CD18/ICAM-1-dependent nitric oxide production of Kupffer cells as a cause of mitochondrial dysfunction in hepatoma cells: Influence of chronic alcohol feeding

Iwao Kurose, Hajime Higuchi, Naoyuki Watanabe, Soichiro Miura, Kengo Tomita, Yoshikazu Yonei, Masaaki Takaishi, Shigeyuki Zeki, Tetsuya Nakamura, Hidetsugu Saito, Shinzo Kato, Hiromasa Ishii

研究成果: Article査読

6 被引用数 (Scopus)

抄録

The present study was designed to monitor the process for hepatoma cell injury induced by Kupffer cells. The non-activated Kupffer cells isolated from male Wistar rats reduced the mitochondrial membrane potential in the cocultured AH70 cells, which was indicated by the decreased rhodamine 123 (Rh123) fluorescence. Increased level of nitrite and nitrate in the medium and induction of iNOS in Kupffer cells were observed after coculture with AH70 cells. Incubation with either N(G)-monomethyl-L-arginine or aminoguanidine attenuated the increased nitric oxide (NO) production of Kupffer cells and the decreased Rh123 fluorescence of AH70 cells. Fluo-3, a calcium-sensitive probe, fluorescence in Kupffer cells increased after coculture with AH70 cells. Addition of TMB-8, a calcium inhibitor, or monoclonal antibody directed against ICAM-1 or CD18 prevented the increases in fluo-3 fluorescence and NO production of Kupffer cells and Kupffer cell- induced mitochondrial dysfunction in AH70 cells, suggesting the involvement of calcium mobilization and CD18/ICAM-1. It is therefore suggested that the Kupffer cell-mediated mitochondrial dysfunction of hepatoma cells largely depends on NO production by iNOS, and that the NO production by Kupffer cells is triggered by CD18/ICAM-1-dependent interaction with hepatoma cells and subsequent calcium mobilization. In other series of experiments, male Wistar rats fed ethanol for 4 weeks were used. The NO production and calcium mobilization of Kupffer cells and reduction of the mitochondrial membrane potential in cocultured hepatoma cells were diminished in the case of Kupffer cells isolated from chronically ethanol-fed rats, while CD18 and ICAM-1 expression was still observed. Thus, the present study further suggests that NO-dependent anti-hepatoma cell activity of Kupffer cells is suppressed in chronically ethanol-fed animals.

本文言語English
ページ(範囲)229-239
ページ数11
ジャーナルFree Radical Biology and Medicine
22
1-2
DOI
出版ステータスPublished - 1997
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 生理学(医学)

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