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 language | English |
|---|---|
| Pages (from-to) | 1165-1172 |
| Number of pages | 8 |
| Journal | International Immunology |
| Volume | 8 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 1996 |
Fingerprint
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 journal › Article
}
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 -