Modulation of endothelial cell function by antiphospholipid antibodies.
beta 2-glycoprotein I (beta 2-GP-I) the plasma cofactor for anti-phospholipid antibodies adheres on the endothelial surfaces and can be recognized by anti-beta 2-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 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 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 beta 2-GP-I in allowing antibody deposition on the endothelium and in affecting endothelial cell functions potentially responsible for a procoagulant state.
Meroni
P L
PL
Istituto de Medicina Interna, Malattie Infettive Immunopatologia, IRCCS Policlinico, Milan, Italy.
Del Papa
N
N
Beltrami
B
B
Tincani
A
A
Balestrieri
G
G
Krilis
S A
SA
D017152:Antibodies, Antiphospholipid / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D013927:Thrombosis / Q000209:etiology; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I