Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness.
Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness.
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呼吸道合胞病毒感染会增加氯引起的气道高反应性。
DOI：
10.1152/ajplung.00159.2015
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Matalon,Sadis
中科院分区：
文献类型：
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作者：
Song,Weifeng;Yu,Zhihong;Doran,StephenF;Ambalavanan,Namasivayam;Steele,Chad;Garantziotis,Stavros;Matalon,Sadis
暴露于氯（Cl 2）会损伤气道和肺泡上皮细胞，导致急性肺损伤和对乙酰甲胆碱的反应性气道高反应性（AHR）。然而，鲜为人知的是，预先存在的呼吸系统疾病对氯诱导的肺损伤的影响。通过使用鼠呼吸道合胞病毒（RSV）感染模型，我们发现，预先存在的RSV感染增加Cl 2（187 ppm，30分钟）诱导的肺部炎症和气道AHR在暴露后24小时（感染后5天）。RSV感染和Cl 2暴露协同诱导氧饱和度下降和中性粒细胞浸润，并增加支气管肺泡灌洗液（BALF）中MCP-1、MIP-1β、IL-10、IFN-γ和RANTES浓度。相反，2型细胞因子（即，IL-4、IL-5、IL-9和IL-13）不受RSV感染或Cl 2暴露的显著影响。通过flexiVent测定，氯暴露（而非RSV感染）诱导乙酰甲胆碱激发的AHR。此外，预先存在的RSV感染放大BALF中的透明质酸（HA）和AHR水平。用α-胰蛋白酶间抑制剂抗体处理可减轻Cl 2诱导的AHR，该抗体抑制HA信号传导，提示HA介导的AHR是由氧化损伤加剧引起的。我们的研究结果首次表明，预先存在的RSV感染易使肺受到Cl 2诱导的损伤。这些数据强调了进一步研究Cl 2在弱势群体中的影响和开发适当治疗方法的必要性。
Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2(187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2exposure. Cl2exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2in vulnerable populations and the development of appropriate treatments.