CSF-1 and interferon-γ 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.