title: Effects of beta2-glycoprotein I and monoclonal anticardiolipin antibodies on extrinsic fibrinolysis.
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 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.
authors.affiliation: Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan. iekom@hoku-iryo-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Ieko
authors.forename: K
authors.initials: K
authors.lastname: Ichikawa
authors.forename: T
authors.initials: T
authors.lastname: Atsumi
authors.forename: R
authors.initials: R
authors.lastname: Takeuchi
authors.forename: K I
authors.initials: KI
authors.lastname: Sawada
authors.forename: T
authors.initials: T
authors.lastname: Yasukouchi
authors.forename: T
authors.initials: T
authors.lastname: Koike
mesh_terms: 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
chemical_list: 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