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Blood, 1 October 2009, Vol. 114, No. 14, pp. 3074-3083. Prepublished online as a Blood First Edition Paper on July 23, 2009; DOI 10.1182/blood-2008-11-188698. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-11-188698v1 114/14/3074    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 CrossRef Google Scholar Articles by Romay-Penabad, Z. Articles by Pierangeli, S. S. PubMed PubMed Citation Articles by Romay-Penabad, Z. Articles by Pierangeli, S. S. Related Collections Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo Zurina Romay-Penabad1, Maria Guadalupe Montiel-Manzano2, Tuya Shilagard3, Elizabeth Papalardo1, Gracie Vargas3,4, Arun B. Deora5, Michael Wang1, Andrew T. Jacovina5, Ethel Garcia-Latorre6, Elba Reyes-Maldonado7, Katherine A. Hajjar5, and Silvia S. Pierangeli1 1 Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston; 2 Hematology Department, Specialty Hospital, National Medical Center, Instituto Mexicano de Segura Social (IMSS), Mexico City, Mexico; 3 Center for Biomedical Engineering, and 4 Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston; 5 Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY; and Departments of 6 Immunology and 7 Morphology, Instituto Politecnico Nacional, Mexico City, Mexico Antiphospholipid (aPL) antibodies recognize receptor-bound β2 glycoprotein I (β2GPI) on target cells, and induce an intracellular signaling and a procoagulant/proinflammatory phenotype that leads to thrombosis. Evidence indicates that annexin A2 (A2), a receptor for tissue plasminogen activator and plasminogen, binds β2GPI on target cells. However, whether A2 mediates pathogenic effects of aPL antibodies in vivo is unknown. In this work, we studied the effects of human aPL antibodies in A2-deficient (A2–/–) mice. A2–/– and A2+/+ mice were injected with immunoglobulin G (IgG) isolated from either a patient with antiphospholipid syndrome (IgG-APS), a healthy control subject (IgG-normal human serum), a monoclonal anti-β2GPI antibody (4C5), an anti-A2 monoclonal antibody, or monoclonal antibody of irrelevant specificity as control. We found that, after IgG-APS or 4C5 injections and vascular injury, mean thrombus size was significantly smaller and tissue factor activity was significantly less in A2–/– mice compared with A2+/+ mice. The expression of vascular cell adhesion molecule-1 induced by IgG-APS or 4C5 in explanted A2–/– aorta was also significantly reduced compared with A2+/+ mice. Interestingly, anti-A2 monoclonal antibody significantly decreased aPL-induced expression of intercellular cell adhesion molecule-1, E-selectin, and tissue factor activity on cultured endothelial cells. Together, these data indicate for the first time that A2 mediates the pathogenic effects of aPL antibodies in vivo and in vitro APS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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