O2-. release by activated Kupffer cells upon hypoxia-reoxygenation.
Primary cultures of rat liver Kupffer cells generated large amounts of superoxide anion radical (O2-.) when subjected to reoxygenation after a hypoxic period of at least 2 h. O2-. formation reached its maximum rate of approximately 25 nmol/10(6) cells within 1 h after reoxygenation. Two to four hours after reoxygenation, the number of injured cells began to increase and after 10 h approximately 60% of the cells were dead. During the period of O2-. release no significant difference in cell viability was observed between reoxygenated and hypoxically incubated cells, indicating a distinct time lag between O2-. release and onset of cell damage. Addition of diphenyliodonium, a specific inhibitor of the neutrophilic NADPH oxidase, to the Kupffer cells just before reoxygenation diminished both O2-. formation and cell injury up to 70%. Reoxygenation injury was completely prevented when superoxide dismutase and catalase were added immediately before reoxygenation. The results indicate that Kupffer cells subjected to hypoxia-reoxygenation generate a burst of reactive oxygen species and that this kind of "activation," probably by activating the NADPH oxidase, contributes to the self-destruction of the cells.
Rymsa
B
B
Klinische Forschergruppe Leberschädigung, Institut für Physiologische Chemie I, Heinrich-Heine-Universität, Düsseldorf, Federal Republic of Germany.
Wang
J F
JF
de Groot
H
H
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005609:Free Radicals; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D007477:Ions; D007728:Kupffer Cells / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
D001713:Biphenyl Compounds; D005609:Free Radicals; D007477:Ions; D009861:Onium Compounds; C031291:diphenyliodonium; D013481:Superoxides; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen