Effects of murine recombinant interferon-gamma on rat liver fat storing cell proliferation, cluster formation and proteoglycan synthesis

Rat liver fat storing cells (FSC, perisinusoidal lipocytes, Ito cells) in primary culture were exposed to various concentrations of murine recombinant interferon-gamma (rIFN-gamma) in the range of 1 to 50 units/mL medium for 72 hr. FSC kept in complete medium (10% fetal calf serum) showed a dose-dependent increase of both 3H]thymidine incorporation (up to 2.3-fold) and DNA content of culture. Reverse (inhibitory) effects were obtained with cells kept under serum-reduced (0.5% fetal calf serum) conditions. The synthesis of medium proteoglycans and of total cellular protein was not affected by rIFN-gamma. By bromodeoxyuridine-staining (BrdUrd) and phase contrast microscopy it is shown that rIFN-gamma stimulates strongly the cluster growth of FSC in culture. The cluster forming cells differ in their morphology and their cytoskeleton-staining from typical FSC. They were found to be mostly desmin and alpha-actin negative or weakly positive but highly proliferative. Because no contaminating fibroblasts and other cell types were detected in any appreciable amounts in the early cultures we conclude that the clustered cells might be a rapidly proliferating subpopulation of FSC, which is promoted by rIFN-gamma.