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

Immunohistochemical techniques using an anti-mouse panmacrophage monoc lonal antibody anl anti-mouse monoclonal antibodies specific for margi nal metallophilic macrophages or marginal zone macrophages were used t o 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 t he normal littermates and the marginal metallophilic macrophages and m arginal zone macrophages were absent. After administration of recombin ant human macrophage colony-stimulating factor (rhM-CSF), numbers of r ed pulp macrophages increased rapidly, reaching levels found in normal littermates 1 week later. In contrast, the marginal metallophilic mac rophages as well as the marginal zone macrophages appeared slowly afte r rhM-CSF administration and their numbers were less than half of the baseline level of normal littermates even at 12 weeks of administratio n. The distribution of marginal metallophilic macrophages and marginal zone macrophages appearing after M-CSF administration was irregular i n the spleen of the op/op mice. These splenic macrophage subpopulation s differed in their responses to rhM-CSF, suggesting that distinct mec hanisms may be involved in their development and differentiation. The splenic red pulp macrophages present in unmanipulated op/op mice are a n M-CSF-independent macrophage population. Although the marginal metal lophilic macrophages and marginal zone macrophages are thought to be M -CSF-dependent, their development and differentiation appear to be inf luenced by locally produced M-CSF or other cytokines.