Journal
LUPUS
Volume 17, Issue 10, Pages 943-951Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0961203308095329
Keywords
annexin; antiphospholipid; beta(2)-glycoprotein I; enothelial; thrombosis
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Funding
- NHLBI NIH HHS [P50 HL081011] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P50HL081011] Funding Source: NIH RePORTER
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Antiphospholipid antibodies (aPL), the majority of which are directed against beta(2)-glycoprotein I (beta(2)GPI), are associated with an increased incidence of venous and arterial thrombosis. The pathogenesis of antiphospholipid/anti-beta(2)GPI-associated thrombosis has not been defined, and is likely multifactorial. However, accumulating evidence suggests an important role for endothelial cell activation with the acquisition of a procoagulant phenotype by the activated endothelial cell. Previous work demonstrated that endothelial activation by antiphospholipid/anti-beta(2)GPI antibodies is beta(2)GPI-dependent. We extended these observations by defining annexin A2 as an endothelial beta(2)GPI binding site. We also observed that annexin A2 plays a critical role in endothelial cell activation induced by anti-beta(2)GPI antibodies, and others have described direct endothelial activation by anti-annexin A2 antibodies in patients with aPL. Similar findings have been reported using human monocytes, which also express annexin A2. Because annexin A2 is not a transmembrane protein, how binding of beta(2)GPI/anti-beta(2)GPI antibodies, or anti-annexin A2 antibodies, to endothelial annexin A2 causes cellular activation is unknown. Recent studies, however, suggest an important role for the Toll-like receptor family, particularly TLR4. In this article, we review the role of these interactions in the activation of endothelial cells by aPL. The influence of these antibodies on the ability of annexin A2 to enhance t-PA-mediated plasminogen activation is also discusses. Lupus (2008) 17, 943-951.
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