IL5 AND OVA INDUCED RESPIRATORY INFLAMMATION

该提案试图定义肺中导致肺病理学和肺功能障碍的IL-5效应器功能。 该提案的重点是使用从气道上皮细胞组成性表达IL-5的哮喘转基因小鼠模型（品系NJ. 1726）鉴定IL-5依赖性细胞和分子肺变化。 具体而言，该提议将使NJ. 1726小鼠中发生的诱导的肺部病理（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相关。 我们还将确定肺中IL-5表达诱导的肺变化是否使个体对暴露于雾化抗原的加重效应“敏感”（即，过敏性炎症）。 此外，该提案概述了鉴定肺中白细胞特异性活性和评估IL-5表达对其他炎症信号级联的协同作用的具体实验。 该提案的一个重要目的是将这些遗传方法与小鼠中伴随过敏性呼吸道炎症的下游肺部后果相结合。 本建议的具体目标是：（1）确定淋巴细胞依赖性（即，T和B细胞的特定亚群）的肺病理学的研究（系NJ. 1726）;（2）为了评估IL-5作为炎性信号在肺中发生的I型超敏反应中的作用（即，过敏性肺炎）;（3）测试IL-5和肺中表达的趋化因子之间的协同效应是否是在暴露于变应原的小鼠和哮喘患者中观察到的肺病理的原因。

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.