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 infection of FDCP-mix cells with a retroviral vector expressing the granulocyte-macrophage colony-stimulating factor (CSF) gene, proliferates continuously in interleukin 3 and presents the unique advantage of synchronous granulocyte and macrophage differentiation upon interleukin 3 withdrawal. Using this system, we showed previously that the mRNAs for lineage-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 specific question of the regulation of the expression of CSF-1 and its receptor and of their relevance to macrophage differentiation. Both genes were transcribed with equal efficiency in undifferentiated and differentiating cells. CSF-1 mRNA was detected in undifferentiated cells and increased slightly in the early phases of differentiation. CSF-1 receptor mRNA, absent in undifferentiated cells, accumulated early in differentiation (24 h) and remained constant thereafter. The production of both proteins, detected later during the differentiation of A4GMV#2 cells and of bone marrow-derived myeloid precursors, was therefore controlled at the posttranscriptional level. CSF-1 was produced by cells of the macrophage lineage and accumulated in mature phagocytes. A neutralizing anti-CSF-1 serum selectively impaired macrophage differentiation of A4GMV#2 cells and, most significantly, of primary myeloid precursors. These data indicate that CSF-1 and its receptor interact productively during differentiation and that the resulting autocrine stimulation selectively promotes macrophage maturation.
Heusohn
F
F
Department of Immunobiology, Fraunhofer Institute for Toxicology and Molecular Biology, Hannover, Federal Republic of Germany.
Pohler
U
U
Decker
T
T
Just
U
U
Ostertag
W
W
Lohmann-Matthes
M L
ML
Baccarini
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D012323:RNA Processing, Post-Transcriptional; D016184:Receptors, Colony-Stimulating Factor / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*
D016184:Receptors, Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor