and
Naomi L. Esmon
From the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City; Department of Pathology and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City; and Howard Hughes Medical Institute, Oklahoma City, OK.
Activated protein C (APC) anticoagulant activity and the ability to be inhibited by auto-antibodies associated with thrombosis are strongly augmented by the presence of phosphatidylethanolamine (PE) and phospholipid oxidation.  2-glycoprotein I (2-GPI) is a major antigen for antiphospholipid antibodies present in patients with the antiphospholipid syndrome. We therefore investigated whether anti–2-GPI monoclonal antibodies (mAbs) could inhibit APC with similar membrane specificity. Five mouse mAbs that reacted with different epitopes on 2-GPI were examined. Each inhibited the PE-, phospholipid oxidation–dependent enhancement of APC anticoagulant activity and required antibody divalency. A chimeric APC that retains anticoagulant activity but is relatively unaffected by protein S, PE, or oxidation was not inhibited by the antibodies. In purified systems, anti–2-GPI mAb inhibition of factor Va inactivation was greater in the presence of protein S and required 2-GPI. Surprisingly, although the mAbs did increase 2-GPI affinity for membranes, PE and oxidation had little influence on the affinity of the 2-GPI antibody complex for the membrane vesicles. We conclude that antibodies to 2-GPI inhibit APC function specifically and contribute to a hypercoaguable state by disrupting specific protein-protein interactions induced by oxidation of PE-containing membranes.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Giannakopoulos and S. A. Krilis
How I treat the antiphospholipid syndrome
Blood,
September 3, 2009;
114(10):
2020 - 2030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D'Angelo and S. Vigano D'Angelo
Protein S deficiency
Haematologica,
April 1, 2008;
93(4):
498 - 501.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Membre, D. Wahl, V. Latger-Cannard, J.-P. Max, P. Lacolley, T. Lecompte, and V. Regnault
The effect of platelet activation on the hypercoagulability induced by murine monoclonal antiphospholipid antibodies
Haematologica,
April 1, 2008;
93(4):
566 - 573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Giannakopoulos, F. Passam, S. Rahgozar, and S. A. Krilis
Current concepts on the pathogenesis of the antiphospholipid syndrome
Blood,
January 15, 2007;
109(2):
422 - 430.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
