Ogino Keiki, Zhang Ran, Takahashi Hidekazu, Takemoto Kei, Kubo Masayuki, Murakami Ikuo, Wang Da-Hong, Fujikura Yoshihisa
Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Public Health, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
PLoS One. 2014 Mar 26;9(3):e92710. doi: 10.1371/journal.pone.0092710. eCollection 2014.
To evaluate the effect of airborne particulate matter 2.5 (PM2.5) in winter on airway inflammation, water-soluble supernatant (Sup) and water-insoluble precipitate (Pre) in PM2.5 were inoculated in NC/Nga mice with high sensitivity to mite allergens. Sup with aluminum oxide was injected intraperitoneally for sensitization. Five days later, Sup, Pre or both Sup and Pre were inoculated via the nasal route five times for more sensitization and a challenge inoculation on the 11th day in NC/Nga mice. On the 12th day, mice were examined for airway hyperresponsiveness (AHR), BALF cell count and IL-1β concentration, mRNA expression of Th1 and Th2 cytokines, chemokines such as eotaxin 1 and eotaxin 2, inflammasomal complex molecules such as IL-1β, caspase 1 and the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) in lung tissue as well as histopathology. The synergistic effect of Sup and Pre was observed in terms of increases in AHR, BALF cells, the mRNA expression of IL-13, eotaxin1 and IL-1β, and the IL-1β concentration in BALF. Intracellular deposits of insoluble particulates were observed in macrophages around inflammatory granulation of the mouse group treated with Sup and Pre. These results suggest that PM2.5 can induce airway hyperresponsiveness in mice with genetically high sensitivity to mite allergens by an inflammasome-associated mechanism and synergistic action of insoluble particulates and soluble components.
为评估冬季空气中细颗粒物2.5（PM2.5）对气道炎症的影响，将PM2.5中的水溶性上清液（Sup）和水不溶性沉淀物（Pre）接种于对螨过敏原高度敏感的NC/Nga小鼠。用含氧化铝的Sup进行腹腔注射致敏。五天后，通过鼻腔途径对NC/Nga小鼠进行五次Sup、Pre或Sup与Pre联合接种以加强致敏，并在第11天进行激发接种。在第12天，检测小鼠的气道高反应性（AHR）、支气管肺泡灌洗液（BALF）细胞计数和IL-1β浓度、Th1和Th2细胞因子的mRNA表达、趋化因子如嗜酸性粒细胞趋化因子1和嗜酸性粒细胞趋化因子2、肺组织中炎性小体复合物分子如IL-1β、半胱天冬酶1和核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）以及组织病理学。在AHR增加、BALF细胞、IL-13、嗜酸性粒细胞趋化因子1和IL-1β的mRNA表达以及BALF中IL-1β浓度方面观察到Sup和Pre的协同作用。在用Sup和Pre处理的小鼠组炎症肉芽周围的巨噬细胞中观察到不溶性颗粒的细胞内沉积。这些结果表明，PM2.5可通过炎性小体相关机制以及不溶性颗粒和可溶性成分的协同作用，在对螨过敏原具有遗传高敏感性的小鼠中诱导气道高反应性。
