Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo

Zurina Romay-Penabad, Maria Guadalupe Montiel-Manzano, Tuya Shilagard, Elizabeth Papalardo, Gracie Vargas, Arun B. Deora, Michael Wang, Andrew T. Jacovina, Ethel Garcia-Latorre, Elba Reyes-Maldonado, Katherine A. Hajjar, Silvia S. Pierangeli

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

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 immunoglobulinG(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.

Original languageEnglish (US)
Pages (from-to)3074-3083
Number of pages10
JournalBlood
Volume114
Issue number14
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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