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 mic e homozygous for osteopetrosis (op/op) mutation were studied. The muta nt mice are characterized by defective differentiation of osteoclasts, monocytes, and tissue macrophages due to the lack of functional macro phage 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 phago cytosis but the development of intracytoplasmic organelles and microvi llous projections was poor. After administration of CSF-1 daily for 2 weeks, macrophases in op/op mice developed lysosomes and microvillous projections. In the thymic medulla, T-cell zone of I;mph nodes, spleni c white pulp and epidermis of the op/op mice, the number of dendritic cells was similar to that in normal littermates and the dendritic cell s developed a tubulovesicular system typical of interdigitating cells. Birbeck granules in epidermal Langerhans cells were detected in unman ipulated op/op mice, op/op mice injected with CSF-1, and normal litter mates or control mice. However, in untreated op/op mice, dendritic cel ls projected shorter cytoplasmic processes than in normal littermates, normal control mice and CSF-1 injected op/op mice. These results indi cate that the differentiation and maturation of tissue macrophages are mediated by CSF-1, but the dendritic cell differentiation is controll ed by other factor(s) than CSF-1, most probably by GM-CSF.