Heme oxygenase-1 protects donor livers from ischemia/reperfusion injury: the role of Kupffer cells.
OBJECTIVE
To examine whether heme oxygenase (HO)-1 overexpression would exert direct or indirect effects on Kupffer cells activation, which lead to aggravation of reperfusion injury.


METHODS
Donors were pretreated with cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP), HO-1 inducer and antagonist, respectively. Livers were stored at 4 degrees C for 24 h before transplantation. Kupffer cells were isolated and cultured for 6 h after liver reperfusion.


RESULTS
Postoperatively, serum transaminases were significantly lower and associated with less liver injury when donors were pretreated with CoPP, as compared with the ZnPP group. Production of the cytokines tumor necrosis factor-alpha and interleukin-6 generated by Kupffer cells decreased in the CoPP group. The CD14 expression levels (RT-PCR/Western blots) of Kupffer cells from CoPP-pretreated liver grafts reduced.


CONCLUSIONS
The study suggests that the potential utility of HO-1 overexpression in preventing ischemia/reperfusion injury results from inhibition of Kupffer cells activation.
Zeng
Zhong
Z
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical College, 295 Xichang Road, Kunming 650032, Yunnan Province, China. zzong@medmail.com.cn
Huang
Han-Fei
HF
Chen
Ming-Qing
MQ
Song
Fei
F
Zhang
Yu-Jun
YJ
D000818:Animals; D002478:Cells, Cultured; D019610:Cytoprotection; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D051547:Heme Oxygenase-1