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 populations by sc GM-CSF is of particular interest, because it was not previously observed in op/op mice treated with sc CSF-1. In contrast, there was no indication of increased bone resorption, no appearance of osteoclasts, and no tooth eruption in response to GM-CSF treatment. These data suggest that GM-CSF is able to compensate for the absence of CSF-1 during macrophage formation, but is unable to play a similar role in osteoclast differentiation.
Wiktor-Jedrzejczak
W
W
Department of Immunology, Central Clinical Hospital, Military School of Medicine, Warsaw, Poland.
Urbanowska
E
E
Szperl
M
M
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000172:deficiency*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D010022:Osteopetrosis / Q000473:pathology*; D010994:Pleura / Q000473:pathology; D011994:Recombinant Proteins
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor