Thrombus formation induced by antibodies to beta2-glycoprotein I is complement dependent and requires a priming factor.
We monitored the number of intravascular platelet-leukocyte aggregates (PLAs) and thrombotic occlusions (TOs) by intravascular microscopy in the mesentery of rats receiving antiphospholipid (aPL) immunoglobulin G (IgG) purified from the sera of patients with antiphospholipid syndrome. aPL IgG had no procoagulant effect, but it caused rapid endothelial deposition of fibrinogen, followed by PLA and TO in rats receiving an intraperitoneal injection of bacterial lipopolysaccharide 3 hours before IgG infusion. Anti-beta2-glycoprotein I-depleted aPL IgG failed to induce PLAs and TOs. C3 and C9 colocalized with aPL IgG on the mesenteric vessels. The number of PLAs and TOs was markedly reduced in C6-deficient rats and in animals treated with anti-C5 miniantibody, suggesting the contribution of the terminal complement (C) complex to the aPL antibody-mediated intravascular thrombosis. In conclusion, our data indicate that antibodies to beta2-glycoprotein I trigger coagulation subsequent to a priming proinflammatory factor and that the terminal C complex is the main mediator of the coagulation process.
Fischetti
Fabio
F
Department of Physiology and Pathology, University of Trieste, Trieste, Italy.
Durigutto
Paolo
P
Pellis
Valentina
V
Debeus
Alessandra
A
Macor
Paolo
P
Bulla
Roberta
R
Bossi
Fleur
F
Ziller
Federica
F
Sblattero
Daniele
D
Meroni
Pierluigi
P
Tedesco
Francesco
F
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000737:chemistry; D001777:Blood Coagulation; D003176:Complement C3 / Q000378:metabolism; D003182:Complement C5 / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D003165:Complement System Proteins; D004730:Endothelium, Vascular / Q000166:cytology; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007249:Inflammation; D008070:Lipopolysaccharides; D008297:Male; D008856:Microscopy, Fluorescence; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D020246:Venous Thrombosis / Q000097:blood; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D003176:Complement C3; D003182:Complement C5; D003186:Complement C9; D006023:Glycoproteins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D053482:beta 2-Glycoprotein I; D005340:Fibrinogen; D003165:Complement System Proteins