Colony-stimulating factor-1 impairs both proliferation and differentiation signals of erythropoietin during the commitment of bipotential NFS-60 cell line to the monocytic lineage.
The interleukin-3 (IL-3) dependent cell line NFS-60 contains bipotential progenitors that exhibit both erythroid and myelomonocytic potentials. In order to study their commitment to the monocytic lineage, NFS-60 cells were retrovirally transduced with mouse c-fms cDNA, which encodes the colony-stimulating factor-1 receptor (CSF-1R), resulting in the N-Fms cell line. N-Fms cells proliferated in response to CSF-1 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 was lost after a 24-hour cultivation in the presence of CSF-1 or, interestingly, both CSF-1 and IL-3. This loss of response to EPO was reverted following a brief passage (24 hours) in IL-3, but the rescued colonies did not undergo 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 potential in bipotential N-Fms cells by altering proliferative and differentiation signal of EPO.
Pawlak
G
G
Centre de Génétique Moléculaire et Cellulaire, Université Claude Bernard Lyon I, Villeurbanne, France.
Valadoux-Delplanque
C
C
Revol
V
V
Bourette
R P
RP
Blanchet
J P
JP
Mouchiroud
G
G
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage; D017931:DNA Primers; D004921:Erythropoietin / Q000378:metabolism / Q000494:pharmacology*; D016236:Genes, fms; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
D017931:DNA Primers; D011994:Recombinant Proteins; D004921:Erythropoietin; D016173:Macrophage Colony-Stimulating Factor