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

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 immunohistochemical...

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Bibliographic Details
Published in:The Journal of clinical investigation 1998-02, Vol.101 (3), p.604-612
Main Authors: Goda, N, Suzuki, K, Naito, M, Takeoka, S, Tsuchida, E, Ishimura, Y, Tamatani, T, Suematsu, M
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - metabolism
Carbon Monoxide - metabolism
Cells, Cultured
Female
Heme Oxygenase (Decyclizing) - biosynthesis
Heme Oxygenase (Decyclizing) - genetics
Heme Oxygenase-1
Hemoglobins - administration & dosage
Isoenzymes - biosynthesis
Isoenzymes - genetics
Liposomes
Liver - cytology
Liver - metabolism
Male
Membrane Proteins
Mice
Mice, Inbred BALB C
Rats
Rats, Wistar
Vasoconstrictor Agents
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Summary: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 space, served as the physiological relaxant for hepatic sinusoids.
ISSN:0021-9738
DOI:10.1172/jci1324