Structure, biosynthesis and biological roles of monocyte-macrophage colony stimulating factor (CSF-1 or M-CSF)

Abstract

CSF-1 or M-CSF is a homodimeric glycosylated protein purified to homogeneity through its hematopoietic growth factor properties. It has recently been cloned and sequenced as a unique gene encoding several m-RNAs and peptidic species. Its receptor has been identified as the c-fms protooncogene product expressed at the surface of all CSF-1 responsive cells as a transmembrane tyrosine kinase responsible for CSF-1 induced signal transduction. CSF-1 is permanently present in serum and several biological fluids at stable concentrations and can thus be considered as a hormone. In vivo concentrations are mainly regulated by binding, internalization and degradation of the CSF-1 molecule by hepatic and splenic macrophage receptors. Very little is known about the organs and cell types responsible for in vivo CSF-1 synthesis. In vitro, CSF-1 regulates the survival, proliferation and differentiation of the monocyte-macrophage lineage from progenitors to mature cells and activates several important functions of mature tissular macrophages. Recent results obtained with injections of recombinant CSF-1 show that interesting activities, e.g., as ADCC, NK or antiinfectious effects, that had been initially observed in vitro can also be induced in vivo. All these in vitro and in vivo data and the recent availability of large amounts of pure recombinant human CSF-1 point to the diagnostic value of CSF-1 concentration measurements in biological fluids and suggest a therapeutic role for CSF-1 infusion in cancer and infection therapy.