CSF-1 and Interferon-γ Act Synergistically to Promote Differentiation of FDC-P1 Cells into Macrophages

Abstract

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-γ. 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-γ 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-γ over at least 40 hours. However, interferon-γ 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 PLCγ2 activation, were not complemented by co-incubation of the cells with CSF-1 and interferon-γ. It appears that a combination of signaling pathways are activated by CSF-1 and interferon-γ which caused the shift of response from proliferation to differentiation in the 807F cells and an enhanced differentiation in the FDwtfms cells.

Key Words:

• CSF-1
• interferon-γ
• STAT proteins
• differentiation