title: Endothelium activation in the anti-phospholipid syndrome.
abstract: Anti-phospholipid syndrome is an autoimmune systemic disease characterized by the persistent presence of anti-phospholipid antibodies and by the occurrence of thrombosis, fetal loss and thrombocytopenia. Anti-phospholipid antibodies are widely accepted as pathogenic antibodies mainly directed against the phospholipid-binding protein beta 2 glycoprotein I. Beta 2 glycoprotein I can be expressed on the endothelial cell membranes of different anatomical localizations and recognized by the autoantibodies. The antibody binding might induce an endothelial activation both in vitro and in vivo experimental models, that was suggested to represent one of the pathogenic mechanisms leading to the prothrombotic state of the syndrome. Beta 2 glycoprotein I endothelial adhesion was found to take place through the interaction of the cationic phospholipid binding site of the molecule with anionic endothelial structures and through annexin II, the endothelial cell receptor for tissue plasminogen activator. Anti-beta 2 glycoprotein I antibodies can directly activate the cells via NF-kB translocation and the signaling cascade triggered by toll like receptors. It has been suggested that beta 2 glycoprotein I might be associated with toll like receptors because of its molecular mimicry with bacterial structures, the natural ligands of toll like receptors. The binding of the antibodies is thought to cross-link beta 2 glycoprotein I and the toll like receptors, eventually switching their signaling pathway.
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D015398:Signal Transduction; D053482:beta 2-Glycoprotein I
chemical_list: D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I