Beta-2-glycoprotein I exerts antithrombotic function through its domain V in mice

Little is known about the physiological role of beta-2-glycoprotein I (ss2GPI) despite it being the major auto-antigen in the antiphospholipid syndrome. A systematic study of the role of ss2GPI in thrombus formation in vivo has not been performed to date. Herein, we report that ss2GPI deficient (-/-) mice have enhanced thrombus formation compared to wild type (WT) mice in a laser-induced arteriole and venule model of thrombosis. Furthermore, neutrophil accumulation and elastase activity was enhanced in thrombi of ss2GPI -/-compared with WT mice. The antithrombotic function of ss2GPI is dependent on its fifth domain (domain V); intravenous administration of the ss2GPI domain deletion mutant lacking domain V (human recombinant domain I-IV) had no effect on platelet and fibrin thrombus size in ss2GPI -/-or WT mice. On the contrary, intravenous adminis-tration of human recombinant domain V significantly inhibited platelet and fibrin thrombus size in both ss2GPI -/-mice and WT mice. These findings reveal a major role for ss2GPI as a natural anticoagulant and implicate domain V of ss2GPI as a potential antithrombotic therapy.