The role of β2-glycoprotein I (β2GPI) in the activation of plasminogen

beta 2-glycoprotein I (beta(2)GPI) is a glycoprotein of unknown physiological function. It is the main target antigen for antiphospholipid antibodies in patients with antiphospholipid syndrome (APS). beta(2)GPI binds with high affinity to the atherogenic lipoprotein Lp(a) which shares structural homology with plasminogen, a key molecule in the fibrinolytic system. Impaired fibrinolysis has been described in APS. The present work reports the interaction between beta(2)GpI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta(2)GPI. In the process of Glu-Plasminogen activation, we found an increase in plasmin generation both at fibrin and cellular surface level as a function of the concentration of beta(2)GPI added, suggesting an important role as a cofactor in the trimolecular complex beta(2)GPI-Plasminogen-tPA. This phenomenon represents a novel regulatory step both in the positive feedback mechanism for extrinsic fibrinolysis and in antithrombotic regulation. IgG anti-beta(2)-GPI antibodies recognized the beta(2)GPI at the endothelial surface inducing its activation with an increase of ICAM-1 and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium. The interference in the plasmin conversion by anti-beta(2)GPI antibodies could generate thrombosis as observed in APS. (c) 2005 Elsevier B.V. All rights reserved.