Department of Pulmonary Medicine, Erasmus MC Rotterdam, The Netherlands.
Clin Exp Allergy. 2010 Mar;40(3):494-504. doi: 10.1111/j.1365-2222.2009.03417.x. Epub 2009 Nov 25.
Allergic rhinitis (AR) and asthma often coexist and are referred to as 'united airways' disease. However, the molecular and cellular pathways that are crucially involved in the interaction between upper and lower airways remain to be identified.
We sought to assess whether and how AR exacerbates lower airway inflammation upon allergen challenge in mice.
We previously developed an intranasal ovalbumin (OVA)-driven AR model, characterized by nasal eosinophilic inflammation, enhanced serum levels of OVA-specific IgE and Th2 cytokine production in cervical lymph nodes. In OVA-sensitized mice with or without AR, a lower airway challenge was given, and after 24 h, lower airway inflammation was analysed.
We found that AR mice were more susceptible to eosinophilic inflammation following a lower airway OVA challenge than OVA-sensitized controls. AR mice manifested increased numbers of eosinophils in bronchoalveolar lavage fluid and increased inter-cellular adhesion molecule-1 (ICAM-1) expression on lung endothelium, when compared with OVA-sensitized controls. Depletion of T cells in OVA-challenged AR mice completely abrogated all hallmarks of lower airway inflammation, including enhanced IL-5 and tissue eosinophilia. Conversely, adoptive transfer of Th2 effector cells in naïve animals induced lower airway eosinophilic inflammation after challenge with OVA. Blocking T cell recirculation during AR development by the spingosine-1 analogue FTY720 also prevented lower airway inflammation including ICAM-1 expression in AR mice upon a single lower airway challenge.
Our mouse model of 'united airways' disease supports epidemiological and clinical data that AR has a significant impact on lower airway inflammation. Circulating Th2 effector cells are responsible for lung priming in AR mice, most likely through up-regulation of ICAM-1.
过敏性鼻炎（AR）和哮喘常同时存在，被称为“联合气道”疾病。然而，在上、下气道相互作用中起关键作用的分子和细胞途径仍有待确定。
我们旨在评估 AR 是否以及如何在变应原激发下加重小鼠下气道炎症。
我们之前开发了一种鼻内卵清蛋白（OVA）驱动的 AR 模型，其特征为鼻嗜酸性粒细胞炎症、血清 OVA 特异性 IgE 水平升高和颈部淋巴结 Th2 细胞因子产生增加。在有或没有 AR 的 OVA 致敏小鼠中，进行下气道激发，24 小时后分析下气道炎症。
我们发现，与 OVA 致敏对照小鼠相比，AR 小鼠在下气道 OVA 激发后更容易发生嗜酸性粒细胞炎症。与 OVA 致敏对照小鼠相比，AR 小鼠支气管肺泡灌洗液中的嗜酸性粒细胞增多，肺内皮细胞间黏附分子-1（ICAM-1）表达增加。在 OVA 激发的 AR 小鼠中耗尽 T 细胞可完全消除下气道炎症的所有特征，包括增强的 IL-5 和组织嗜酸性粒细胞增多。相反，在 OVA 激发前将 Th2 效应细胞过继转移到 naive 动物中，可诱导下气道嗜酸性粒细胞炎症。在 AR 发展过程中通过鞘氨醇-1 类似物 FTY720 阻断 T 细胞再循环也可防止 AR 小鼠在下一次下气道激发时发生下气道炎症，包括 ICAM-1 表达。
我们的“联合气道”疾病小鼠模型支持流行病学和临床数据，即 AR 对下气道炎症有重大影响。循环 Th2 效应细胞负责 AR 小鼠的肺部致敏，可能是通过上调 ICAM-1。
