ROLE OF BETA(2)-GLYCOPROTEIN-I AND ANTIPHOSPHOLIPID ANTIBODIES IN ACTIVATION OF PROTEIN-C IN-VITRO

Aims-To investigate the effect of beta2-glycoprotein I (beta2 GPI) on the thrombin/thrombomodulin dependent activation of protein C; and to determine whether beta2 GPI dependent anticardiolipin antibodies have any effect. Methods-Protein C was activated by thrombin in the presenc e of thrombomodulin and phospholipid vesicles in an in vitro system. T he effect of adding purified beta2 GPI to this system was observed. Af finity purified anticardiolipin antibodies and total IgG from patients with anticardiolipin antibodies and the lupus anticoagulant were stud ied for their effects on protein C activation in the presence and abse nce of beta2 GPI. Results-beta2-Glycoprotein I had no effect on the ac tivity of preformed activated protein C. When the phospholipid vesicle s were incubated with beta2 GPI before the addition of protein C, the activation of protein C was inhibited in a dose dependent manner. With phosphatidylserine:phosphatidylcholine vesicles at a concentration of 1 muM:2 muM, beta2 GPI began to inhibit the reaction at a concentrati on of 15 nM, and at 4 muM (the normal plasma concentration) the activa tion of protein C was reduced to 40%. Anticardiolipin antibodies had n o demonstrable effect. Conclusions-beta2-Glycoprotein I inhibits prote in C activation in an in vitro system. Its physiological role is unkno wn but it has potential procoagulant as well as anticoagulant properti es. An effect of antiphospholipid antibodies on protein C activation, which might explain their association with thrombosis, could not be sh own.