Kupffer cell exacerbation of hepatocyte hypoxia/reoxygenation injury.
In order to examine the possible contribution of the Kupffer cell to the generation of hypoxia/reoxygenation injury in the liver, primary cultures of hepatocytes, either alone or in coculture with Kupffer cells, were exposed to 90 min of sublethal hypoxia followed by 120 min of reoxygenation. Prolonged incubation of cocultured hepatocytes and Kupffer cells resulted in increased release of lactic dehydrogenase (LDH) indicating cell injury even under normoxic conditions. LDH release was further increased by the presence of Kupffer cells during hypoxia/reoxygenation. To determine whether or not this effect of Kupffer cells might be the result of oxygen-derived free radical production, we assessed the efficacy of the enzymatic scavengers superoxide dismutase (SOD) + catalase in ameliorating the Kupffer cell mediated injury. SOD + catalase was effective in preventing free radical injury generated by hypoxanthine + xanthine oxidase. However, SOD + catalase did not ameliorate hepatocyte injury caused by Kupffer cells. Thus, activation of Kupffer cells may be an important factor in the genesis of liver injury, but the mediator of Kupffer cell exacerbation of hepatocyte injury appears to be a mechanism other than free radicals released into the medium. These results indicate that chemical substances from the activated Kupffer cells may cause hepatocyte damage, which cannot be blocked by SOD + catalase, and suggest that these substances at reflow may be important for the genesis of reperfusion injury in vivo.
Kobayashi
S
S
Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Clemens
M G
MG
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D007728:Kupffer Cells / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
D007770:L-Lactate Dehydrogenase