title: Effects of macrophage colony-stimulating factor (M-CSF) on the development, differentiation, and maturation of marginal metallophilic macrophages and marginal zone macrophages in the spleen of osteopetrosis (op) mutant mice lacking functional M-CSF activity.
abstract: Immunohistochemical techniques using an anti-mouse panmacrophage monoclonal antibody and anti-mouse monoclonal antibodies specific for marginal metallophilic macrophages or marginal zone macrophages were used to detect red pulp macrophages, marginal metallophilic macrophages, and marginal zone macrophages in the spleen of op/op mice. In the mutant mice, the red pulp macrophages were reduced to about 60% of those in the normal littermates and the marginal metallophilic macrophages and marginal zone macrophages were absent. After administration of recombinant human macrophage colony-stimulating factor (rhM-CSF), numbers of red pulp macrophages increased rapidly, reaching levels found in normal littermates 1 week later. In contrast, the marginal metallophilic macrophages as well as the marginal zone macrophages appeared slowly after rhM-CSF administration and their numbers were less than half of the baseline level of normal littermates even at 12 weeks of administration. The distribution of marginal metallophilic macrophages and marginal zone macrophages appearing after M-CSF administration was irregular in the spleen of the op/op mice. These splenic macrophage subpopulations differed in their responses to rhM-CSF, suggesting that distinct mechanisms may be involved in their development and differentiation. The splenic red pulp macrophages present in unmanipulated op/op mice are an M-CSF-independent macrophage population. Although the marginal metallophilic macrophages and marginal zone macrophages are thought to be M-CSF-dependent, their development and differentiation appear to be influenced by locally produced M-CSF or other cytokines.
authors.affiliation: Second Department of Pathology, Kumamoto University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Umeda
authors.forename: L D
authors.initials: LD
authors.lastname: Shultz
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: S
authors.initials: S
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000473:pathology* / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000473:pathology; D010022:Osteopetrosis / Q000473:pathology* / Q000503:physiopathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000473:pathology* / Q000503:physiopathology
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor