Extracellular vesicles, especially derived from Gram-negative bacteria, in indoor dust induce neutrophilic pulmonary inflammation associated with both Th1 and Th17 cell responses
Extracellular vesicles, especially derived from Gram-negative bacteria, in indoor dust induce neutrophilic pulmonary inflammation associated with both Th1 and Th17 cell responses
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DOI：
10.1111/cea.12085
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发表时间：
2013-04-01
影响因子：
6.1
通讯作者：
Kim, Y. -K.
中科院分区：
文献类型：
--
作者：
Kim, Y. -S.;Choi, E. -J.;Kim, Y. -K.
背景室内粉尘中的许多细菌成分可引起炎症性肺部疾病。细菌会将纳米级的囊泡分泌到细胞外环境中，但室内粉尘中的细菌来源的胞外囊泡是否与炎症性肺部疾病有关，仍有待确定。目的探讨室内空气中细胞外小泡(EV)与肺部炎症和/或哮喘发病机制的关系。方法对某公寓床垫进行室内粉尘采集。采用序贯超滤和超速离心法制备EV。在EV暴露于呼吸道后，评估先天和获得性免疫反应。结果反复鼻腔应用室内粉尘所致的中性粒细胞肺部炎症，并伴有Th1、Th17细胞的肺内浸润。EV直径为50200 nm，室内粉尘蛋白质浓度为102.5g/g。这些小泡被呼吸道上皮细胞和肺泡巨噬细胞内化，这一过程可被多粘菌素B(革兰氏阴性菌外膜成分脂多糖的拮抗剂)阻断。鼻腔注射0.1或1g这些囊泡4周，可引起中性粒细胞肺部炎症。这种表型伴随着Th1和Th17细胞的肺浸润，多粘菌素B可以逆转这种情况。特应性哮喘儿童的血清EV反应性IgG1水平显著高于特应性健康儿童和鼻炎或皮炎儿童。结论&临床意义室内粉尘EV，尤其是革兰氏阴性菌，可能是中性粒细胞呼吸道疾病的病原体。
Background Many bacterial components in indoor dust can evoke inflammatory pulmonary diseases. Bacteria secrete nanometre-sized vesicles into the extracellular milieu, but it remains to be determined whether bacteria-derived extracellular vesicles in indoor dust are pathophysiologically related to inflammatory pulmonary diseases. Objective To evaluate whether extracellular vesicles (EV) in indoor air are related to the pathogenesis of pulmonary inflammation and/or asthma. Methods Indoor dust was collected from a bed mattress in an apartment. EV were prepared by sequential ultrafiltration and ultracentrifugation. Innate and adaptive immune responses were evaluated after airway exposure of EV. Results Repeated intranasal application of indoor-dust-induced neutrophilic pulmonary inflammation accompanied by lung infiltration of both Th1 and Th17 cells. EV 50200nm in diameter were present (102.5g protein concentration/g dust) in indoor dust. These vesicles were internalized by airway epithelial cells and alveolar macrophages, and this process was blocked by treatment of polymyxin B (an antagonist of lipopolysaccharide, an outer-membrane component of Gram-negative bacteria). Intranasal application of 0.1 or 1g of these vesicles for 4weeks elicited neutrophilic pulmonary inflammation. This phenotype was accompanied by lung infiltration of both Th1 and Th17 cells, which were reversed by treatment of polymyxin B. Serum dust EV-reactive IgG1 levels were significantly higher in atopic children with asthma than in atopic healthy children and those with rhinitis or dermatitis. Conclusion & Clinical Relevance Indoor dust EV, especially derived from Gram-negative bacteria, is a possible causative agent of neutrophilic airway diseases.