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Effect of Chronic Ethanol Feeding on Kupffer Cell‐Mediated Antitumor Cell Activity
Author(s) -
Kato Shinzo,
Kurose Iwao,
Higuchi Hajime,
Ebinuma Hirotoshi,
Saito Hidetsugu,
Miura Soichiro,
Ishii Hiromasa
Publication year - 1996
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1996.tb01733.x
Subject(s) - kupffer cell , nitric oxide , rhodamine 123 , cell , nitric oxide synthase , cell culture , hepatic stellate cell , chemistry , cell growth , biology , medicine , microbiology and biotechnology , endocrinology , biochemistry , immunology , antibiotics , genetics , multiple drug resistance
We have previously reported that the Kupffer cell has antitumor activity through mitochondrial damage to tumor cells by nitric oxide production. In this study, the effect of chronic ethanol feeding on antihepatoma cell activity of the Kupffer cell was examined in rats. Male rats of the Wistar strain were fed ethanol chronically for 8 weeks by liquid diets. Kupffer cells were isolated from the control rat or the ethanol‐fed rat, and cocultured with AH 70 cells, a rat hepatoma cell line. Fluorescence of rhodamine 123 or propidium iodide was observed as indicators of the mitochondrial damage or cell membrane injury, respectively, by a laser scanning confocal microscopy. Mitochondrial damage of AH 70 cells as indicated by reduction of rhodamine 123 fluorescence was smaller by the coculture with Kupffer cell from the ethanol rat than that from the control. Cell membrane barrier dysfunction of AH 70 cell was less frequently observed with the Kupffer cell from ethanol‐fed rats. A metabolite of nitric oxide (nitrite and nitrate) was less in the cultured medium with the ethanol Kupffer cell than with the control Kupffer cell. Ca 2+ mobilization, which induces inducible nitric oxide synthase and observed by the fluorescence of fluo‐3, in Kupffer cells cocultured with AH 70 cells was suppressed in ethanol‐fed rats. These result suggests that chronic ethanol feeding suppresses antitumor cell activity of Kupffer cell through the impairment of Ca 2+ mobilization and nitric oxide production.