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.

journal_name

Lupus

journal_title

Lupus

authors

Cockrell E,Espinola RG,McCrae KR

doi

10.1177/0961203308095329

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

943-51

issue

10

eissn

0961-2033

issn

1477-0962

pii

17/10/944

journal_volume

17

pub_type

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