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O Kan, CM Heyworth, TM Dexter, PJ Maudsley, N Cook, SJ Vallance and AD Whetton
Department of Biochemistry and Applied Molecular Biology, UMIST,
Manchester, UK.
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.
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| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||