Induced expression of c-fms in normal hematopoietic cells shows evidence for both conservation and lineage restriction of signal transduction in response to macrophage colony-stimulating factor.
Retrovirus-mediated gene transfer was used to obtain expression of the macrophage colony-stimulating factor (MCSF) receptor, c-fms, on hematopoietic lineages that normally do not express this receptor. Cultures of murine fetal liver cells infected with the c-fms retrovirus developed erythroid colonies in cultures stimulated with M-CSF. However, these colonies were fewer and less hemoglobinized than colonies in parallel cultures stimulated by erythropoietin. Culture of isolated clones demonstrated a direct action of M-CSF on erythroid clones. Culture of c-fms retrovirus-infected adult murine bone marrow cells showed megakaryocyte and novel macrophage-megakaryocyte clones when stimulated by M-CSF. Culture of isolated clones again confirmed a direct action of M-CSF on megakaryocyte clones. In contrast, M-CSF stimulation of c-fms-infected granulocytes and granulocyte progenitor cells did not elicit proliferation, enhanced survival, or functional stimulation of granulocytes. These findings provide evidence for both conservation and lineage restriction of signal transduction in normal hematopoietic cells.
McArthur
G A
GA
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Rohrschneider
L R
LR
Johnson
G R
GR
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D005333:Fetus; D005434:Flow Cytometry; D015870:Gene Expression; D016236:Genes, fms; D005822:Genetic Vectors; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection
D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor