Piquet-Pellorce C, Dy M
CNRS URA 1461-Hôpital Necker-161, Paris, France.
Life Sci. 1991;48(25):2377-82. doi: 10.1016/0024-3205(91)90370-q.
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.
前列腺素E2(PGE2)可显著增强小鼠造血细胞对粒细胞-巨噬细胞集落刺激因子(GM-CSF)作出反应时的组胺合成。这种协同作用是由细胞内3':5'-环磷酸腺苷(cAMP)增加介导的,原因如下:(a)由福斯高林或异丁基甲基黄嘌呤产生的外源性和内源性cAMP可增强GM-CSF诱导的组胺合成;(b)PGE2和cAMP的最大增强作用并非累加的;(c)GM-CSF与PGE2共同作用可提高富含GM-CSF靶细胞的骨髓群体中的细胞内cAMP含量。cAMP和PGE2可增强GM-CSF诱导的组氨酸脱羧酶活性,表明这两种因子作用于组胺合成而非其释放。相反,白细胞介素3(IL-3)促进组胺合成(IL-3是唯一与GM-CSF具有此特性的细胞因子)不受PGE2或cAMP调节,提示造血细胞中诱导这种生物学活性存在两种不同机制。