Induction in interferon-alpha/beta-treated hepatocytes of the inhibitor of the multiplication of IFN-alpha/beta-resistant Friend leukemia cells.

Abstract

We reported previously that interferon-alpha/beta (IFN-alpha/beta)-treated hepatocytes in culture released a soluble factor(s) that suppressed the multiplication of an INF-alpha/beta-resistant clone of Friend leukemia cells (FLCs). To characterize the factor(s) further, we first examined the possibility that products of nonparenchymal cells (NPCs) included in small number in the hepatocyte cultures were involved in the inhibitory activity. We prepared cultures of purified adherent NPCs, mostly Kupffer cells, and sinusoidal endothelial cells, and culture supernatants of NPCs pretreated with IFN-alpha/beta were tested for the inhibitory activity for FLC multiplication. IFN did not induce any inhibitory activity in NPC cultures, whereas LPS-stimulated NPCs cultivated in parallel released several inhibitory factors including tumor necrosis factor-alpha (TNF-alpha). To explore the possibility that IFN augmented the release of hepatocyte cytosolic proteins, including arginase, we compared the inhibitory activity in culture supernatant of IFN-treated hepatocytes with that found in hepatocyte extract by anion-exchange chromatography. The IFN-induced inhibitory activity was eluted at relatively high salt concentration as a single peak, while the inhibitory activity in hepatocyte extract was co-eluted with arginase at low salt concentration. These results suggested that IFN induced production by hepatocytes of an inhibitor of FLC multiplication.