The biology and action of colony stimulating factor-1

Colony stimulating factor 1 (CSF-1) is a growth factor for mononuclear phagocytic cells. Through alternative mRNA splicing and differential post-translational proteolytic processing, CSF-1 can either be secreted into the circulation as a glycoprotein or chondroitin sulfate-containing proteoglycan or expressed as a membrane-spanning glycoprotein on the surface of synthesizing cells. The discovery that the osteopetrotic (op/op) mutant mouse possesses an inactivating mutation in the CSF-1 gene has greatly contributed to our understanding of CSF-1 biology. CSF-1 directly regulates some non-mononuclear phagocytic cells that express the CSF-1 receptor tyrosine kinase, but is not required for their development. However, it directly regulates the development and maintenance of tissue macrophage subpopulations that appear to have important trophic and/or scavenger roles in tissue morphogenesis and function. Depending on the tissue, this regulation may be local (via the cell-surface form) localized (via the sequestered proteoglycan form) or humoral. It appears that the CSF-1 dependent tissue macrophage subpopulations, via their effects on other cell types, can significantly affect functions in tissues as diverse as testis, brain and skin, and their absence in op/op mice may explain the pleiotropy of the op/op phenotype. To investigate post-CSF-1 receptor signaling in the macrophage, procedures have been developed for the purification and sequence determination of the proteins that are rapidly phosphorylated on tyrosine in response to CSF-1. Several have been identified and the behavior of one of them, protein tyrosine phosphatase 1C (PTP1C), is discussed.