Complement Regulation of Th2 Functions in Lung Allergy

肺过敏中 Th2 功能的补体调节

• 批准号: 6534903
• 负责人: SCOTT M DROUIN
• 金额: $ 16.16万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6534903
• 关键词: Aspergillus; T lymphocyte; allergens; anaphylatoxins; asthma; bronchial mucus; cell type; complement pathway; complement receptor; computer data analysis; enzyme linked immunosorbent assay; eosinophilia; flow cytometry; genetically modified animals; host organism interaction; immediate hypersensitivity; immunoglobulin E; inflammation; laboratory mouse; lung lavage; pathologic process; plethysmography; polymerase chain reaction; receptor expression; single cell analysis; statistics /biometry

DESCRIPTION (provided by applicant): This career transition award will provide the necessary resources to assess the role of the complement system in asthma. Given that asthma is a major world-wide health problem, this research proposal will attempt to delineate the overall contribution of the complement system in the pathogenesis of asthma and, specifically, investigate the complement-mediated regulation of cell types that control asthma-associated responses. This hypothesis will be addressed through the use of an Aspergillus fumigatus animal model of pulmonary allergy utilizing mice that are deficient in the central component of the complement system C3 and the complement anaphylatoxin receptors which can contribute to airway hyperreactivity and inflammation. Furthermore, since Th2 and IgE responses are an important component of pulmonary allergy, and the role of complement has not been evaluated in regards to this facet, specific attention will be given to the ability of the complement system to regulate these asthma-associated responses. Collectively, this study will assess the expression, function, and participation of the complement system in airway inflammation during the course of asthma by evaluating asthma-associated responses such as airway hyperresponsiveness, lung eosinophilia, mucus hypersecretion, and Th2 and IgE responses in complement deficient and wild type animals. Moreover, results generated from this proposal will provide valuable insight into the contribution of the complement system in T cell regulation and allergy as well as pulmonary host defense and disease.

描述（由申请人提供）：该职业过渡奖将提供必要的资源来评估补体系统在哮喘中的作用。鉴于哮喘是全球范围内的主要健康问题，该研究建议将试图描述补体系统在哮喘发病机理中的总体贡献，并具体来说，研究了补体介导的调节控制哮喘相关反应的细胞类型的调节。该假设将通过使用烟草过敏的曲霉动物模型来解决该假设，利用小鼠的肺部过敏模型，这些小鼠在补体系统C3的中心成分以及补体过敏毒素受体中，这可能有助于空气过度反应性和炎症。此外，由于Th2和IgE反应是肺部过敏的重要组成部分，并且尚未评估补体的作用在这一方面，因此将特别注意补体系统调节这些哮喘相关反应的能力。总的来说，这项研究将通过评估哮喘相关反应，例如气道高反应性，肺嗜酸性嗜酸性症，粘液过度屈服，粘液过度反应，以及补体和野生型动物的Th2和IME反应，通过评估哮喘相关的反应（例如气道高反应性，肺嗜酸性嗜酸性和野生型动物），从而评估补体系统在气道炎症过程中的表达，功能和参与。此外，该提案产生的结果将为T细胞调节和过敏以及肺部宿主防御和疾病的贡献提供宝贵的见解。