A role for airway remodeling during respiratory syncytial virus infection
A role for airway remodeling during respiratory syncytial virus infection
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DOI：
10.1186/1465-9921-6-122
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发表时间：
2005-10-21
影响因子：
5.8
通讯作者：
Cormier, SA
中科院分区：
文献类型：
--
作者：
Becnel, D;You, DH;Cormier, SA
背景资料：婴儿期严重呼吸道合胞病毒感染（RSV）已被证明是随后发生喘息的主要危险因素。然而，这种联系的原因尚不清楚。本研究的目的是确定的后果早期暴露于RSV和过敏原在随后的气道高反应性（AHR）的发展中使用的发展时间点在小鼠平行的人neonates.Methods：断奶小鼠致敏和挑战卵清蛋白（Ova）和/或感染RSV。八天后，最后一次过敏原的挑战，各种病理生理学终点examined.Results：AHR在乙酰甲胆碱反应增强，只有在断奶小鼠暴露于OVA，随后感染RSV。AHR的增加似乎与肺RSV滴度无关。这些小鼠的总支气管肺泡灌洗液细胞数相对于单独使用Ova增加约2倍，这归因于嗜酸性粒细胞和淋巴细胞数量的增加。观察到肺病理学增强，包括持续性粘液产生和上皮下纤维化。有趣的是，这些数据与TNF-α，IFN-γ，IL-5和IL-2的一过性升高相关。结论：观察到的肺结构变化可能为流行病学数据提供了解释，表明早期暴露于过敏原和RSV具有长期的生理后果。此外，本文提供的数据强调了在新生儿发育期间针对特应性个体的RSV感染的预防策略的重要性。
Background: Severe respiratory syncytial virus infection (RSV) during infancy has been shown to be a major risk factor for the development of subsequent wheeze. However, the reasons for this link remain unclear. The objective of this research was to determine the consequences of early exposure to RSV and allergen in the development of subsequent airway hyperreactivity (AHR) using a developmental time point in the mouse that parallels that of the human neonate.Methods: Weanling mice were sensitized and challenged with ovalbumin ( Ova) and/or infected with RSV. Eight days after the last allergen challenge, various pathophysiological endpoints were examined.Results: AHR in response to methacholine was enhanced only in weanling mice exposed to Ova and subsequently infected with RSV. The increase in AHR appeared to be unrelated to pulmonary RSV titer. Total bronchoalveolar lavage cellularity in these mice increased approximately two-fold relative to Ova alone and was attributable to increases in eosinophil and lymphocyte numbers. Enhanced pulmonary pathologies including persistent mucus production and subepithelial fibrosis were observed. Interestingly, these data correlated with transient increases in TNF-alpha, IFN-gamma, IL-5, and IL-2.Conclusion: The observed changes in pulmonary structure may provide an explanation for epidemiological data suggesting that early exposure to allergens and RSV have long-term physiological consequences. Furthermore, the data presented here highlight the importance of preventative strategies against RSV infection of atopic individuals during neonatal development.