Cytokine regulation of the macrophage (M phi) system studied using the colony stimulating factor-1-deficient op/op mouse.
The macrophage (M phi) lineage is more complex than other myeloid lineages of hematopoietic cells and includes strikingly different end cells such as Kupffer cells, alveolar M phi, histiocytes, serosal M phi, synovial type A cells, microglia, osteoclasts, and possibly dendritic cells. These cells are formed under the influence of primary M phi growth factors such as colony stimulating factor (CSF)-1, granulocyte-M phi (GM)-CSF, and interleukin-3. The dissection of the system has been greatly facilitated by discovery of the osteopetrotic op/op mouse, which has a spontaneous knockout of the gene for CSF-1 and possesses generalized but differential deficiency of various local subpopulations of M phi. Studies using this model indicate that the M phi lineage is split into CSF-1-dependent and CSF-1-independent cells that are largely independently regulated. These contribute variably to different local populations and have largely, but not totally, overlapping functions. Both CSF-1 and GM-CSF are responsible for transition of cells of the M phi lineage from bone marrow to blood, and from blood to tissues, and have a critical extramedullary role. Regulation of the M phi system by CSF-1 is complex, with some local populations dependent on circulating CSF-1 and some supported exclusively by locally produced CSF-1. Colony stimulating factor-1-dependent M phi are not required for the generation of a specific immune response. Instead, most likely they play a regulatory role in various tissue reactions including responses to bacterial infection, neoplasia, and atherosclerosis. A hypothetical major role of CSF-1-independent M phi is to collaborate with lymphocytes in mounting an immune response. These issues need further exploration using animals with knockouts of genes for other M phi growth and activation factors and their receptors.
Wiktor-Jedrzejczak
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Department of Immunology, Military School of Medicine, Warsaw, Poland.
Gordon
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D000818:Animals; D019070:Cell Lineage; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D010022:Osteopetrosis / Q000378:metabolism
D016173:Macrophage Colony-Stimulating Factor