ABSTRACT
Antiphospholipid antibodies (aPLs) are associated with an increased incidence of thrombosis, but the mechanisms responsible for thrombosis are unclear. The present study investigated the effect of both β2-glycoprotein I (β2-GPI) and aPLs on the activity of extrinsic fibrinolysis. The remaining tissue-plasminogen activator (t-PA) of the sample consisting of β2-GPI, two-chain recombinant t-PA, plasminogen activator inhibitor (PAI) -1 was measured by a chromogenic assay using synthetic substrate S-2251, Glu-plasminogen, and soluble fibrin monomer. Without PAI-1, β2-GPI did not affect t-PA activity. When 14.3 ng/ml PAI-1 was added to 3.6 U/ml t-PA, the remaining t-PA activity was increased from 48.9% to 60.4% by the addition of β2-GPI (190 μg/ml). The effect of β2-GPI did not require phospholipids. The β2-GPI seems to protect t-PA activity from the inhibition by PAI-1. When monoclonal anticardiolipin antibodies (aCLs), EY1C8, and EY2C9, which were established from a patient with antiphospholipid syndrome, were further added to the mixture with a diluted phospholipid (Platelin®) to investigate the influence of aPL, the remaining t-PA activity decreased to 50.1 and 80.7%. Monoclonal aCLs appeared to inhibit the effect of β2-GPI, that is, these monoclonals inhibited the fibrinolytic activity by an elevation in PAI-1 activity. These results suggest the possibility that the impairment of fibrinolytic activity by aCLs is one of reasons for the increased incidence in thrombosis in patients with aCLs.
KEYWORD
β2-Glycoprotein I - tissue-plasminogen activator (t-PA) - plasminogen activator inhibitor-1 (PAI-1) - monoclonal anticardiolipin antibody - chromogenic assay
