Macrophage colony-stimulating factor is indispensable for repopulation and differentiation of Kupffer cells but not for splenic red pulp macrophages in osteopetrotic (<Emphasis Type="Italic">op</Emphasis>/<Emphasis Type="Italic">op</Emphasis>) mice after macrophage depletion |
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Authors: | Takashi Yamamoto Chikako Kaizu Takashi Kawasaki Go Hasegawa Hajime Umezu Riuko Ohashi Junko Sakurada Shuying Jiang Leonard Shultz Makoto Naito |
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Institution: | (1) Department of Cellular Function, Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan;(2) Division of Pathomorphology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan;(3) Division of Pathology, Niigata University Hospital, Niigata 951-8510, Japan;(4) Department of Immunology, The Jackson Laboratory, Bar Harbor, ME, USA |
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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.
This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture
of Japan, NIH grant CA20408, and a Tsukada Memorial Grant (2000). |
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Keywords: | Macrophage Liposome Dichloromethylene diphosphonate M-CSF Osteopetrotic mouse (op/op) |
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