MODULATION OF KUPFFER CELL AND PERIPHERAL-BLOOD MONOCYTE ACTIVITY BY IN-VIVO TREATMENT OF RATS WITH ALL-TRANS-RETINOL

Previous studies have shown that large doses of vitamin A potentiate c hemical-induced liver injury and that the Kupffer cell is directly inv olved in this potentiation. Therefore, these studies were designed to determine if Kupffer cells isolated from vitamin A treated male Spragu e-Dawley rats (75 mg/kg/day for 3-7 days as all-tians-retinol) had alt ered activity and function. Respiratory activity of Kupffer cells isol ated from rats treated with vitamin A for 3 to 7 days markedly increas ed. Similarly, phagocytic activity was significantly elevated (up to 9 -fold) after exposure to vitamin A for 3 to 7 days. Production of reac tive oxygen species, measured by luminol-enhanced chemiluminescence of Kupffer cells isolated after 7 days of vitamin A exposure, was signif icantly higher than that of control cells when stimulated with opsoniz ed zymosan. Also, the release of superoxide anion by individual Kupffe r cells isolated from vitamin A treated rats was nearly three times gr eater than that of control cells. Basal production of tumor necrosis f actor-alpha (TNF-alpha) and prostaglandin E2 (PGE(2)) production were significantly elevated in Kupffer cells isolated from rats treated wit h vitamin A. Lastly, peripheral blood monocytes (PBMC) isolated from r ats treated with vitamin A for 7 days had a significantly greater resp iratory activity, as well as TNF-alpha and PGE(2) production, than PBM C isolated from control rats. Our data suggest that large doses of vit amin A enhance both Kupffer cell and PBMC function. Upregulation of th e activity by these phagocytic cells may play a role in the vitamin A potentiation of chemical-induced liver injury.