Repopulation of Kupffer cells in op/op mice after administration of liposome-encapsulated dichloromethylene diphosphonate

Abstract

Kupffer cells were selectively eliminated in the macrophage colony stimulating factor (M-CSF)-deficient osteopetrotic (op/op) mice by intravenous administration of liposome-entrapped dichloromethylene diphosphonate. Repopulation of Kupffer cells was observed in the Kupffer cell-depleted littermate mouse (op/+) liver by 14 days after treatment. In contrast, repopulation of Kupffer cells was not observed in the Kupffer cell-depleted op/op mice through the observation period of 56 days. Daily administration of M-CSF induced remarkable repopulation of Kupffer cells and proliferation of macrophage precursor cells, whereas GM-CSF and IL-3 were less effective. These findings indicated that M-CSF plays a major role in Kupffer cell development.