Increased susceptibility to RSV infection by exposure to inhaled diesel engine emissions
Increased susceptibility to RSV infection by exposure to inhaled diesel engine emissions
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DOI：
10.1165/rcmb.2002-0100oc
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发表时间：
2003-04-01
影响因子：
6.4
通讯作者：
Reed, MD
中科院分区：
文献类型：
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作者：
Harrod, KS;Jaramillo, RJ;Reed, MD
尽管流行病学数据强烈表明吸入环境污染物在调节人类呼吸道感染易感性中的作用，但在实验系统中尚未充分研究潜在的细胞和分子机制。本研究评估了吸入柴油发动机排放物（DEE）对体内宿主对常见儿科呼吸道病原体呼吸道合胞病毒（RSV）反应的影响。使用RSV感染的相对抗性小鼠模型，与暴露于空气中的RSV感染的C57 BI/6小鼠相比，先前暴露于30 μ g/m3颗粒物（PM）或1，000 μ g/m3 PM吸入DEE（6 h/d，连续7天）增加了RSV感染的肺部炎症。支气管肺泡灌洗液中的炎症细胞以剂量依赖性方式增加，与DEE暴露水平相关，同时伴有炎症介质水平增加。肺组织学分析表明，明显的支气管周围和细支气管周围炎症与感染期间DEE暴露水平一致。RSV感染后，DEE暴露小鼠气道上皮中的粘液细胞化生显著增加。有趣的是，气道和肺泡宿主防御和免疫调节蛋白在RSV感染期间通过先前的DEE暴露而减弱。DEE诱导的炎症和肺上皮细胞对感染的反应变化与DEE暴露后肺部RSV基因表达增加相关。这些发现与DEE暴露调节肺部宿主对呼吸道病毒感染的防御，并可能改变对呼吸道感染的易感性，导致肺部疾病增加的概念一致。
Although epidemiologic data strongly suggest a role for inhaled environmental pollutants in modulating the susceptibility to respiratory infection in humans, the underlying cellular and molecular mechanisms have not been well studied in experimental systems. The current study assessed the impact of inhaled diesel engine emissions (DEE) on the host response in vivo to a common pediatric respiratory pathogen, respiratory syncytial virus (RSV). Using a relatively resistant mouse model of RSV infection, prior exposure to either 30 mug/m(3) particulate matter (PM) or 1,000 mug/m(3) PM of inhaled DEE (6 h/d for seven consecutive days) increased lung inflammation to RSV infection as compared with air-exposed RSV-infected C57BI/6 mice. Inflammatory cells in bronchoalveolar lavage fluid were increased in a dose-dependent manner with regard to the level of DEE exposure, concomitant with increased levels of inflammatory mediators. Lung histology analysis indicated pronounced peribronchial and peribronchiolar inflammation concordant with the level of DEE exposure during infection. Mucous cell metaplasia was markedly increased in the airway epithelium of DEE-exposed mice following RSV infection. Interestingly, both airway and alveolar host defense and immunomodulatory proteins were attenuated during RSV infection by prior DEE exposure. DEE-induced changes in inflammatory and lung epithelial responses to infection were associated with increased RSV gene expression in the lungs following DEE exposure. These findings are consistent with the concept that DEE exposure modulates the lung host defense to respiratory viral infections and may alter the susceptibility to respiratory infections leading to increased lung disease.