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.
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
B C
BC
Gliniak
L R
LR
Rohrschneider
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D015151:Immunoblotting; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D011519:Proto-Oncogenes; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000235:genetics*; D013489:Suppression, Genetic
D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor