ANTITHROMBIN-III STIMULATES PROSTAGLANDIN I-2 PRODUCTION BY CULTURED RAT HEPATIC SINUSOIDAL ENDOTHELIAL-CELLS

We examined the production of prostanoids, specifically prostaglandin (PG) I-2 and thromboxane (TX) A(2), 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(1 alpha) (a stable metabolite of PG I-2) increased significa ntly and in a dose-dependent manner, compared with production by untre ated 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 mu g/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 sig nificantly reduced with increasing concentrations of heparin. On the o ther hand, TX B-2 (a stable metabolite of TX A(2)) production was unaf fected by AT III treatment. These data suggest that AT III may amelior ate the liver damage or disturbances in the sinusoidal microcirculatio n by stimulating the PG I-2 production of hepatic sinusoidal endotheli al cells. (C) 1996 Elsevier Science Ireland Ltd.