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

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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
Volume8
Issue number7
DOIs
Publication statusPublished - 1996

Fingerprint

Kupffer Cells
Intercellular Adhesion Molecule-1
Hepatocellular Carcinoma
Nitric Oxide
Coculture Techniques
Rhodamine 123
Hepatocytes
Tumor Necrosis Factor-alpha
Fluorescence
Mitochondrial Membrane Potential
Nitric Oxide Synthase Type II
Nitrites
Interleukin-1
Cell Adhesion
Cell Communication
Nitrates
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18. / Saito, Hidetsugu; Kurose, Iwao; Ebinuma, Hirotoshi; Fukumura, Dai; Higuchi, Hajime; Atsukawa, Kazuhiro; Tada, Shinichiro; Kimura, Hiroyuki; Yonei, Yoshikazu; Masuda, Tetsuya; Miura, Soichiro; Ishii, Hiromasa.

In: International Immunology, Vol. 8, No. 7, 1996, p. 1165-1172.

Research output: Contribution to journalArticle

Saito, H, Kurose, I, Ebinuma, H, Fukumura, D, Higuchi, H, Atsukawa, K, Tada, S, Kimura, H, Yonei, Y, Masuda, T, Miura, S & Ishii, H 1996, 'Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18', International Immunology, vol. 8, no. 7, pp. 1165-1172. https://doi.org/10.1093/intimm/8.7.1165
Saito, Hidetsugu ; Kurose, Iwao ; Ebinuma, Hirotoshi ; Fukumura, Dai ; Higuchi, Hajime ; Atsukawa, Kazuhiro ; Tada, Shinichiro ; Kimura, Hiroyuki ; Yonei, Yoshikazu ; Masuda, Tetsuya ; Miura, Soichiro ; Ishii, Hiromasa. / Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18. In: International Immunology. 1996 ; Vol. 8, No. 7. pp. 1165-1172.
@article{2dcbbd483f874b5592d400ad0a81d2fa,
title = "Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18",
abstract = "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.",
keywords = "CD18, Confocal microscopy, Cytotoxicity, Flow cytometry, ICAM-1, Kupffer cell, Nitric oxide, Nitric oxide synthase",
author = "Hidetsugu Saito and Iwao Kurose and Hirotoshi Ebinuma and Dai Fukumura and Hajime Higuchi and Kazuhiro Atsukawa and Shinichiro Tada and Hiroyuki Kimura and Yoshikazu Yonei and Tetsuya Masuda and Soichiro Miura and Hiromasa Ishii",
year = "1996",
doi = "10.1093/intimm/8.7.1165",
language = "English",
volume = "8",
pages = "1165--1172",
journal = "International Immunology",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "7",

}

TY - JOUR

T1 - Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18

AU - Saito, Hidetsugu

AU - Kurose, Iwao

AU - Ebinuma, Hirotoshi

AU - Fukumura, Dai

AU - Higuchi, Hajime

AU - Atsukawa, Kazuhiro

AU - Tada, Shinichiro

AU - Kimura, Hiroyuki

AU - Yonei, Yoshikazu

AU - Masuda, Tetsuya

AU - Miura, Soichiro

AU - Ishii, Hiromasa

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

KW - CD18

KW - Confocal microscopy

KW - Cytotoxicity

KW - Flow cytometry

KW - ICAM-1

KW - Kupffer cell

KW - Nitric oxide

KW - Nitric oxide synthase

UR - http://www.scopus.com/inward/record.url?scp=8944249287&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8944249287&partnerID=8YFLogxK

U2 - 10.1093/intimm/8.7.1165

DO - 10.1093/intimm/8.7.1165

M3 - Article

C2 - 8757962

AN - SCOPUS:8944249287

VL - 8

SP - 1165

EP - 1172

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 7

ER -