beta 2-Glycoprotein I modulates the anticoagulant activity of activated protein C on the phospholipid surface.
The objective of this study was to determine whether beta 2-glycoprotein I (beta 2GPI) has procoagulant activity by inhibiting the anticoagulant activity of activated protein C (APC). beta 2GPI inhibited significantly the APC-catalyzed inactivation of factor Va in an assay using factor V-deficient plasma and physiological levels of protein S and factor Va. This inhibitory effect was diminished by the addition of increasing concentrations of phospholipids, suggesting that beta 2GPI competitively inhibits the binding of APC to the phospholipid surface. beta 2GPI inhibited weakly factor Va- and phospholipid-dependent prothrombinase activity at concentrations similar to those to inhibit APC activity. The depletion of beta 2GPI from plasma led to only a slight shortening of the diluted Russell's viper venom-dependent clotting time, but to a strong and significant potentiation of the anticoagulant activity of APC. These results suggest that under certain physiological conditions beta 2GPI has procoagulant property by inhibiting the phospholipid-dependent APC anticoagulant activity.
Mori
T
T
Department of Molecular Pathobiology, Mie University School of Medicine, Tsu-city, Japan.
Takeya
H
H
Nishioka
J
J
Gabazza
E C
EC
Suzuki
K
K
D000925:Anticoagulants / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002384:Catalysis; D005069:Evaluation Studies as Topic; D005165:Factor V / Q000378:metabolism; D005166:Factor V Deficiency / Q000097:blood; D015943:Factor Va / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D015951:Factor Xa; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D011486:Protein C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017293:Protein S / Q000378:metabolism; D011517:Prothrombin Time; D053482:beta 2-Glycoprotein I
D000925:Anticoagulants; D006023:Glycoproteins; D010743:Phospholipids; D011486:Protein C; D017293:Protein S; D053482:beta 2-Glycoprotein I; C022475:prothrombinase complex; D015943:Factor Va; D005165:Factor V; D005170:Factor X; D015951:Factor Xa