Interacting mast cells and eosinophils acquire an enhanced activation state in vitro
Interacting mast cells and eosinophils acquire an enhanced activation state in vitro
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DOI：
10.1111/all.12059
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发表时间：
2013-02-01
期刊：
影响因子：
12.4
通讯作者：
Levi-Schaffer, F.
中科院分区：
文献类型：
--
作者：
Elishmereni, M.;Bachelet, I.;Levi-Schaffer, F.
背景肥大细胞（MC）和嗜酸性粒细胞（Eos）是变态反应中的关键效应细胞，在变态反应性炎症的晚期和慢性阶段大量共定位。最近的证据已经概述了一个专门的过敏效应单位，其中MCs和EOS通过可溶性介质和物理接触进行通信。然而，这种双向串扰对细胞效应器活性的功能影响尚未被揭示。我们的目的是调查MC/嗜酸性粒细胞的相互作用是否可以影响这些细胞的即时和晚期活化表型。方法将人和小鼠MCs与Eos在不同条件下共培养12 h或13 d，并在选定的实验中阻断细胞-细胞接触。检测细胞迁移和介质释放，并应用流式细胞术对细胞内信号分子和表面受体进行染色。结果嗜酸性粒细胞通过涉及CD 482 B4相互作用的物理接触增强了基础MC介质释放并共同刺激了IgE激活的MC。相反，休息和IgE刺激的MCs导致嗜酸性粒细胞迁移和激活通过旁分泌依赖的机制。在长期共培养中观察到活化相关信号分子磷酸化增加和肿瘤坏死因子a释放增强。嗜酸性粒细胞也表现出增强的细胞间粘附分子1的表达，这取决于与MC的直接接触。结论：我们的研究结果揭示了MC/嗜酸性粒细胞相互作用的一个新的作用，在这两个细胞的增强短期和长期的激活，在一个组合的物理/旁分泌的方式。因此，这种增强的功能活性可能对过敏性疾病中炎症反应的持续存在起关键作用。
Background Mast cells (MCs) and eosinophils (Eos), the key effector cells in allergy, are abundantly co-localized particularly in the late and chronic stages of allergic inflammation. Recent evidence has outlined a specialized allergic effector unit in which MCs and Eos communicate via both soluble mediators and physical contact. However, the functional impact of this bi-directional crosstalk on the cells' effector activities has not yet been revealed. We aimed to investigate whether MC/eosinophil interactions can influence the immediate and late activation phenotypes of these cells. Methods Human and murine MCs and Eos were co-cultured under various conditions for 12 h or 13 days, and in selected experiments cellcell contact was blocked. Cell migration and mediator release were examined, and flow cytometry was applied to stain intracellular signaling molecules and surface receptors. Results Eosinophils enhanced basal MCs mediator release and co-stimulated IgE-activated MCs through physical contact involving CD482B4 interactions. Reciprocally, resting and IgE-stimulated MCs led to eosinophil migration and activation through a paracrine-dependent mechanism. Increased phosphorylation of activation-associated signaling molecules, and enhanced release of tumor necrosis factor a, was observed in long-term co-cultures. Eosinophils also showed enhanced expression of intercellular adhesion molecule 1, which depended on direct contact with MCs. Conclusions Our findings reveal a new role for MC/eosinophil interplay in augmenting short- and long-term activation in both cells, in a combined physical/paracrine manner. This enhanced functional activity may thus critically contribute to the perpetuation of the inflammatory response in allergic conditions.