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.
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.
Umeda
S
S
Second Department of Pathology, Kumamoto University School of Medicine, Japan.
Takahashi
K
K
Shultz
L D
LD
Naito
M
M
Takagi
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D015152:Blotting, Northern; D001854:Bone Marrow Cells; D002452:Cell Count; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007377:Interleukin-3 / Q000097:blood / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010022:Osteopetrosis / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000737:chemistry / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007377:Interleukin-3; D012333:RNA, Messenger; C036763:monocyte-macrophage differentiation antigen; D016173:Macrophage Colony-Stimulating Factor