REPOPULATION OF MURINE KUPFFER CELLS AFTER INTRAVENOUS ADMINISTRATIONOF LIPOSOME-ENCAPSULATED DICHLOROMETHYLENE DIPHOSPHONATE

Kupffer cells were selectively eliminated in mice by the intravenous a dministration of liposome-entrapped dichloromethylene diphosphonate. A t 5 days, small peroxidase-negative and acid-phosphatase-weakly-positi ve macrophages appeared, increased in number, and differentiated into peroxidase- and acid-phosphatase-positive Kupffer cells Repopulating s mall macrophages actively proliferated, and the number of Kupffer cell s returned to the normal level by day 14, The numbers of macrophage pr ecursors in the fiver as detected by the macroclonal antibodies ER-MP2 0 and ER-MP58 increased after liposome-entrapped dichloromethylene dip hosphonate injection, ER-MP58-positive cells proliferated and differen tiated into ER-MP20-positive cells and eventually into BM8-positive Ku pffer cells in the liver Bone-marrow-derived ER-MP58-positive cells we re also detectable in the liver and differentiated into ER-MP20-positi ve cells, but they did not become BM8-positive macrophages. Macrophage colony-stimulating factor mRNA expression was enhanced in the fiver 1 day after injection. The administration of macrophage colony-stimulat ing factor did not shorten the period of Kupffer cell depletion but in creased the number and the proliferative capacity of repopulating Kupf fer cells. These findings implied that repopulating Kupffer cells are derived from a macrophage precursor pool in the liver rather than fron t bone-marrow-derived monocytes. Local production of macrophage colony -stimulating factor in the liver plays a crucial role in the different iation, maturation, and proliferation of Kupffer cells.