Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo
| Autor: | Tuya Shilagard, Ethel García-Latorre, Arun B. Deora, Maria Guadalupe Montiel-Manzano, Silvia S. Pierangeli, Andrew T. Jacovina, Katherine A. Hajjar, Michael Wang, Gracie Vargas, Elba Reyes-Maldonado, Elizabeth Papalardo, Zurina Romay-Penabad |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Umbilical Veins medicine.drug_class Blotting Western Immunology Vascular Cell Adhesion Molecule-1 Enzyme-Linked Immunosorbent Assay In Vitro Techniques Monoclonal antibody Biochemistry Immunoglobulin G Thromboplastin Thrombosis and Hemostasis Mice Tissue factor In vivo Annexin medicine Animals Humans Annexin A2 Aorta Cells Cultured Mice Knockout biology Cell Biology Hematology Middle Aged Antiphospholipid Syndrome Intercellular Adhesion Molecule-1 Molecular biology Mice Inbred C57BL Carotid Arteries Cardiovascular Diseases Monoclonal Antibodies Antiphospholipid biology.protein Endothelium Vascular Antibody E-Selectin |
| Zdroj: | Blood. 114:3074-3083 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2008-11-188698 |
| Popis: | Antiphospholipid (aPL) antibodies recognize receptor-bound beta(2) glycoprotein I (beta(2)GPI) 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 beta(2)GPI 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-beta(2)GPI 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. |
| Databáze: | OpenAIRE |
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