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.

Automated summary

This study found that ss2GPI deficient mice have enhanced thrombus formation compared to wild type mice, and the antithrombotic function of ss2GPI is mainly dependent on its fifth domain.