Modulation of Endothelial Cell Function by Antiphospholipid Antibodies

Abstract

β₂-glycoprotein I (β₂-GP-I) the plasma cofactor for anti-phospholipid antibodies adheres on the endothelial surfaces and can be recognized by anti-β₂-GP-I antibodies naturally occurring in patients with the anti-phospholipid syndrome. As for the cofactor binding to cardiolipin- or gamma irradiated-plates, the endothelial binding is mediated by the so-called phospholipid binding site, a cationic structure able to react with anionic molecules. Endothelial monolayers appear to represent a substrate able to bind β₂-GP-I and to present it in a suitable manner in order to allow the binding of anti-β₂-GP-I β2 antibodies. The complex between β₂-GP-I and the respective antibodies induce an endothelial cell activation as demonstrated by the up-regulation of adhesion molecule expression, the secretion of proinflammatory cytokines and the modulation of arachidonic acid metabolism. Taken together these findings strongly sustain a pivotal role for β₂-GP-I in allowing antibody deposition on the endothelium and in affecting endothelial cell functions potentially responsible for a procoagulant state.