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经鼻腔接种悬浮颗粒物引起 NC/Nga 小鼠的气道炎症反应。

Inflammatory airway responses by nasal inoculation of suspended particulate matter in NC/Nga mice.

机构信息

Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, Japan.

出版信息

Environ Toxicol. 2014 Jun;29(6):642-54. doi: 10.1002/tox.21791. Epub 2012 Jul 10.

Abstract

To evaluate the allergic effect of airborne particulate matter (PM) on the airway, separated soluble supernatant (Sup) and insoluble precipitate (Pre) in suspended PM were inoculated into NC/Nga mice with a high sensitivity for mite allergens. Sup, Pre, or both Sup and Pre with or without pronase treatment were inoculated via the nasal route five times for sensitization and a challenge inoculation on the 11th day in NC/Nga mice. On the 14th day, mice were examined for airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, mRNA expression of Th1 and Th2 cytokines in the lung tissue, and histopathology. Synergistic effects of Sup and Pre were observed as increases in AHR and a histopathological change of Periodic acid-Schiff (PAS) staining. Increases in neutrophils, macrophages, and lymphocytes of BALF cells were dependent on Pre. The expression of IL-4 mRNA was increased by Sup, and those of IL-5 mRNA and Il-13 mRNA was increased by Sup and Pre. Augmented AHR, mRNA expression of IL-4, peribronchial inflammation, and PAS staining by Sup plus Pre were attenuated by treatment of Sup with pronase to digest proteins. These results suggest that some proteins of ambient PM may be important environmental factors for AHR and airway inflammation with the aid of insoluble particulates, although some soluble factors such as endotoxins cannot be ruled out.

摘要

为了评估空气中颗粒物(PM)对气道的过敏效应,将悬浮 PM 中的可溶上清液(Sup)和不溶沉淀物(Pre)分离出来,接种到对螨过敏原高度敏感的 NC/Nga 小鼠体内。Sup、Pre 或两者的混合物,以及经蛋白酶处理或未经处理的混合物,通过鼻腔途径接种 5 次进行致敏,然后在第 11 天对 NC/Nga 小鼠进行激发接种。在第 14 天,检查小鼠的气道高反应性(AHR)、支气管肺泡灌洗液(BALF)细胞计数、肺组织中 Th1 和 Th2 细胞因子的 mRNA 表达以及组织病理学变化。Sup 和 Pre 的协同作用表现为 AHR 增加和过碘酸雪夫(PAS)染色的组织病理学变化。BALF 细胞中的中性粒细胞、巨噬细胞和淋巴细胞的增加依赖于 Pre。Sup 增加了 IL-4 mRNA 的表达,Sup 和 Pre 增加了 IL-5 mRNA 和 Il-13 mRNA 的表达。用蛋白酶处理 Sup 可减弱 Sup 加 Pre 引起的 AHR 增加、IL-4 mRNA 表达增加、支气管周围炎症和 PAS 染色。这些结果表明,环境 PM 中的一些蛋白质可能是 AHR 和气道炎症的重要环境因素,而不溶性颗粒可能起到辅助作用,尽管不能排除一些可溶性因素,如内毒素。

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