Faculty Research 1990 - 1999

Effects of macrophage colony-stimulating factor on macrophages and their related cell populations in the osteopetrosis mouse defective in production of functional macrophage colony-stimulating factor protein.

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Antibodies-Monoclonal: an, Antigens-Differentiation: an, Blotting-Northern, Bone-Marrow: cy, Cell-Count, Flow-Cytometry, Immunohistochemistry, Interleukin-3: bl, ge, Liver: pa, Macrophage-Colony-Stimulating-Factor: df, Macrophages: de, im, ul, Mice, Mice-Inbred-C57BL, Mice-Mutant-Strains, Microscopy-Electron, Monocytes: de, im, Osteopetrosis: pp, pa, RNA-Messenger: an, Spleen: pa, Stem-Cells: de, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

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Am J Pathol 1996 Aug;149(2):559-74




The development of macrophage populations in osteopetrosis (op) mutant mice defective in production of functional macrophage colony-stimulating factor (M-CSF) and the response of these cell populations to exogenous M-CSF were used to classify macrophages into four groups: 1) monocytes, monocyte-derived macrophages, and osteoclasts, 2) MOMA-1-positive macrophages, 3) ER-TR9-positive macrophages, and 4) immature tissue macrophages. Monocytes, monocyte-derived macrophages, osteoclasts in bone, microglia in brain, synovial A cells, and MOMA-1- or ER-TR9-positive macrophages were deficient in op/op mice. The former three populations expanded to normal levels in op/op mice after daily M-CSF administration, indicating that they are developed and differentiated due to the effect of M-CSF supplied humorally. In contrast, the other cells did not respond or very slightly responded to M-CSF, and their development seems due to either M-CSF produced in situ or expression of receptor for M-CSF. Macrophages present in tissues of the mutant mice were immature and appear to be regulated by either granulocyte/macrophage colony-stimulating factor and/or interleukin-3 produced in situ or receptor expression. Northern blot analysis revealed different expressions of GM-CSF and IL-3 mRNA in various tissues of the op/op mice. However, granulocyte/macrophage colony-stimulating factor and interleukin-3 in serum were not detected by enzyme-linked immunosorbent assay. The immature macrophages differentiated and matured into resident macrophages after M-CSF administration, and some of these cells proliferated in response to M-CSF.