Annexin A2: biology and relevance to the antiphospholipid syndrome.
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.
Cockrell
E
E
Division of Pediatric, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Espinola
R G
RG
McCrae
K R
KR
D017306:Annexin A2 / Q000502:physiology*; D017152:Antibodies, Antiphospholipid / Q000502:physiology; D016736:Antiphospholipid Syndrome / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D001666:Binding Sites, Antibody; D042783:Endothelial Cells / Q000502:physiology*; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D010743:Phospholipids / Q000502:physiology; D013927:Thrombosis / Q000209:etiology*; D053482:beta 2-Glycoprotein I / Q000502:physiology
D017306:Annexin A2; D017152:Antibodies, Antiphospholipid; D010743:Phospholipids; D053482:beta 2-Glycoprotein I