Colony-stimulating factor-1 impairs both proliferation and differentiationsignals of erythropoietin during the commitment of bipotential NFS-60 cellline to the monocytic lineage

The interleukin-3 (IL-3) dependent cell line NFS-60 contains bipotential pr ogenitors that exhibit both erythroid and myelomonocytic potentials. In ord er to study their commitment to the monocytic lineage, NFS-60 cells were re trovirally transduced with mouse c-fms cDNA, which encodes the colony-stimu lating factor-1 receptor (CSF-1R), resulting in the N-Fms cell line. N-Fms cells proliferated in response to CSF-I with a growth rate similar to that obtained in response to IL-3 and progressively differentiated from myeloid blasts to monocytic cells within 3 days of culture. When maintained in IL-3 , about 3% of N-Fms cells formed large hemoglobinized colonies in semisolid cultures supplemented with erythropoietin (EPO), However, this property wa s lost after a 24-hour cultivation in the presence of CSF-I or, interesting ly, both CSF-I and IL-3, This loss of response to EPO was reverted followin g a brief passage (24 hours) in IL-3, but the rescued colonies did not unde rgo terminal erythrocytic differentiation. Furthermore, CSF-1 also affected proliferative response to EPO of N-Fms cells constitutively expressing EPO receptors, Our data strongly suggest that CSF-1 can suppress erythroid pot ential in bipotential N-Fms cells by altering proliferative and differentia tion signal of EPO, (C) 1999 International Society for Experimental Hematol ogy. Published by Elsevier Science Inc.