IngentaConnect Endothelium as a target for antiphospholipid antibodies

Authors: Riboldi P.¹; Gerosa M.¹; Raschi E.¹; Testoni C.¹; Meroni P.L.¹

Source: Immunobiology, Volume 207, Number 1, February 2003 , pp. 29-36(8)

Abstract:

Several, and not necessarily alternative, pathogenic mechanisms have been suggested to sustain the thrombophilic diathesis of the anti-phospholipid syndrome. Among them, interference of anti-phospholipid antibodies with cell acting in the coagulation cascade likely plays a major role. Anti-phospholipid antibodies have been shown to react with endothelial cells mainly by reacting with beta 2 glycoprotein I expressed on the cell membrane surface. Beta 2 glycoprotein I can adhere to endothelial cell surface through the Annexin II receptor and through negatively charged structures (heparin-like molecules) that are bound by the phospholipid-binding site of the molecule. The autoantibody binding involves a yet unknown receptor that activates a signalling pathway able to translocate NF kappav B from the cytoplasm to the nucleus and to activate genes for adhesion molecule, pro-inflammatory cytokine and Tissue Factor up-regulation. The ultimate effect is the induction of a pro-inflammatory and a pro-coagulant endothelial phenotype that has been reproduced both in vitro and in vivo experimental models. Additional effects of anti-phospholipid-mediated endothelial cell activation are the interference with the protein C/S system, with the Annexin V binding, the up-regulation of endothelin I synthesis and the induction of apoptosis. Altogether these effects cooperate in switching endothelium from an anti-coagulant to a pro-coagulant surface.

Language: English

Document Type: Original article

DOI: 10.1078/0171-2985-00211

Affiliations: 1: Allergy and Clinical Immunology Unit, IRCCS Istituto Auxologico Italiano, Department of Internal Medicine – University of Milan, Milan, Italy

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