THE ROLE OF KUPFFER CELLS IN THE DIFFERENTIATION PROCESS OF HEPATIC NATURAL-KILLER

Pit cells, or hepatic natural killer (NK) cells, present in rat liver sinusoids, represent an organ-associated NK cell population, with a hi gher level of activation and a different morphology when compared with peripheral blood NK cells, These cells are the result of an influx of peripheral blood NK cells in the liver microenvironment, followed by an activation or differentiation process toward the highly activated p henotype. In this work we investigated the role of Kupffer cells in th is differentiation process of NK cells in the liver sinusoids. In vivo elimination of Kupffer cells with the macrophage cytotoxic drug dichl oromethylene diphosphonate induced a decrease in number of hepatic NK cells that paralleled that of Kupffer cells, This effect was further i nvestigated in vitro. Kupffer cell-conditioned medium appeared to enha nce the viability, tumor-cytotoxic activity, and adherence of hepatic NK cells to liver endothelial cells in vitro. We conclude therefore th at Kupffer cells, present in the microenvironment of the liver sinusoi ds, play an essential role in the differentiation process of periphera l blood NK cells to the highly activated hepatic NK cell population.