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Blood, 1 March 2005, Vol. 105, No. 5, pp. 1964-1969. Prepublished online as a Blood First Edition Paper on October 7, 2004; DOI 10.1182/blood-2004-05-1708. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-05-1708v1 105/5/1964    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Articles by McCrae, K. R. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by McCrae, K. R. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Annexin A2 mediates endothelial cell activation by antiphospholipid/anti-2 glycoprotein I antibodies Jianwei Zhang, and Keith R. McCrae From the Department of Medicine, Hematology-Oncology Division, Case Western Reserve University School of Medicine, Cleveland, OH. Patients with antiphospholipid antibodies (APLAs) are at increased risk for arterial and venous thrombosis. Many APLAs associated with these events react with 2 glycoprotein I (2GPI), and endothelial cell reactive antibodies that activate endothelial cells in a 2GPI-dependent manner occur commonly in these patients. We previously reported that 2GPI binds with high affinity to annexin A2 on the endothelial surface, though the relevance of this interaction to APLA/anti-2GPI antibody–induced endothelial activation has not been determined. In this report, we confirm that anti-2GPI antibodies activate endothelial cells in the presence of 2GPI, and demonstrate that anti–annexin A2 antibodies directly cause endothelial cell activation of a similar magnitude and with a similar time course. Moreover, bivalent anti–annexin A2 F(ab')2 fragments also caused endothelial cell activation, whereas monomeric Fab fragments not only did not cause activation, but blocked activation induced by anti–annexin A2 antibodies and F(ab')2 fragments, as well as that caused by anti-2GPI antibodies in the presence of 2GPI. These observations suggest a novel pathway for endothelial activation induced by APLA/anti-2GPI antibodies that is initiated by cross-linking or clustering of annexin A2 on the endothelial surface. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Annexin A2: better left alone Alisa S. Wolberg and Robert A. S. Roubey Blood 2005 105: 1845-1846. [Full Text] [PDF] This article has been cited by other articles: Z. Romay-Penabad, M. G. Montiel-Manzano, T. Shilagard, E. Papalardo, G. Vargas, A. B. Deora, M. Wang, A. T. Jacovina, E. Garcia-Latorre, E. Reyes-Maldonado, et al. Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo Blood, October 1, 2009; 114(14): 3074 - 3083. [Abstract] [Full Text] [PDF] E Raschi, M. Borghi, C Grossi, V Broggini, S Pierangeli, and P. Meroni Toll-like receptors: another player in the pathogenesis of the anti-phospholipid syndrome Lupus, October 1, 2008; 17(10): 938 - 943. [Abstract] [PDF] E Cockrell, R. Espinola, and K. McCrae Annexin A2: biology and relevance to the antiphospholipid syndrome Lupus, October 1, 2008; 17(10): 944 - 952. 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Kruithof, and P. de Moerloose The role of TLR2 in the inflammatory activation of mouse fibroblasts by human antiphospholipid antibodies Blood, February 15, 2007; 109(4): 1507 - 1514. [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] 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] M V. Ostertag, X Liu, V Henderson, and S S Pierangeli A peptide that mimics the Vth region of {beta}2glycoprotein I reverses antiphospholipid-mediated thrombosis in mice Lupus, June 1, 2006; 15(6): 358 - 365. [Abstract] [PDF] K. R. 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