Ciencewicki Jonathan, Gowdy Kymberly, Krantz Quentin T, Linak William P, Brighton Luisa, Gilmour M Ian, Jaspers Ilona
Curriculum of Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA.
Inhal Toxicol. 2007 Nov;19(14):1121-33. doi: 10.1080/08958370701665426.
We have previously shown that exposure of respiratory epithelial cells to diesel exhaust (DE) enhances susceptibility to influenza infection and increases the production of interleukin (IL)-6 and interferon (IFN)-beta. The purpose of this study was to confirm and expand upon these in vitro results by assessing the effects of DE exposure on the progression of influenza infection and on development of associated pulmonary immune and inflammatory responses in vivo. BALB/c mice were exposed to air or to DE containing particulate matter at concentrations of 0.5 or 2 mg/m(3) for 4 h/day for 5 days and subsequently instilled with influenza A/Bangkok/1/79 virus. Exposure to 0.5 mg/m(3) (but not the higher 2-mg/m(3) dose) of DE increased susceptibility to influenza infection as demonstrated by a significant increase in hemagglutinin (HA) mRNA levels, a marker of influenza copies, and greater immunohistochemical staining for influenza virus protein in the lung. The enhanced susceptibility to infection observed in mice exposed to 0.5 mg/m(3) of DE was associated with a significant increase in the expression of IL-6, while antiviral lung IFN levels were unaffected. Analysis of the expression and production of surfactant proteins A and D, which are components of the interferon-independent antiviral defenses, showed that these factors were decreased following exposure to 0.5 mg/m(3) of DE but not to the higher 2-mg/m(3) concentration. Taken together, the results demonstrate that exposure to DE enhances the susceptibility to respiratory viral infections by reducing the expression and production of antimicrobial surfactant proteins.
我们之前已经表明，呼吸道上皮细胞暴露于柴油废气（DE）会增强对流感感染的易感性，并增加白细胞介素（IL）-6和干扰素（IFN）-β的产生。本研究的目的是通过评估DE暴露对流感感染进程以及体内相关肺部免疫和炎症反应发展的影响，来证实并扩展这些体外实验结果。将BALB/c小鼠暴露于空气或浓度为0.5或2 mg/m³的含颗粒物的DE中，每天暴露4小时，持续5天，随后接种甲型/曼谷/1/79流感病毒。暴露于0.5 mg/m³（而非更高的2 mg/m³剂量）的DE会增加对流感感染的易感性，这表现为血凝素（HA）mRNA水平显著升高（流感病毒拷贝数的一个指标）以及肺中流感病毒蛋白的免疫组化染色更强。在暴露于0.5 mg/m³ DE的小鼠中观察到的感染易感性增强与IL-6表达的显著增加相关，而抗病毒肺干扰素水平未受影响。对作为不依赖干扰素的抗病毒防御成分的表面活性蛋白A和D的表达及产生进行分析表明，暴露于0.5 mg/m³ DE后这些因子减少，但暴露于更高的2 mg/m³浓度时则未减少。综上所述，结果表明暴露于DE会通过降低抗菌表面活性蛋白的表达和产生来增强对呼吸道病毒感染的易感性。
