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JA Hamilton, G Vairo, NA Nicola, A Burgess, D Metcalf and SR Lingelbach
University of Melbourne, Department of Medicine, Royal Melbourne Hospital,
Parkville, Australia.
There has been recent interest in the synergistic interactions between the
growth factors involved in the in vitro control of hematopoiesis and other
cell lineages. As a convenient model system, such interactions governing
the DNA synthesis in murine bone marrow-derived macrophages (BMMs) were
studied. By themselves, murine colony- stimulating factor-1 (CSF-1) and
recombinant murine granulocyte- macrophage CSF (GM-CSF) were stimulators of
DNA synthesis in quiescent or noncycling BMMs, whereas recombinant murine
interleukin-3 (IL-3) and the phorbol ester,
12-O-tetradecanoyl-phorbol-13-acetate (TPA), were weak mitogens. On the
other hand, murine granulocyte CSF (G-CSF), concanavalin A (Con A), and
lipopolysaccharide (LPS) were inactive on their own. When the quiescent
BMMs were exposed to combinations of the CSFs, there were striking
synergistic effects for both GM-CSF and IL-3 with suboptimal doses of
CSF-1, with a smaller effect for GM-CSF with IL-3 and little or no effect
for CSF-1 with G-CSF. CSF-1, GM-CSF, and IL-3 could also synergize with
TPA; CSF-1 cooperated with 1-oleoyl-2- acetylglycerol (OAG), both sets of
results pointing to an interaction with protein kinase C. LPS completely
abolished the CSF-1-mediated stimulation of DNA synthesis. We propose that
BMMs are suitable normal cells in which to examine in depth the various
mechanistic possibilities for these interactions.
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