The protective role of Kupffer cells in the ischemia-reperfused rat liver

Takashi Kobayashi, Ken ichiro Hirano, Takashi Yamamoto, Go Hasegawa, Katsuyoshi Hatakeyama, Makoto Suematsu, Makoto Naito

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36 Citations (Scopus)


Kupffer cells constitute a major source of the heme-degrading enzyme, heme oxygenase (HO). This study examined the roles of Kupffer cells in the modulation of accelerated heme catabolism in ischemia-reperfused rat livers. Livers from rats treated with or without liposome-encapsulated dichloromethylene diphosphonate, a Kupffer cell-depleting reagent, underwent a 20-min ligation of the portal vein followed by reperfusion, The time course of the biliary output of bilirubin, the terminal heme-degrading product, and the expression of HO-1 mRNA and protein were monitored. HO-1 mRNA levels were elevated 3 to 12 h after ischemia/reperfusion in both control and Kupffer celldepleted rats. Immunohistochemical analyses of control livers revealed that Kupffer cells expressed high levels of HO-1 while its expression in hepatocytes was low. In Kupffer cell-depleted livers, however, periportal hepatocytes displayed marked HO-1 expression. Under these conditions the two groups exhibited distinct profiles of biliary bilirubin excretion. In the controls, total bilirubin excretion increased 8-fold and peaked at 10 h after ischemia/reperfusion. In contrast, the Kupffer cell-depleting treatment resulted in a significant acceleration of the initial rise in bilirubin production, which peaked at 4 h. However, the total amount of bilirubin excreted within the initial 10 h after reperfusion was reduced by 50% as compared with that of the controls. In Kupffer cell-depleted rats, the levels of GOT and GPT as well as serum endotoxin concentrations were elevated after ischemia/reperfusion. These results suggest that Kupffer cells serve as an ischemia/reperfusion sensor that upregulates heme degradation and bilirubin excretion, and that Kupffer cells protect hepatocytes from gut-derived stressers - including endotoxin-following ischemia/reperfusion.

Original languageEnglish
Pages (from-to)251-261
Number of pages11
JournalArchives of Histology and Cytology
Issue number3
Publication statusPublished - 2002 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Histology


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