Nitric oxide mediates mitochondrial dysfunction in hepatoma cells induced by non‐activated Kupffer cells: Evidence implicating ICAM‐1‐dependent process

IWAO KUROSE, HIROTOSHI EBINUMA, HAJIME HIGUCHI, YOSHIKAZU YONEI, HIDETSUGU SAITO, SHINZO KATO, SOICHIRO MIURA, HIROMASA ISHII

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The metabolic changes in a rat hepatoma cell line, AH70 cells, after co‐culture with rat Kupffer cells (KC) were visualized and analysed using a fluorescence microscope equipped with a silicon intensified target camera and a laser scanning confocal microscopic system. Kupffer cells were isolated from male Wistar rats, and cultured without any stimuli. The non‐activated KC reduced the mitochondrial energization in the cocultured AH70 cells within 2 h, which was indicated by decreased rhodamine 123 (Rh123) fluorescence. Either Ng‐monomethyl‐l‐arginine or dexamethasone significantly attenuated the KC‐induced mitochondrial dysfunction in AH70 cells, suggesting the involvement of nitric oxide (NO) derived from inducible‐type nitric oxide synthase (iNOS). Administration of monoclonal antibody (mAb) directed against rat ICAM‐1 also prevented the decrease in Rh123 fluorescence. Electron microscopy revealed that the membrane‐to‐membrane attachment between KC and AH70 cells occurred within 2 h. A laser scanning confocal microscopic observation using mAb against ICAM‐1 presented that the ICAM‐1 expression on AH70 cells and KC increased after the co‐culture. It is therefore concluded that the KC‐mediated mitochondrial dysfunction of hepatoma cells largely depends on NO production by iNOS. Furthermore, the present study supports a scenario that the NO production and release from KC is triggered by the close contact with hepatoma cells through adhesion molecules such as ICAM‐1.

Original languageEnglish
Pages (from-to)S68-S71
JournalJournal of Gastroenterology and Hepatology
Volume10
Issue number1 S
DOIs
Publication statusPublished - 1995 Sep

Keywords

  • CD 18
  • Key words:
  • N‐monomethyl‐l‐arginine (L‐NMMA)
  • dexamethasone
  • laser scanning confocal microscopy
  • transmission electron microscope

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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