COORDINATE EXPRESSION OF THE LINEAGE-SPECIFIC GROWTH-FACTOR COLONY-STIMULATING FACTOR (CSF)-1 AND ITS RECEPTOR SELECTIVELY PROMOTES MACROPHAGE MATURATION DURING DIFFERENTIATION OF MULTIPOTENTIAL PROGENITOR CELLS

The multipotent hematopoietic precursor line A4GMV#2, derived by infec tion of FDCP-mix cells with a retroviral vector expressing the granulo cyte-macrophage colony-stimulating factor (CSF) gene, proliferates con tinuously in interleukin 3 and presents the unique advantage of synchr onous granulocyte and macrophage differentiation upon interleukin 3 wi thdrawal. Using this system, we showed previously that the mRNAs for l ineage-specific receptors (granulocyte-CSF receptors, CSF-1 receptors, and Erythropoietin receptors) and ligands (granulocyte-CSF and CSF-1) are up-regulated during myeloid maturation. Here we address the speci fic question of the regulation of the expression of CSF-1 and its rece ptor and of their relevance to macrophage differentiation. Both genes were transcribed with equal efficiency in undifferentiated and differe ntiating cells. CSF-1 mRNA was detected in undifferentiated cells and increased slightly in the early phases of differentiation. CSF-1 recep tor mRNA, absent in undifferentiated cells, accumulated early in diffe rentiation (24 h) and remained constant thereafter. The production of both proteins, detected later during the differentiation of A4GMV#2 ce lls and of bone marrow-derived myeloid precursors, was therefore contr olled at the posttranscriptional level. CSF-1 was produced by cells of the macrophage lineage and accumulated in mature phagocytes. A neutra lizing anti-CSF-1 serum Selectively impaired macrophage differentiatio n of A4GMV#2 cells and, most significantly, of primary myeloid precurs ors, these data indicate that CSF-1 and its receptor interact producti vely during differentiation and that the resulting autocrine stimulati on selectively promotes macrophage maturation.