Antithrombin III prevents concanavalin A-induced liver injury through inhibition of macrophage inflammatory protein-2 release and production of prostacyclin in mice

Background/Aims: Recently, we have reported that macrophage inflammatory protein-2 (MIP-2) plays a pivotal role in concanavalin A (Con A)-induced liver injury. In this study, we investigated the effect of antithrombin III (AT-III) on liver damage, and production of MIP-2 and prostacyclin in this model. Methods: Liver injury was induced by intravenous injection of Con A (15 mg/kg) and AT-III was administered (50, 250 and 500 units/kg, iv) 30 mm before Con A injection. Plasma levels of alanine aminotransferase (ALT), MIP-2 and 6-keto-prostaglandin F1α (6k-PG-F1α), stable metabolite of prostaglandin I2 (prostacyclin), were determined. Results: The elevated plasma ALT levels 8, 16, 24 h after Con A injection were inhibited by AT-III pretreatment. The elevated plasma MIP-2 levels were significantly inhibited by AT-III pretreatment compared with vehicle treatment. The inhibitory effect of AT-III on plasma ALT and MIP-2 in Con A-induced liver injury was attenuated by indomethacin (5 mg/kg, ip). Plasma concentration of 6k-PG-F1α at 2 h after AT-III injection was significantly elevated compared with baseline and vehicle pretreatment. Conclusions: These findings suggest that AT-III prevents Con A-induced liver injury through an inhibition of MIP-2 release and a production of prostacyclin