Effects of beta2-glycoprotein I and monoclonal anticardiolipin antibodies on extrinsic fibrinolysis.
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 beta2-glycoprotein I (beta2-GPI) and aPLs on the activity of extrinsic fibrinolysis. The remaining tissue-plasminogen activator (t-PA) of the sample consisting of beta2-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, beta2-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 beta2-GPI (190 microg/ml). The effect of beta2-GPI did not require phospholipids. The beta2-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 beta2-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.
Ieko
M
M
Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan. iekom@hoku-iryo-u.ac.jp
Ichikawa
K
K
Atsumi
T
T
Takeuchi
R
R
Sawada
K I
KI
Yasukouchi
T
T
Koike
T
T
D017153:Antibodies, Anticardiolipin / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D016736:Antiphospholipid Syndrome / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D002863:Chromogenic Compounds / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D019851:Thrombophilia / Q000503:physiopathology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D002863:Chromogenic Compounds; D006023:Glycoproteins; D009842:Oligopeptides; D010743:Phospholipids; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; D053482:beta 2-Glycoprotein I; C018788:valyl-leucyl-lysine 4-nitroanilide; D010959:Tissue Plasminogen Activator