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

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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
Volume65
Issue number3
Publication statusPublished - 2002 Aug

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Kupffer Cells
Ischemia
Reperfusion
Bilirubin
Liver
Heme Oxygenase-1
Heme
Hepatocytes
Endotoxins
Heme Oxygenase (Decyclizing)
Messenger RNA
Portal Vein
Ligation
Up-Regulation

ASJC Scopus subject areas

  • Anatomy
  • Histology

Cite this

Kobayashi, T., Hirano, K. I., Yamamoto, T., Hasegawa, G., Hatakeyama, K., Suematsu, M., & Naito, M. (2002). The protective role of Kupffer cells in the ischemia-reperfused rat liver. Archives of Histology and Cytology, 65(3), 251-261.

The protective role of Kupffer cells in the ischemia-reperfused rat liver. / Kobayashi, Takashi; Hirano, Ken ichiro; Yamamoto, Takashi; Hasegawa, Go; Hatakeyama, Katsuyoshi; Suematsu, Makoto; Naito, Makoto.

In: Archives of Histology and Cytology, Vol. 65, No. 3, 08.2002, p. 251-261.

Research output: Contribution to journalArticle

Kobayashi, T, Hirano, KI, Yamamoto, T, Hasegawa, G, Hatakeyama, K, Suematsu, M & Naito, M 2002, 'The protective role of Kupffer cells in the ischemia-reperfused rat liver', Archives of Histology and Cytology, vol. 65, no. 3, pp. 251-261.
Kobayashi T, Hirano KI, Yamamoto T, Hasegawa G, Hatakeyama K, Suematsu M et al. The protective role of Kupffer cells in the ischemia-reperfused rat liver. Archives of Histology and Cytology. 2002 Aug;65(3):251-261.
Kobayashi, Takashi ; Hirano, Ken ichiro ; Yamamoto, Takashi ; Hasegawa, Go ; Hatakeyama, Katsuyoshi ; Suematsu, Makoto ; Naito, Makoto. / The protective role of Kupffer cells in the ischemia-reperfused rat liver. In: Archives of Histology and Cytology. 2002 ; Vol. 65, No. 3. pp. 251-261.
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