Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide-mediated microvascular relaxation

The Journal of Clinical Investigation
Nobuhito GodaMakoto Suematsu

Abstract

Carbon monoxide (CO) derived from heme oxygenase has recently been shown to play a role in controlling hepatobiliary function, but intrahepatic distribution of the enzyme is unknown. We examined distribution of two kinds of the heme oxygenase isoforms (HO-1 and HO-2) in rat liver immunohistochemically using monoclonal antibodies. The results showed that distribution of the two isoforms had distinct topographic patterns: HO-1, an inducible isoform, was observed only in Kupffer cells, while HO-2, a constitutive form, distributed to parenchymal cells, but not to Kupffer cells. Both isoforms were undetectable in hepatic stellate cells and sinusoidal endothelial cells. Of the two isoforms, HO-2 in the parenchymal cell rather than HO-1 in the Kupffer cell, appears to play a major role in regulation of microvascular tone. In the perfused liver, administration of HbO2, a CO-trapping reagent that can diffuse across the fenestrated endothelium into the space of Disse, elicited a marked sinusoidal constriction, while administration of a liposome-encapsulated Hb that cannot enter the space had no effect on the microvascular tone. These results suggest that CO evolved by HO-2 in the parenchymal cells, and, released to the extrasinusoidal sp...Continue Reading

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Citations

Jun 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M G Clemens
Aug 8, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y ShinodaY Ishimura
Oct 31, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·N MorikawaM Kitajima
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Sep 19, 2003·Antioxidants & Redox Signaling·Shinji NorimizuMakoto Suematsu
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