支气管上皮和嗜碱性粒细胞的IL-17A活化：一个新的炎症机制
2010/08/20
嗜碱性粒细胞是Th2细胞的诱导辅助细胞以及IgE介导慢性变应性炎症的启动因子。因此在变应性炎症部位，如过敏性哮喘患者的气道，集聚了大量的嗜碱性粒细胞和气道上皮细胞（Th17）。
为了进一步阐明哮喘气道炎症机制，Wong等对原代人嗜碱性粒细胞、KU812传代嗜碱性粒细胞以及原代人气道上皮细胞和EBAS-2B传代上皮细胞上IL-17A的活化情况进行观测。研究采用ELISA和流式细胞仪技术分析细胞因子、趋化因子、粘附分子和细胞间细胞分子。
经过共同培养，气道上皮细胞和嗜碱性粒细胞内，上皮细胞炎症因子——IL-6以及趋化因子——CCL-2的释放明显增加。后者能趋化嗜碱性粒细胞、嗜酸性粒细胞和单核细胞向炎症部分集聚。这种促进作用可被IL-17A所增强，而且上皮细胞和嗜碱性粒细胞之间的直接作用有赖于IL-17A诱导的IL-6和CCL2。在两种细胞相互作用中，气道上皮细胞表面的细胞间粘附分子-1（ICAM-1）上调。嗜碱性粒细胞和支气管上皮细胞在IL-17A刺激下的相互作用还受细胞外信号调节激酶（ERK）的调节，后者包括c-JunN末端蛋白激酶、p38-MAPK和核因子κB等途径。
本研究揭示了气道上皮细胞和嗜碱性粒细胞在过敏性哮喘中的一种新型免疫病理作用，即二者相互作用可直接激活粒细胞介导的炎症反应。这些研究结果对于更好的掌握哮喘发病的炎症机制具有重要意义。
（韩伟 青岛大学附属青岛市立医院东院 266071 摘译）
（Eur Respir J 2010; 35:883-893）
Interleukin-17A activation on bronchial epithelium and basophils: a novel inflammatory mechanism
C. K. Wong1,4, J. Cao1,4, Y. B. Yin2 and C. W. K. Lam1,3 Dept of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Basophils are the accessory cell type for T-helper (Th)2 induction and initiators in immunoglobulin E-mediated chronic allergic inflammation. Basophils and Th17 cells accumulate at the inflammatory sites, such as the airways of allergic asthmatic patients.
We investigated the activation of interleukin (IL)-17A on the primary human basophils/KU812 basophilic cells and primary human bronchial epithelial cells/BEAS-2B bronchial epithelial cells. Cytokines, chemokines, adhesion molecules and intracellular signalling molecules were assayed by ELISA or flow cytometry.
Co-culture of bronchial epithelial cells and basophils could significantly induce the release of IL-6, an epithelial inflammatory cytokine, and CCL2, a chemokine for basophils, esosinophils and monocytes. Such induction was synergistically enhanced by IL-17A, and direct interaction between these two cells was necessary for IL-17A-induced IL-6 and CCL2 release. Surface expression of intercellular adhesion molecule-1 on bronchial epithelial cells was also upregulated upon their interaction. The interaction of basophils and bronchial epithelial cells under IL-17A stimulation was differentially regulated by extracellular signal-regulated kinase, c-Jun N-terminal protein kinase, p38 mitogen-activated protein kinase and nuclear factor-B pathways.
These findings suggest a novel immunopathological role of Th17 cells and basophils in allergic asthma through the activation of granulocyte-mediated inflammation initiated by the direct interaction between basophils and bronchial epithelial cells.
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