MODULATION OF ENDOTHELIAL-CELL FUNCTION BY ANTIPHOSPHOLIPID ANTIBODIES

beta(2)-glycoprotein I (beta(2)-GP-I) the plasma cofactor for anti-pho spholipid antibodies adheres on the endothelial surfaces and can be re cognized by anti-beta(2)-GP-I antibodies naturally occurring in patien ts with the anti-phospholipid syndrome. As for the cofactor binding to cardiolipin- or gamma irradiated-plates, the endothelial binding is m ediated by the so-called phospholipid binding site, a cationic structu re able to react with anionic molecules. Endothelial monolayers appear to represent a substrate able to bind beta(2)-GP-I and to present it in a suitable manner in order to allow the binding of anti-beta(2)-GP- I beta(2) antibodies. The complex between beta(2)-GP-I and the respect ive antibodies induce an endothelial cell activation as demonstrated b y the up-regulation of adhesion molecule expression, the secretion of proinflammatory cytokines and the modulation of arachidonic acid metab olism. Taken together these findings strongly sustain a pivotal role f or beta(2)-GP-I in allowing antibody deposition on the endothelium and in affecting endothelial cell functions potentially responsible for a procoagulant state.