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, differen tiate into macrophages during incubation with CSF-1. This response is amplified in the presence of interferon-gamma. Cells expressing the 80 7F mutant receptor, 807F cells, proliferate in response to CSF-1 and d o not differentiate. However, in response to CSF-1 and interferon-gamm a they differentiate as well. CSF-1 causes the activation of STAT prot eins 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 recept or. 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 combinati on of signaling pathways are activated by CSF-1 and interferon-gamma w hich caused the shift of response from proliferation to differentiatio n in the 807F cells and an enhanced differentiation in the FDwtfms cel ls.