Annexin A2: biology and relevance to the antiphospholipid syndrome.

Abstract

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 discussed.

• Authors: E Cockrell, R G Espinola, K R McCrae
• Journal: Lupus (Lupus) Vol. 17 Issue 10 Pg. 943-51 (Oct 2008) ISSN: 0961-2033 [Print] England
• PMID: 18827060 (Publication Type: Journal Article, Review)

Chemical References

• Annexin A2
• Antibodies, Antiphospholipid
• Phospholipids
• beta 2-Glycoprotein I

Topics

• Annexin A2 (physiology)
• Antibodies, Antiphospholipid (physiology)
• Antiphospholipid Syndrome (complications, pathology, physiopathology)
• Binding Sites, Antibody
• Endothelial Cells (physiology)
• Fibrinolysis (physiology)
• Humans
• Phospholipids (physiology)
• Thrombosis (etiology)
• beta 2-Glycoprotein I (physiology)