Role of heme oxygenase-1 and kupffer cells in the production of bilirubin in the rat liver

K. I. Hirano, T. Kobayashi, T. Watanabe, T. Yamamoto, G. Hasegawa, K. Hatakeyama, M. Suematsu, M. Naito

Research output: Contribution to journalArticle

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Abstract

Heme oxygenase (HO)-1, the heme-degrading enzyme in macrophages, plays a key role in bilirubin metabolism. HO-1 is expressed in various tissue macrophages, especially Kupffer cells. This study aimed to examine the roles of macrophages and HO-1 in the modulation of heme catabolism in rat livers. Rats treated with or without liposome-encapsulated dichloromethylene diphosphonate, a macrophage-depleting reagent, were administered with heat-denatured red blood cells (h-RBC), and the time course of the biliary output of bilirubin and the expressions of HO-1 mRNA and protein were monitored. Immunohistochemistry in the control rat liver revealed that Kupffer cells constitute a major cellular component expressing HO-1, while hepatocytes exhibited little expression. The levels of HO-1 expression in Kupffer cells were elevated immediately after injection of h-RBC. In Kupffer cell-depleted livers, however, HO-l-expressing cells were not detected even after h-RBC administration. HO-1 mRNA levels were elevated at 2 h after administration of h-RBC in control rat livers, while they were very low in Kupffer cell-depleted rat livers. The control and Kupffer cell-depleted groups exhibited distinct time courses of biliary bilirubin excretion. In the untreated control rats, total bilirubin excretion increased about two-fold at 5 h after h-RBC administration. In contrast, the Kupffer cell-depleting treatment decreased the level of bilirubin production; administration of h-RBC to Kupffer cell-depleted rats did not accelerate the generation of bilirubin. These results suggest that Kupffer cells serve both as a sensor for scenesent RBC clearance and an effector that upregulates heme-degrading capacity and bilirubin production.

Original languageEnglish
Pages (from-to)169-178
Number of pages10
JournalArchives of Histology and Cytology
Volume64
Issue number2
Publication statusPublished - 2001

Fingerprint

Heme Oxygenase-1
Kupffer Cells
Bilirubin
Liver
Hot Temperature
Erythrocytes
Heme
Macrophages
Heme Oxygenase (Decyclizing)
Messenger RNA
Hepatocytes
Up-Regulation
Immunohistochemistry
Injections

ASJC Scopus subject areas

  • Anatomy
  • Histology

Cite this

Hirano, K. I., Kobayashi, T., Watanabe, T., Yamamoto, T., Hasegawa, G., Hatakeyama, K., ... Naito, M. (2001). Role of heme oxygenase-1 and kupffer cells in the production of bilirubin in the rat liver. Archives of Histology and Cytology, 64(2), 169-178.

Role of heme oxygenase-1 and kupffer cells in the production of bilirubin in the rat liver. / Hirano, K. I.; Kobayashi, T.; Watanabe, T.; Yamamoto, T.; Hasegawa, G.; Hatakeyama, K.; Suematsu, M.; Naito, M.

In: Archives of Histology and Cytology, Vol. 64, No. 2, 2001, p. 169-178.

Research output: Contribution to journalArticle

Hirano, KI, Kobayashi, T, Watanabe, T, Yamamoto, T, Hasegawa, G, Hatakeyama, K, Suematsu, M & Naito, M 2001, 'Role of heme oxygenase-1 and kupffer cells in the production of bilirubin in the rat liver', Archives of Histology and Cytology, vol. 64, no. 2, pp. 169-178.
Hirano KI, Kobayashi T, Watanabe T, Yamamoto T, Hasegawa G, Hatakeyama K et al. Role of heme oxygenase-1 and kupffer cells in the production of bilirubin in the rat liver. Archives of Histology and Cytology. 2001;64(2):169-178.
Hirano, K. I. ; Kobayashi, T. ; Watanabe, T. ; Yamamoto, T. ; Hasegawa, G. ; Hatakeyama, K. ; Suematsu, M. ; Naito, M. / Role of heme oxygenase-1 and kupffer cells in the production of bilirubin in the rat liver. In: Archives of Histology and Cytology. 2001 ; Vol. 64, No. 2. pp. 169-178.
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