Synergistic suppression: anomalous inhibition of the proliferation of factor-dependent hemopoietic cells by combination of two colony-stimulating factors.
Cells of the continuous murine hemopoietic cell line FDC-P1 expressing macrophage-colony-stimulating factor (M-CSF) receptors following retroviral insertion of murine c-fms cDNA proliferated clonally when stimulated by granulocyte/macrophage (GM)-CSF, multipotential CSF, or M-CSF. However, M-CSF combined with either GM-CSF or multi-CSF, even at low CSF concentrations, strongly inhibited colony formation, with loss of clonogenicity in affected cells accompanied by increased macrophage differentiation. Stimulation by these CSF combinations did not induce short-term changes in CSF receptor expression or internalization. FDC-P1 cells expressing another inserted tyrosine kinase receptor, basic fibroblast growth factor receptor, did not exhibit suppression when GM-CSF was combined with fibroblast growth factor. This phenomenon of synergistic suppression may have relevance for the future clinical use of combinations of CSFs, because a potentially similar suppression is also observable with some normal macrophage progenitor cells.
Metcalf
D
D
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Nicola
N A
NA
Gough
N M
NM
Elliott
M
M
McArthur
G
G
Li
M
M
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004705:Endocytosis; D037502:Galectin 3; D015870:Gene Expression; D016236:Genes, fms; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000008:administration & dosage*; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism
D000943:Antigens, Differentiation; D037502:Galectin 3; D007377:Interleukin-3; D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor