CSF-1

Colony-stimulating factor 1 (CSF-1) is the primary regulator of the survival, proliferation, and differentiation of mononuclear phagocytes and also regulates cells of the female reproductive tract. Produced by a wide variety of cell types, CSF-1 acts humorally and locally. It is secreted into the circulation as a glycoprotein or chondroitin sulfate-containing proteoglycan and expressed on the surface of CSF-1-producing cells. CSF-1 effects are mediated by the CSF-1 receptor tyrosine kinase that is encoded by the c-fms protooncogene product. Osteopetrotic Csf1op/Csf1op mice possess an inactivating mutation in the CSF-1 gene and besides striking reductions in numbers of osteoclasts and certain tissue macrophages, they exhibit a pleiotropic phenotype. This pleiotropic phenotype may be due to trophic and/or scavenger actions of macrophages and other cell types regulated by CSF-1, that control such characteristics as dermal thickness, male and female fertility, and neural processing. CSF-1 appears to play an autocrine and/or paracrine role in cancers of the female reproductive tract and the myeloid system.