Interferon-gamma stimulates the survival and influences the development of bipotential granulocyte-macrophage colony-forming cells.
The effects of interferon-gamma (IFN-gamma) on a highly enriched population of granulocyte-macrophage colony-forming cells (GM-CFC) were assessed. When added with myeloid growth factors (interleukin-3 [IL-3], granulocyte-macrophage colony-stimulating factor [GM-CSF], or macrophage-CSF [M-CSF]), IFN-gamma inhibited the formation of colonies in soft agar assays. Furthermore IFN-gamma stimulated an increase in the number of macrophages present in colonies formed in the presence of IL-3. IFN-gamma also inhibited M-CSF-, GM-CSF-, or IL-3-stimulated [3H]-thymidine incorporation in highly enriched GM-CFC. However, when added in the absence of hematopoietic growth factors, IFN-gamma promoted the survival of GM-CFC and had a modest stimulatory effect on DNA synthesis. The direct interaction of the IFN with GM-CFC was confirmed by showing its ability to rapidly activate the sodium/hydrogen antiport in GM-CFC, as do the mitogens GM-CSF, M-CSF, and IL-3. However, the effect of IFN-gamma on intracellular pH and DNA synthesis was transient and pretreatment with IFN markedly inhibited the ability of GM-CSF, M-CSF, and IL-3 to activate the sodium/hydrogen antiport. IFN-gamma has a dual effect on GM-CFC, decreasing the rate of cell death but also limiting the proliferative response to CSFs.
Kan
O
O
Department of Biochemistry and Applied Molecular Biology, UMIST, Manchester, UK.
Heyworth
C M
CM
Dexter
T M
TM
Maudsley
P J
PJ
Cook
N
N
Vallance
S J
SJ
Whetton
A D
AD
D000818:Animals; D001854:Bone Marrow Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007371:Interferon-gamma / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D006133:Growth Substances; D007377:Interleukin-3; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor