HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gharavi, A. E. Articles by Harris, E. N. Search for Related Content PubMed PubMed Citation Articles by Gharavi, A. E. Articles by Harris, E. N.

GDKV-Induced Antiphospholipid Antibodies Enhance Thrombosis and Activate Endothelial Cells In Vivo and In Vitro¹

Azzudin E. Gharavi^2,*, Silvia S. Pierangeli, Margaret Colden-Stanfield, Xiao Wei Liu, Ricardo G. Espinola^§ and E. Nigel Harris^*

Departments of ^* Medicine, Microbiology and Immunology, Physiology, and ^§ Microbiology, Morehouse School of Medicine, Atlanta, GA 30310

Antiphospholipid (aPL) Abs are associated with thrombosis, pregnancy loss, and thrombocytopenia in patients with systemic lupus erythematosus or primary antiphospholipid syndrome (APS). ß₂-Glycoprotein I (ß₂GPI), a phospholipid-binding serum protein, is involved in aPL binding to phospholipids. aPL can be generated in mice by immunization with ß₂GPI, and these Abs are thrombogenic and cause pregnancy loss in mice. The objective of this study is to determine whether aPL induced by immunization with the phospholipid-binding site of ß₂GPI are thrombogenic and whether they activate endothelial cells (EC) in vivo and in vitro. Murine monoclonal aPL were generated from spleen cells of a mouse immunized with GDKV, a synthetic 15-aa peptide spanning Gly²⁷⁴–Cys²⁸⁸ in the fifth domain of human ß₂GPI, which represents the phospholipid-binding site of ß₂GPI. The Abs generated had aPL and anti-ß₂GPI activities. The effect of these Abs on thrombus formation and on EC activation in vivo was determined using a mouse model of thrombosis and microcirculation that enables examination of the adhesion of leukocyte to EC as an indication of EC activation as well as adhesion molecule expression using in vitro ELISA analysis. Mice injected with this monoclonal aPL showed a significant increase in leukocyte sticking and also produced larger thrombi that persisted longer. Exposure to GDKV-induced aPL for 4 h significantly increased surface Ag expression of E-selectin, ICAM-1, and VCAM-1. These data indicate that aPL induced by immunization with the phospholipid binding site of ß₂GPI are thrombogenic and activate endothelial cells.

This article has been cited by other articles:

				R. A Asherson, S. S Pierangeli, and R. Cervera Is there a microangiopathic antiphospholipid syndrome? Ann Rheum Dis, April 1, 2007; 66(4): 429 - 432. [Full Text] [PDF]

				M. Blank, I. Krause, L. Magrini, G. Spina, J. Kalil, S. Jacobsen, H. J. Thiesen, M. W. Cunningham, L. Guilherme, and Y. Shoenfeld Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome Rheumatology, July 1, 2006; 45(7): 833 - 841. [Abstract] [Full Text] [PDF]

				Y Shoenfeld, M Blank, R Cervera, J Font, E Raschi, and P-L Meroni Infectious origin of the antiphospholipid syndrome Ann Rheum Dis, January 1, 2006; 65(1): 2 - 6. [Full Text] [PDF]

				M. A. Ozturk, I. C. Haznedaroglu, M. Turgut, and H. Goker Current Debates in Antiphospholipid Syndrome: The Acquired Antibody-Mediated Thrombophilia Clinical and Applied Thrombosis/Hemostasis, April 1, 2004; 10(2): 89 - 126. [Abstract] [PDF]

				A E Gharavi, M Vega-Ostertag, R G Espinola, X Liu, L Cole, N T Cox, P Romagnoli, K Labat, and S S Pierangeli Intrauterine fetal death in mice caused by cytomegalovirus-derived peptide induced aPL antibodies Lupus, January 1, 2004; 13(1): 17 - 23. [Abstract] [PDF]

				A E Gharavi, W Wilson, and S Pierangeli The molecular basis of antiphospholipid syndrome Lupus, August 1, 2003; 12(8): 579 - 583. [Abstract] [PDF]

				S S Pierangeli and E N Harris Probing antiphospholipid-mediated thrombosis: the interplay between anticardiolipin antibodies and endothelial cells Lupus, July 1, 2003; 12(7): 539 - 545. [Abstract] [PDF]

				R Shamir, Y Shoenfeld, M Blank, R Eliakim, N Lahat, E Sobel, E Shinar, and A Lerner The prevalence of coeliac disease antibodies in patients with the antiphospholipid syndrome Lupus, May 1, 2003; 12(5): 394 - 399. [Abstract] [PDF]

				T. Arai, K. Yoshida, J. Kaburaki, H. Inoko, Y. Ikeda, Y. Kawakami, and M. Kuwana Autoreactive CD4+ T-cell clones to {beta}2-glycoprotein I in patients with antiphospholipid syndrome: preferential recognition of the major phospholipid-binding site Blood, September 15, 2001; 98(6): 1889 - 1896. [Abstract] [Full Text] [PDF]

				S. S. Pierangeli, R. G. Espinola, X. Liu, and E. N. Harris Thrombogenic Effects of Antiphospholipid Antibodies Are Mediated by Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and P-Selectin Circ. Res., February 2, 2001; 88(2): 245 - 250. [Abstract] [Full Text] [PDF]