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 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.
Goda
N
N
Department of Biochemistry, School of Medicine, Keio University, Tokyo 160, Japan.
Suzuki
K
K
Naito
M
M
Takeoka
S
S
Tsuchida
E
E
Ishimura
Y
Y
Tamatani
T
T
Suematsu
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D006454:Hemoglobins / Q000008:administration & dosage; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents
D000911:Antibodies, Monoclonal; D006454:Hemoglobins; D007527:Isoenzymes; D008081:Liposomes; D008565:Membrane Proteins; D014662:Vasoconstrictor Agents; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C105245:heme oxygenase-2