Production of granulocyte-macrophage colony-stimulating factor by adult murine parenchymal liver cells (hepatocytes).

Abstract

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.