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.
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