Expression of the M-CSF receptor is controlled posttranscriptionally by the dominant actions of GM-CSF or multi-CSF

We have isolated a murine myeloid precursor cell line (FDC-P1/MAC) that simultaneously expresses receptors for multi-CSF, GM-CSF, and M-CSF (c-fms protooncogene). FDC-P1/MAC cells express high levels of c-fms mRNA and protein when grown in M-CSF, whereas growth in multi-CSF or GM-CSF caused a dramatic reduction of c-fms glycoprotein and mRNA. Nuclear run-off assays demonstrated that c-fms transcription was not growth factor dependent and the regulation occurred posttranscriptionally. Factor switching experiments have shown that both multi-CSF and GM-CSF act dominantly and in a factor concentration dependent manner to suppress c-fms expression. In vitro agar assays of bone marrow cells grown in the presence of GM-CSF and M-CSF, individually and in combination, support the concept that GM-CSF can act dominantly to prevent monocyte/macrophage development. These results suggest that GM-CSF and multi-CSF can suppress development along the monocyte/macrophage lineage and offer a simple stochastic mechanism governing myeloid lineage restriction.