Prostaglandin E2 potentiates granulocyte-macrophage colony stimulating factor-induced histamine synthesis in bone marrow cells: role of cAMP.
Histamine synthesis in response to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) by murine hematopoietic cells is strikingly potentiated by prostaglandin E2 (PGE2). This synergy is mediated by an increase in intracellular adenosine 3':5'-cyclic monophosphate (cAMP), since: (a) exogeneous and endogeneous cAMP generated either by forskolin or IBMX potentiate GM-CSF-induced histamine synthesis, (b) the maximal potentiating effects of PGE2 and cAMP are not cumulative, and (c) GM-CSF together with PGE2 enhances intracellular cAMP content in a bone marrow population enriched for GM-CSF target cells. cAMP and PGE2 enhance histidine decarboxylase activity induced by GM-CSF showing that both factors act on histamine synthesis rather than on its release. Conversely, histamine synthesis promoted by Interleukin 3 (IL-3), the unique cytokine sharing this property with GM-CSF, is not modulated by PGE2 or cAMP, suggesting two distinct mechanisms for the induction of this biological activity in hematopoietic cells.
Piquet-Pellorce
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CNRS URA 1461-Hôpital Necker-161, Paris, France.
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D000818:Animals; D001853:Bone Marrow / Q000201:enzymology*; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology*; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006632:Histamine / Q000096:biosynthesis*; D006640:Histidine Decarboxylase / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL
D007377:Interleukin-3; D003994:Bucladesine; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000242:Cyclic AMP; D006640:Histidine Decarboxylase; D015232:Dinoprostone