Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK.
Clin Exp Allergy. 2009 Oct;39(10):1597-610. doi: 10.1111/j.1365-2222.2009.03302.x. Epub 2009 Jun 22.
Inhaled house dust mite (HDM) results in T-helper (TH) 2 type pathology in unsensitized mice, in conjunction with airway hyperreactivity and airway remodelling. However, the pulmonary cytokine and chemokine profile has not been reported.
We have performed a time course analysis of the characteristic molecular mediators and cellular influx in the bronchoalveolar lavage (BAL) and lung in order to define the pulmonary inflammatory response to inhaled HDM extract. Mice were exposed five times a week to soluble HDM extract for 3 weeks. Lung function was measured in groups of mice at intervals following the final HDM challenge. Recruitment of inflammatory cells and inflammatory mediator production was then assessed in BAL and lungs of individual mice.
We found that Th2 cytokines were significantly increased in BAL and lung after HDM challenge from as early as 2 h post-final challenge. The levels of cytokines and chemokines correlated with the influx of eosinophils and Th2 cells to the different compartments of the lung. However, the production of key cytokines such as IL-4, IL-5 and IL-13 preceded the increase in airways resistance.
Inhaled HDM challenge induces a classical Th2 inflammatory mediator profile in the BAL and lung. These data are important for studies determining the efficacy of novel treatment strategies for allergic airways disease.
吸入屋尘螨(HDM)会导致未致敏小鼠产生 TH2 型病理学反应,同时伴有气道高反应性和气道重塑。然而,肺部细胞因子和趋化因子的特征尚未被报道。
我们对特征分子介质和支气管肺泡灌洗液(BAL)及肺部中的细胞内流进行了时间进程分析,以便确定吸入 HDM 提取物引起的肺部炎症反应。每周 5 次,将小鼠暴露于可溶性 HDM 提取物中 3 周。在最后一次 HDM 挑战后,每隔一段时间测量一组小鼠的肺功能。然后评估单个小鼠的 BAL 和肺中的炎症细胞募集和炎症介质产生情况。
我们发现,在最后一次 HDM 挑战后 2 小时,BAL 和肺中的 Th2 细胞因子明显增加。细胞因子和趋化因子的水平与嗜酸性粒细胞和 Th2 细胞向肺部不同部位的流入相关。然而,关键细胞因子如 IL-4、IL-5 和 IL-13 的产生先于气道阻力的增加。
吸入 HDM 挑战会引起 BAL 和肺部中的经典 Th2 炎症介质特征。这些数据对于确定新型治疗策略治疗过敏性气道疾病的疗效的研究很重要。