Ultrastructure of macrophages and dendritic cells in osteopetrosis (op) mutant mice lacking macrophage colony-stimulating factor (M-CSF/CSF-1) activity.
The ultrastructural features of macrophages and dendritic cells of mice homozygous for osteopetrosis (op/op) mutation were studied. The mutant mice are characterized by defective differentiation of osteoclasts, monocytes, and tissue macrophages due to the lack of functional macrophage colony stimulating factor (M-CSF/CSF-1) activity. In op/op mice, tissue macrophages were reduced in number and smaller than in normal littermates. Macrophages in op/op mice showed various degrees of phagocytosis but the development of intracytoplasmic organelles and microvillous projections was poor. After administration of CSF-1 daily for 2 weeks, macrophages in op/op mice developed lysosomes and microvillous projections. In the thymic medulla, T-cell zone of lymph nodes, splenic white pulp and epidermis of the op/op mice, the number of dendritic cells was similar to that in normal littermates and the dendritic cells developed a tubulovesicular system typical of interdigitating cells. Birbeck granules in epidermal Langerhans cells were detected in unmanipulated op/op mice, op/op mice injected with CSF-1, and normal littermates or control mice. However, in untreated op/op mice, dendritic cells projected shorter cytoplasmic processes than in normal littermates, normal control mice and CSF-1 injected op/op mice. These results indicate that the differentiation and maturation of tissue macrophages are mediated by CSF-1, but the dendritic cell differentiation is controlled by other factor(s) than CSF-1, most probably by GM-CSF.
Usuda
H
H
Second Department of Pathology, Niigata University School of Medicine, Japan.
Naito
M
M
Umeda
S
S
Takahashi
K
K
Shultz
L D
LD
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000648:ultrastructure*; D005260:Female; D006720:Homozygote; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D010022:Osteopetrosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor