Antithrombin III stimulates prostaglandin I2 production by cultured rat hepatic sinusoidal endothelial cells

Abstract

We examined the production of prostanoids, specifically prostaglandin (PG) I₂ and thromboxane (TX) A₂, in cultured rat hepatic sinusoidal endothelial cells treated with antithrombin (AT) III. When cells were treated for 3 h with various concentration of AT III, production of 6-keto-PGF_1α (a stable metabolite of PG I₂) increased significantly and in a dose-dependent manner, compared with production by untreated cells. In terms of kinetics, significant increases were noted at 3 h (20.13 ± 1.38 pg/ml), 4 h (21.23 ± 0.63 pg/ml) and 24 h (36.58 ± 4.93 pg/ml) with AT III (300 μg/ml) stimulation, compared with production by the untreated cells (10.29 ± 1.21, 10.34 ± 1.66 and 22.64 ± 2.59 pg/ml, respectively). Moreover, this production was significantly reduced with increasing concentrations of heparin. On the other hand, TX B₂ (a stable metabolite of TX A₂) production was unaffected by AT III treatment. These data suggest that AT III may ameliorate the liver damage or disturbances in the sinusoidal microcirculation by stimulating the PG I₂ production of hepatic sinusoidal endothelial cells.