GM-CSF in association with IL-1 triggers day-8 CFU-S into cell cycle: role of histamine.
Our recent evidence for the requirement of endogeneous histamine in IL-3-induced proliferation of day-8 CFU-S has prompted us to investigate whether or not GM-CSF, which shares with IL-3 the ability to stimulate bone marrow histamine synthesis, could also affect the cell cycle status of CFU-S via this mediator. We show herein that recombinant GM-CSF alone fails to trigger day-8 CFU-S into S phase, but supports their survival. However, in the same experimental conditions, GM-CSF in combination with IL-1 induces a CFU-S proliferation similar to that obtained in response to IL-3, while IL-1 by itself has no effect on this biological activity. We further provide evidence that this phenomenon is completely abolished: i) by preventing GM-CSF-induced histamine synthesis by alpha-FMH, the specific inhibitor of histidine decarboxylase (HDC), or ii) by blocking the binding sites of H2 histamine receptors with their specific antagonist oxmetidine. Similar results are obtained when progenitor-enriched bone marrow cells are used instead of the unfractionated population. In addition, we provide an argument in support of a histamine receptor modulation by GM-CSF that could explain the lack of effect of factor-induced histamine on day-8 CFU-S cell cycling. Indeed, the entry of these progenitors into S phase that is normally promoted by dimaprit, a specific histamine H2 receptor agonist, is abolished by a preincubation with GM-CSF. Taken together, our data support the conclusion that IL-1 makes CFU-S sensitive to GM-CSF-induced endogeneous histamine that will trigger them into cell cycle, while GM-CSF alone has no such effect on this biological activity.
Piquet-Pellorce
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INSERM U 25 - CNRS URA 122, Hôpital Necker, Paris, France.
Schneider
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E
Dy
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D000818:Animals; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D017259:Dimaprit; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006632:Histamine / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016196:S Phase / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D013890:Thiourea / Q000494:pharmacology
D007375:Interleukin-1; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013890:Thiourea; D017259:Dimaprit