Carbon monoxide (CO) derived from heme oxygenase has been shown to play a role in controlling hepatobiliary function (J. Clin. Invest. 96, 1995), 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 newly raised monoclonal antibodies. Mouse T cell lines (WR19L) transfected with rat HO-1 and HO-2 cDNAs were established, and BALB/c mice were injected with their microsomal fractions to obtain B lymphocytes for development of antibody-producing hybridomas. Monoclonal antibodies against HO-1 and -2 obtained by this method were named GTS-1 and GTS-2, respectively, and no crossreactivity was evident as assessed by Western blotting analysis using cell lysates from rHO-1 and rHO-2 transfectant cells. 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 nor sinusoidal endothelial cells. These results indicate that CO endogenously generated by the HO reaction is derived not only from the intrasinusoidal compartment (Kupffer cells), but also from the extrasinusoidal space (parenchymal cells), and thus shed light on microtopographic basis for CO-mediated vasorelaxing mechanisms in the liver.
|出版ステータス||Published - 1998 3月 20|
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