CSF-1 and interferon-gamma act synergistically to promote differentiation of FDC-P1 cells into macrophages.
FDC-P1 cells expressing the wildtype CSF-1 receptor, FDwtfms, differentiate into macrophages during incubation with CSF-1. This response is amplified in the presence of interferon-gamma. Cells expressing the 807F mutant receptor, 807F cells, proliferate in response to CSF-1 and do not differentiate. However, in response to CSF-1 and interferon-gamma they differentiate as well. CSF-1 causes the activation of STAT proteins in FDwtfms cells, but not in 807F cells. Cellular differentiation correlates with a sustained activation of STAT1 and STAT3 in response to interferon-gamma over at least 40 hours. However, interferon-gamma alone did not cause differentiation of cells expressing either receptor. Other defects in response to CSF-1 of the 807F cells, such as lack of PLC gamma 2 activation, were not complemented by co-incubation of the cells with CSF-1 and interferon-gamma. It appears that a combination of signaling pathways are activated by CSF-1 and interferon-gamma which caused the shift of response from proliferation to differentiation in the 807F cells and an enhanced differentiation in the FDwtfms cells.
Novak
U
U
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia. ulrike_novak.rmh_facmed@muwaye.unimelb.edu.au
Nicholson
S
S
Bourette
R P
RP
Rohrschneider
L R
LR
Alexander
W
W
Paradiso
L
L
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D016297:Mutagenesis, Site-Directed; D051966:Phospholipase C gamma; D010766:Phosphorylation; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D007527:Isoenzymes; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016186:Receptor, Macrophage Colony-Stimulating Factor; D010738:Type C Phospholipases; D051966:Phospholipase C gamma