IL5 AND OVA INDUCED RESPIRATORY INFLAMMATION

本研究旨在明确IL-5在肺中导致肺病理和肺功能障碍的效应功能。该提案的重点是利用气道上皮组成性表达IL-5的转基因哮喘小鼠模型（系NJ.1726）来鉴定IL-5依赖性细胞和分子肺变化。具体地说，该建议将NJ.1726小鼠中发生的诱导肺病理（包括气道高反应性的测量）与嗜酸性粒细胞和特定淋巴细胞亚群的募集联系起来。我们还将确定肺中IL-5表达诱导的肺变化是否会使个体对暴露于雾化抗原（即过敏性炎症）的加重效应“敏感”。此外，该提案概述了特异性实验，以确定肺中白细胞特异性活动，并评估IL-5表达对其他炎症信号级联的协同作用。本提案的一个重要目的是将这些遗传方法与伴随过敏性呼吸道炎症的下游肺部后果整合在小鼠中。该提案的具体目标是：(1)确定在肺中组成性表达IL-5的转基因小鼠（NJ.1726系）中发生的肺部病变的淋巴细胞依赖性（即T细胞和B细胞的特定亚群）；(2)评估IL-5作为炎症信号在肺i型超敏反应（即过敏性肺部炎症）中的作用；(3)检测IL-5与肺中表达的趋化因子之间的协同作用是否与暴露于过敏原的小鼠和哮喘患者肺部病变有关。

This proposal seeks to define IL-5 effector functions in the lung leading to pulmonary pathology and lung dysfunction. The focus of the proposal is to identify IL-5-dependent cell and molecular pulmonary changes using a transgenic mouse model of asthma constitutively expressing IL-5 from the airway epithelium (line NJ.1726). Specifically, this proposal will correlate induced pulmonary pathologies (including measurements of airway hyper- responsiveness) occurring in NJ.1726 mice with the recruitment of eosinophils and specific lymphocyte subpopulations. We will also determine if pulmonary changes induced by IL-5 expression in the lung "sensitize" individuals to exacerbating effects of exposure to aerosolized antigen (i.e., allergic inflammation). Moreover, the proposal outlines specific experiments to identify leukocyte- specific activities in the lung and to evaluate the synergistic effect of IL-5 expression on the other inflammatory signaling cascades. An important intent of this proposal is to integrate these genetic approaches in the mouse with the downstream pulmonary consequences accompanying allergic respiratory inflammation. The specific objectives of this proposal are: (1) To determine the lymphocyte dependence (i.e., the specific subpopulations of T and B cells) of the pulmonary pathologies occurring in transgenic mice constitutively expressing IL-5 in the lung (line NJ.1726); (2) To assess the contribution of IL-5 as an inflammatory signal in type I-hypersensitivity reactions occurring in the lung (i.e., allergic pulmonary inflammation); (3) To test if synergistic effects between IL-5 and chemokines expressed in the lung are responsible for lung pathologies observed in mice and asthmatic patients exposed to allergens.