In vivo role of macrophage growth factors as delineated using CSF-1 deficient op/op mouse.
Total absence of CSF-1 in the op/op mouse leads to a profound and generalized deficiency of macrophages and to osteopetrosis subsequent to the absence of osteoclasts. These observations confirm that CSF-1 is a genuine regulator of macrophage and osteoclast formation in vivo. Further studies in affected animals have shown that the CSF-1 absence variably affects macrophage differentiation stages and different organ macrophage populations, and that functionally competent macrophages are produced in low numbers without CSF-1, presumably under the influence of GM-CSF and IL-3. The op/op mice have increased levels of both endogenous GM-CSF and IL-3, which apparently are not fully able to compensate for the absence of CSF-1. Macrophage deficiencies but not osteoclast deficiencies in the op/op mouse could be completely corrected by exogenous GM-CSF, while exogenous CSF-1 corrects both osteoclast and macrophage deficiencies, but only in those tissues which could be reached by CSF-1 from the circulation. Despite severe quantitative macrophage deficiencies, the op/op mice demonstrate normal in vivo phagocytosis and immune functions suggesting that CSF-1 dependent macrophages do not contribute significantly to those processes in vivo. On the other hand, the op/op mice demonstrate severe secondary deficiencies of TNF-alpha, IL-1 alpha, and G-CSF suggesting that major function of CSF-1 dependent macrophages is the release of monokines.
Wiktor-Jedrzejczak
W
W
Department of Immunology, Central Clinical Hospital, Military School of Medicine, Warsaw, Poland.
D000818:Animals; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D007377:Interleukin-3 / Q000378:metabolism / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010022:Osteopetrosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000628:therapy
D007377:Interleukin-3; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor