Stimulation of DNA synthesis in hepatocytes by Kupffer cells after partial hepatectomy.

The role of Kupffer cells during reparative regeneration of rat liver was investigated with an in vitro experimental model. Conditioned media from primary cultures of Kupffer cells isolated from intact and regenerating liver were added to primary cultures of hepatocytes, and [3H]thymidine incorporation into DNA was studied. Kupffer cell-conditioned media from intact liver and regenerating remnant liver significantly stimulated DNA synthesis in hepatocytes as compared with control media (p less than 0.05). Moreover, the stimulating activity of Kupffer cells prepared from regenerating liver at 6 and 12 hr after partial hepatectomy was significantly higher than that of Kupffer cells from untreated rats (p less than 0.05). The activity was found in serum-free conditioned media. This stimulating activity exponentially increased as the increase of the number of the cultured cells, indicating that the stimulating activity was released directly by cultured Kupffer cells. These results suggest that Kupffer cells stimulate DNA synthesis in hepatocytes by producing and releasing certain factor(s) at an early stage of liver regeneration after partial hepatectomy.