title: Macrophage colony-stimulating factor is indispensable for repopulation and differentiation of Kupffer cells but not for splenic red pulp macrophages in osteopetrotic (op/op) mice after macrophage depletion.
abstract: We previously reported that macrophage colony-stimulating factor (M-CSF, CSF-1) played important roles in the process of the repopulation of Kupffer cells after their elimination by administration of liposome-entrapped dichloromethylene diphosphonate (lipo-MDP). In this study, we examined the repopulation of Kupffer cells and splenic red pulp macrophages in osteopetrotic (op/op) mice defective in the production of functional M-CSF and their littermate mice by using the lipo-MDP model. In untreated op/op mice, numbers of F4/80-positive Kupffer cells in the liver and F4/80-positive splenic red pulp macrophages were reduced. Repopulation of Kupffer cells and splenic macrophages was observed in littermate (op/+) mice liver by 14 days after depletion. However, in op/op mice, repopulation of Kupffer cells was not observed in Kupffer-cell-depleted op/op mice until 56 days after depletion, whereas splenic red pulp macrophages repopulated and recovered to the level of control op/op mice by 10 days after depletion. Single injection of M-CSF was effective for the induction of the repopulation of Kupffer cells, and daily administration of M-CSF induced remarkable repopulation and maturation of Kupffer cells and proliferation of macrophage precursor cells in the liver of Kupffer-cell-depleted op/op mice. These results suggest that Kupffer cells are completely M-CSF-dependent tissue macrophages, whereas splenic red pulp macrophages are composed of M-CSF-dependent macrophages and M-CSF-independent macrophages. This mouse model provides a useful tool for the study of effects of growth factor on Kupffer cell differentiation in vivo.
authors.affiliation: Department of Cellular Function, Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan, ty@med.niigata-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Chikako
authors.initials: C
authors.lastname: Kaizu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Go
authors.initials: G
authors.lastname: Hasegawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Umezu
authors.forename: Riuko
authors.initials: R
authors.lastname: Ohashi
authors.forename: Junko
authors.initials: J
authors.lastname: Sakurada
authors.forename: Shuying
authors.initials: S
authors.lastname: Jiang
authors.forename: Leonard
authors.initials: L
authors.lastname: Shultz
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002454:Cell Differentiation; D004002:Clodronic Acid / Q000494:pharmacology; D007728:Kupffer Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D008081:Liposomes; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008264:Macrophages / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D010022:Osteopetrosis / Q000473:pathology* / Q000503:physiopathology; D013154:Spleen / Q000166:cytology* / Q000276:immunology
chemical_list: D050071:Bone Density Conservation Agents; D008081:Liposomes; D004002:Clodronic Acid; D016173:Macrophage Colony-Stimulating Factor