Production of IL-5 and granulocyte-macrophage colony-stimulating factor by naive human mast cells activated by high-affinity IgE receptor ligation

Production of IL-5 and granulocyte-macrophage colony-stimulating factor by naive human mast cells activated by high-affinity IgE receptor ligation
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DOI:
10.1016/s0091-6749(97)70078-2
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发表时间:
1997-04-01
影响因子:
14.2
通讯作者:
Huston, DP
Huston, DP
中科院分区:
医学1区
文献类型:
--
作者:
Bressler, RB;Lesko, J;Huston, DP

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背景:晚期过敏反应是一种嗜酸性炎症反应,发生于过敏原暴露后数小时,可持续24小时,是变应性疾病的重要致病机制。目的:利用体外培养的人肥大细胞研究肥大细胞是否是促嗜酸性粒细胞细胞因子IL-5、IL-3和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的直接来源。方法:在干细胞因子作用下,从培养的骨髓单核细胞中获得人原始肥大细胞。采用半定量聚合酶链反应和酶联免疫吸附法分别检测培养肥大细胞对高亲和IgE受体连接的细胞因子信息和蛋白产量。结果:IL-5、IL-3和GM-CSF信使RNA在肥大细胞活化2小时内升高,IL-5和GM-CSF信使RNA在24小时内保持升高,而IL-3信使RNA迅速下降。IL-S和GM-CSF蛋白在刺激后4 ~ 6小时可测,分别在24小时和12小时达到峰值。未检出IL-3蛋白。结论:这些发现表明,幼稚肥大细胞不组成性地产生IL-5或GM-CSF蛋白,但它们是高亲和力IgE受体连接中嗜酸性细胞因子的主要来源。
Background: The late-phase allergic reaction is an eosinophilic inflammatory response that begins several hours after allergen exposure, may persist for 24 hours, and is an important pathogenic mechanism in allergic disease.Objective: Cultured naive human mast cells were used to investigate whether mast cells are a direct source of the eosinophil-promoting cytokines IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF).Methods: Naive human mast cells were derived from bone marrow mononuclear cells cultured in the presence of stem-cell factor. Cytokine message and protein production in response to high-affinity IgE receptor ligation of cultured mast cells were measured by semiquantitative polymerase chain reaction and ELISA, respectively.Results: IL-5, IL-3, and GM-CSF messenger RNA increased within 2 hours of mast cell activation, with IL-5 and GM-CSF message remaining elevated for 24 hours, whereas IL-3 mRNA rapidly declined. IL-S and GM-CSF protein were measurable 4 to 6 hours after stimulation and peaked by 24 and 12 hours, respectively. IL-3 protein was not detectable.Conclusion: These findings demonstrate that naive mast cells do not constitutively produce IL-5 or GM-CSF protein but are a major source of these eosinophilotropic cytokines on high-affinity IgE receptor Ligation.