Effects of recombinant human macrophage colony-stimulating factor on proliferation, differentiation and survival of Kupffer cells in the liver of adult mice

OBJECTIVE: To investigate the effects of macrophage colony-stimulating fact or (NI-CSF) on the proliferation, differentiation and survival of Kupffer c ells in the liver of adult mice. STUDY DESIGN: By the combined method of autoradiography with [H-3]thymidine and immunohistochemistry using a monoclonal antibody against mouse macroph ages (F4/80 or BM8), the labeling rate of [H-3]thymidine in macrophages wit hin the liver sinusoids was examined at various intervals after single flas h labeling with [H-3]thymidine in adult mice with or without daily administ ration of recombinant human M-CSF. RESULTS: A minor population of Kupffer cells (about 2%) possessed prolifera tive capacity under a normal steady state condition. With time after flash labeling, the influx of monocytes and their differentiation into macrophage s were demonstrated in the liver, and their labeling rate returned to the b aseline level one week later. After ward, the labeling rate of Kupffer cell s was maintained at the baseline level until the end of five weeks. Adminis tration of M-CSF enhanced the proliferative capacity of Kupffer cells, incr eased the number of macrophages and delayed the time of peaking. However, i t did not prolong the survival of Kupffer cells. CONCLUSION: In normal mice, Kupffer cells can survive for at least five wee ks. Daily M-CSF administration induces the increased number and proliferati ve capacity of Kupffer cells.