Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18

Hidetsugu Saito, Iwao Kurose, Hirotoshi Ebinuma, Dai Fukumura, Hajime Higuchi, Kazuhiro Atsukawa, Shinichiro Tada, Hiroyuki Kimura, Yoshikazu Yonei, Tetsuya Masuda, Soichiro Miura, Hiromasa Ishii

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17 Citations (Scopus)


Rat Kupffer cell (KC)-mediated cytotoxicity against both the syngeneic hepatoma cell line AH70 and hepatocytes was evaluated by changes in mitochondrial function, and the possible role of ICAM-1/CD18 in the interaction between the cells was studied. Rhodamine 123 fluorescence, a marker of the mitochondrial membrane potential, decreased in AH70 cells after co-culture with KC, while that in hepatocytes was unchanged by co-culture. This decrease was blocked by anti-ICAM-1, anti-CD18 and the inhibition of nitric oxide synthesis. Cytometric studies demonstrated that ICAM-1 expression on AH70 cells increased after addition of IFN-γ, IL-1β, tumor necrosis factor (TNF)-α or KC, while in hepatocytes ICAM-1 was not increased. Anti-ICAM-1 pretreatment inhibited the increase in ICAM-1 expression and the decrease in rhodamine 123 fluorescence on AH70 cells after co-culture with KC. CD18 on KC was increased only after co-culture with AH70. TNF-α but not IFN-γ was detected in the supernatant of co-culture between KC and AH70 cells, and this production was partially inhibited by anti-ICAM-1 and anti-CD18. The activity of inducible nitric oxide synthase in Kupffer cells and the levels of nitrites and nitrates in the co-culture supernatant increased over time, and this increase was attenuated either by addition of NO synthesis inhibitors, anti-ICAM-1 or anti-CD18. These results indicate that the rat KC causes mitochondrial dysfunction in cancer cells via the production of NO and cell-to-cell adhesion via ICAM-1/CD18 has an important role in this cytotoxic process.

Original languageEnglish
Pages (from-to)1165-1172
Number of pages8
JournalInternational immunology
Issue number7
Publication statusPublished - 1996
Externally publishedYes


  • CD18
  • Confocal microscopy
  • Cytotoxicity
  • Flow cytometry
  • ICAM-1
  • Kupffer cell
  • Nitric oxide
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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