In order to investigate the hematolymphoid system in the adult murine liver, we examined colony-stimulating factor (CSF) released from primary cultured liver cell fractions, parenchymal and nonparenchymal liver cells (more than 99% pure. Using a fibrin clot culture system, we found colony-stimulating activity not only in the culture supernatant from nonparenchymal fraction of normal liver cells (NP-NLC sup), but also in the culture supernatant from parenchymal fraction of normal liver cells (P-NLC sup). Clusters and colonies, which were generated in 4-day cultures of bone marrow cells or spleen cells with P-NLC sup or NP-NLC sup, were mainly composed of granulocytes (G), macrophages (M), and granulocytes and macrophages (GM). Both P-NLC sup and NP-NLC sup proliferated IC2, which is a GM-CSF and IL-3 dependent cell line, and this proliferation was completely inhibited by rabbit anti-murine GM-CSF antibody. Furthermore, both Northern blot analysis and in situ hybridization with specific cDNA probe for murine GM-CSF showed that parenchymal liver cells expressed GM-CSF mRNA transcripts. The present findings indicate that cultured murine parenchymal liver cells produce GM-CSF. The possibility, therefore, is suggested that parenchymal liver cells also play an important role in the regional hematolymphoid system of the liver.

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PubMedDate not supplied

Effects of clarithromycin and its metabolites on the mixed function oxidase system in hepatic microsomes of rats.

Clarithromycin and its metabolites have been examined for their abilities to induce specific form(s) of cytochrome P-450 and metabolite complex formation in rats. Pretreatment of rats with clarithromycin,N-demethyl clarithromycin, clarithromycin N-oxide, and decladinosyl clarithromycin resulted in 48-75% decreases in the amount of 2C11 and 100-600% increases in the amount of 3A1. Clarithromycin and N-demethyl clarithromycin, but not decladinosyl clarithromycin, produced a metabolite complex with cytochrome P-450 in vivo. Activities of testosterone 2 beta- and 6 beta-hydroxylases were increased by administration of clarithromycin and N-demethyl clarithromycin when these activities were measured in the presence of ferricyanide, but not significant induction was observed when measured in the absence of ferricyanide. Clarithromycin N-oxide treatment resulted in the increase in hydroxylation of testosterone not only at the 2 beta- and 6 beta-positions (430 and 190%, respectively), but also at 7 alpha-position (60%), regardless of the presence or absence of ferricyanide. In vitro experiments with hepatic microsomes of dexamethasone-pretreated rats indicated that the metabolites that were modified at the tertiary amino group more efficiently produced the metabolite complex with cytochrome P-450 compared with the parent compound. In contrast, decladinosyl and hydroxylated metabolites had similar or lower capacities for metabolite complex formation than did the parent compound. Clarithromycin and its N-modified metabolites were able to induce 3A1 and form a metabolite complex with cytochrome P-450 in vivo in varying extents. Decladinosyl clarithromycin has a weak inducibility of 3A1 and did not form a metabolite complex with cytochrome P-450 in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

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