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-stimulating factor-1 (CSF-1) gene, prevents formation of biologically active factor, and, thus, results in generalized macrophage deficiency and, 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 limitations of biological activity of this molecule or to its inability to reach respective target populations. In this study, we examined whether sc GM-CSF in large doses (20-40 micrograms/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, pleural, and peritoneal cavity) were significantly increased, reaching levels exceeding those observed in normal mice. Restoration of peritoneal and pleural macrophage populatio...