Thrombus formation induced by antibodies to β2-glycoprotein I is complement dependent and requires a priming factor

被引:261
作者
Fischetti, F
Durigutto, P
Pellis, V
Debeus, A
Macor, P
Bulla, R
Bossi, F
Ziller, F
Sblattero, D
Meroni, P
Tedesco, F
机构
[1] Univ Trieste, Dept Physiol & Pathol, I-34127 Trieste, Italy
[2] Univ Trieste, Dept Med & Neurol, I-34127 Trieste, Italy
[3] Univ Eastern Piedmont, Dept Med Sci, Vercelli, Italy
[4] Univ Milan, IRCCS Ist Auxol Italiano, Dept Internal Med, Allergy & Clin Immunol Sect, Milan, Italy
关键词
D O I
10.1182/blood-2005-03-1319
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We monitored the number of intravascular platelet-leukocyte aggregates (PLAs) and thrombotic occlusions (TOs) by intravascular microscopy in the mesentery of rats receiving anti phospholipid (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-beta 2-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 beta 2-glycoprotein I trigger coagulation subsequent to a priming proinflammatory factor and that the terminal C complex is the main mediator of the coagulation process.
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收藏
页码:2340 / 2346
页数:7
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