The role of Kupffer cells during reparative regeneration of rat liver was investigated with an in uitro 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 < 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 < 0.05). The activity was found in serumfree 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.
Mammalian liver shows a remarkable regenerative capacity after partial hepatectomy (1 1. Various effectors, e.g. humoral factors (2-4), portal blood factors (i.e. insulin and glucagon) (5-7), and liver-derived growth factors (8-10) are known to stimulate liver regeneration in in. uiuo experimental models. Several investigators suggested that t h e reticuloendothelial system ( R E S ) plays an important regulatory role in regeneration of rat liver.
The blockade of the RES depressed t h e hepatocellular proliferation after partial hepatectomy (1 1-13). In contrast, Rikkers and Newton (14) found n o major effect of