IL-4 and-5 prime human mast cells for different profiles of IgE-dependent cytokine production
IL-4 and-5 prime human mast cells for different profiles of IgE-dependent cytokine production
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DOI：
10.1073/pnas.180318697
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发表时间：
2000-09-12
影响因子：
11.1
通讯作者：
Boyce, JA
中科院分区：
文献类型：
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作者：
Ochi, H;De Jesus, NH;Boyce, JA
肥大细胞(MC)是一种依赖干细胞因子的组织造血细胞，具有显著的功能异质性。脐带血来源的人MC(HMC)表达IL-5的功能性受体，IL-5在体外介导干细胞因子依赖的HMC共生。虽然IL-5不是HMC正常发育所必需的，但我们认为它可能为HMC高亲和力的IgE(Fc Epsilon RI)受体(Fc Epsilon RI)依赖的细胞因子的产生而激活。正如之前针对IL-4所展示的那样。与仅由干细胞因子维持的HMC相比，IL-5诱导的HMC表达的稳态水平高2-4倍。IL-13、巨噬细胞炎性蛋白1α和粒细胞-巨噬细胞集落刺激因子在Fc epsilon RI交联后2小时转录，并分泌除IL-13外的2-5倍的相应细胞因子。6小时。与IL-4不同。IL-5对Fc-epsilon RI依赖的组胺释放无促进作用。因此。IL-5通过一种不同于IL-4的机制促进HMC产生细胞因子，并且产生不同的细胞因子。这些观察表明，IL-5对HMC具有潜在的自分泌作用，除了对嗜酸性粒细胞的旁分泌作用外，还可能对HMC的过敏免疫反应产生放大作用，并提示IL-4和IL-5都参与了HMC表型的调节。
Mast cells (MC) are stem cell factor-dependent tissue-based hematopoietic cells with substantial functional heterogeneity. Cord blood-derived human MC (hMC) express functional receptors for IL-5, and IL-5 mediates stem cell factor-dependent comitogenesis of hMC in vitro. Although IL-5 is not required for normal hMC development, we considered that it might prime hMC for their high-affinity Fc receptor for IgE (Fc epsilon RI)-dependent generation of cytokines. as previously demonstrated for IL-4. Compared with hMC maintained in stem cell factor alone, hMC primed with IL-5 expressed 2- to 4-fold higher steady-state levels of TNF-alpha, IL-5. IL-13, macrophage inflammatory protein 1 alpha, and granulocyte-macrophage colony-stimulating factor transcripts 2 h after Fc epsilon RI crosslinking and secreted 2- to 5-fold greater quantities of the corresponding cytokines, except IL-13. at 6 h. Unlike IL-4. IL-5 priming did not enhance Fc epsilon RI-dependent histamine release. Thus. IL-5 augments cytokine production by hMC by a mechanism distinct from that of IL-4 and with a different resultant profile of cytokine production. These observations suggest a potentially autocrine effect of IL-5 on hMC for amplification of allergic immune responses, in addition to its recognized paracrine effects on eosinophils, and implicate both IL-4 and IL-5 in the modulation of the hMC phenotype.