title: Modulation of Kupffer cell and peripheral blood monocyte activity by in vivo treatment of rats with all-trans-retinol.
abstract: Previous studies have shown that large doses of vitamin A potentiate chemical-induced liver injury and that the Kupffer cell is directly involved in this potentiation. Therefore, these studies were designed to determine if Kupffer cells isolated from vitamin A treated male Sprague-Dawley rats (75 mg/kg/day for 3-7 days as all- trans-retinol) had altered activity and function. Respiratory activity of Kupffer cells isolated from rats treated with vitamin A for 3 to 7 days markedly increased. Similarly, phagocytic activity was significantly elevated (up to 9-fold) after exposure to vitamin A for 3 to 7 days. Production of reactive oxygen species, measured by luminol-enhanced chemiluminescence of Kupffer cells isolated after 7 days of vitamin A exposure, was significantly higher than that of control cells when stimulated with opsonized zymosan. Also, the release of superoxide anion by individual Kupffer cells isolated from vitamin A treated rats was nearly three times greater than that of control cells. Basal production of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2) production were significantly elevated in Kupffer cells isolated from rats treated with vitamin A. Lastly, peripheral blood monocytes (PBMC) isolated from rats treated with vitamin A for 7 days had a significantly greater respiratory activity, as well as TNF-alpha and PGE2 production, than PBMC isolated from control rats. Our data suggest that large doses of vitamin A enhance both Kupffer cell and PBMC function. Upregulation of the activity by these phagocytic cells may play a role in the vitamin A potentiation of chemical-induced liver injury.
authors.affiliation: Department of Pharmacology and Toxicology, University of Arizona, Tucson 85721, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Hoglen
authors.forename: E A
authors.initials: EA
authors.lastname: Abril
authors.forename: J M
authors.initials: JM
authors.lastname: Sauer
authors.forename: D L
authors.initials: DL
authors.lastname: Earnest
authors.forename: R S
authors.initials: RS
authors.lastname: McCuskey
authors.forename: R C
authors.initials: RC
authors.lastname: Lantz
authors.forename: S A
authors.initials: SA
authors.lastname: Mobley
authors.forename: I G
authors.initials: IG
authors.lastname: Sipes
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014801:Vitamin A / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D014801:Vitamin A; D015232:Dinoprostone