The role of beta2-glycoprotein I (beta2GPI) in the activation of plasminogen.
Beta2-glycoprotein I (beta2GPI) is a glycoprotein of unknown physiological function. It is the main target antigen for antiphospholipid antibodies in patients with antiphospholipid syndrome (APS). beta2GPI 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 beta2GPI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta2GPI. 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 beta2GPI added, suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA. This phenomenon represents a novel regulatory step both in the positive feedback mechanism for extrinsic fibrinolysis and in antithrombotic regulation. IgG anti-beta2GPI antibodies recognized the beta2GPI at the endothelial surface inducing its activation with an increase of ICAM-I 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-beta2GPI antibodies could generate thrombosis as observed in APS.
López-Lira
Francisco
F
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, UNAM, Ciudad Universitaria 04510, México, D.F., Mexico.
Rosales-León
Luis
L
Martínez
Verónica Monroy
VM
Ruiz Ordaz
Blanca H
BH
D000906:Antibodies; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D004789:Enzyme Activation; D005342:Fibrinolysis; D006023:Glycoproteins / Q000276:immunology / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D018082:Kringles / Q000502:physiology; D010958:Plasminogen / Q000378:metabolism*; D018180:Thrombomodulin / Q000096:biosynthesis; D053482:beta 2-Glycoprotein I
D000906:Antibodies; D006023:Glycoproteins; D018180:Thrombomodulin; D053482:beta 2-Glycoprotein I; D018799:Intercellular Adhesion Molecule-1; D010958:Plasminogen