Activation and proliferation signals in murine macrophages: synergistic interactions between the hematopoietic growth factors and with phorbol ester for DNA synthesis.
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.
D000818:Animals; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D004731:Endotoxins / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D004731:Endotoxins; D006133:Growth Substances; D007377:Interleukin-3; D008070:Lipopolysaccharides; D010703:Phorbol Esters; D003208:Concanavalin A; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA