GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR CORRECTS MACROPHAGE DEFICIENCIES, BUT NOT OSTEOPETROSIS, IN THE COLONY-STIMULATING FACTOR-1-DEFICIENT OP OP MOUSE/

The op mutation in the mouse is in the coding region of the colony-sti mulating factor-1 (CSF-1) gene, prevents formation of biologically act ive factor, and, thus, results in generalized macrophage deficiency an d, in osteopetrosis, secondary to deficiency of osteoclasts. Although a few macrophages and osteoclasts are present in these mutants, it was not clear whether the inability of endogenous granulocyte-macrophage CSF (GM-CSF) to compensate for the absence of CSF-1 was due to the lim itations of biological activity of this molecule or to its inability t o reach respective target populations. In this study, we examined whet her sc GM-CSF in large doses (20-40 mug/mouse . day) for 3 weeks would correct some or all of the deficiencies observed in mutant mice. All organ macrophage populations tested (liver, spleen, thymus, marrow, pl eural, and peritoneal cavity) were significantly increased, reaching l evels exceeding those observed in normal mice. Restoration of peritone al and pleural macrophage populations by sc GM-CSF is of particular in terest, because it was not previously observed in op/op mice treated w ith sc CSF-1. In contrast, there was no indication of increased bone r esorption, no appearance of osteoclasts, and no tooth eruption in resp onse to GM-CSF treatment. These data suggest that GM-CSF is able to co mpensate for the absence of CSF-1 during macrophage formation, but is unable to play a similar role in osteoclast differentiation.