New role for histamine in interleukin-3-induced proliferation of hematopoietic stem cells.
This study investigated the effect of histamine generated by murine bone marrow cells in response to IL-3 on one particular biological activity of this growth factor, i.e., triggering of cells forming colonies in spleen (CFU-S) into S phase. Evidence is provided that i) IL-3-induced day-8 CFU-S cell cycling, evaluated by hydroxy-urea suicide, is completely abrogated when the binding of histamine to its H2 receptors is blocked by the specific antagonist oxmetidine, whereas cetirizine, a H1 receptor antagonist, is ineffective; and ii) the entry of day-8 CFU-S into S phase in response to IL-3 is likewise abolished when the histamine synthesis promoted by the growth factor is prevented by alpha-fluoromethylhistidine, a specific inhibitor of the histamine-forming enzyme, histidine decarboxylase. Similar results are obtained with both drugs, when a progenitor-enriched bone marrow population is used instead of total cells. Furthermore, i.v. injection of recombinant (r)IL-3 results within 2 hr in a substantial increase in bone marrow cell histamine synthesis together with triggering of day-8 CFU-S into cycle, the latter being completely abolished by a simultaneous injection of the H2 histamine receptor antagonist oxmetidine. Thus, our findings support the notion that both in vitro and in vivo the proliferation of early CFU-S in response to IL-3 is modulated by histamine via its H2 receptors. This conclusion is also consistent with the observation that dimaprit, a specific agonist of these receptors not only enhances the sensitivity of day-8 CFU-S to HU after a 2 hr incubation with bone marrow cells but also increases, to the same extent as IL-3, the number of colonies formed in irradiated spleens after a 5 hr pretreatment.
Schneider
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E
INSERM U25-CNRS UA 122 Hôpital Necker, Paris, France.
Piquet-Pellorce
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C
Dy
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M
D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects*; D017332:Cetirizine; D003114:Colony-Forming Units Assay; D017259:Dimaprit; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006632:Histamine / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006919:Hydroxyzine / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology*; D008762:Methylhistidines / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D013890:Thiourea / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D007377:Interleukin-3; D008762:Methylhistidines; D006919:Hydroxyzine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D013890:Thiourea; D017332:Cetirizine; C027703:oxmetidine; D017259:Dimaprit