Airway Inflammation and Airway Remodeling

描述（由申请人提供）：这是一项哮喘和过敏性疾病合作研究中心（AADCRC）的新申请，由加州大学圣地亚哥分校医学院和两个邻近的拉霍亚研究所的研究人员组成，他们在哮喘、免疫学、分子生物学和CT扫描成像方面具有专业知识。该申请由四个相互关联的基础科学研究项目组成，重点关注气道重塑的细胞和分子机制，由两个量化气道重塑的科学核心（CT成像核心；组织学核心）和一个行政核心支持。该项目的科学主题和长期目标是提高我们对气道炎症在气道细胞水平上介导气道重塑的分子机制的理解，并开发更好地可视化小鼠和人体内气道重塑的方法。该项目中的小鼠研究将利用过敏原诱导的气道重塑小鼠模型和利用微ct扫描成像气道重塑。与此同时，人体研究将利用通过BAL、支气管刷毛和活检获得的气道重塑患者的标本，其中进行气道重塑的相关CT扫描成像。项目1 （Broide）将重点关注肥大细胞在介导气道重塑中的作用。项目2 （Sriramarao）将专注于了解内皮细胞上表达的碳水化合物如何促进祖细胞从骨髓到肺的运输并促进重塑。项目3 （Croft）将专注于了解招募到气道的CD4+ T细胞如何促进平滑肌重塑。项目4 （Zuraw）将重点了解气道上皮间质单位如何促进气道重塑。慢性哮喘可能与一些中度至重度哮喘患者的支气管瘢痕有关，这可能会损害空气流通。该项目通过研究哮喘发作如何导致支气管瘢痕形成，以及通过使用CAT扫描x射线早期检测有瘢痕形成风险的哮喘患者的支气管瘢痕形成，开发支气管瘢痕形成的早期检测方法。

DESCRIPTION (provided by applicant): This is a new application for an Asthma and Allergic Diseases Cooperative Research Center (AADCRC) by a team of investigators at the UCSD School of Medicine and two neighboring La Jolla research institutes with expertise in asthma, immunology, molecular biology, and CT scan imaging. The application consists of four interrelated basic science research projects that focus on cellular and molecular mechanisms of airway remodeling, supported by two scientific cores to quantitate airway remodeling (CT imaging core; histology core),and an administrative core. The scientific theme and long term objective of this project is to improve our understanding of the molecular mechanisms of airway inflammation mediating airway remodeling at a cellular level in the airway, and develop methods to better visualize airway remodeling in vivo in both mouse and man. The mouse studies in the program project will utilize a mouse model of allergen induced airway remodeling and image airway remodeling utilizing microCT scanning. In parallel, human studies will utilize specimens from human asthmatics with airway remodeling obtained by BAL, bronchial brushing, and biopsy in which associated CT scan imaging of airway remodeling is performed. Project 1 (Broide) will focus on the role of mast cells in mediating airway remodeling. Project 2 (Sriramarao) will focus on understanding how carbohydrates expressed on endothelial cells contribute to trafficking of progenitor cells from the bone marrow to the lung and contribute to remodeling. Project 3 (Croft) will focus on understanding how CD4+ T cells recruited to the airway contribute to smooth muscle remodeling. Project 4 (Zuraw) will focus on understanding how the airway epithelial mesenychymal unit contributes to airway remodeling. Chronic asthma may be associated in some moderate to severe asthmatics with scarring of their bronchial tubes which may impair air flow. This program project is developing methods for the early detection of scarring of the bronchial tubes by studying how asthma attacks lead to scarring of the bronchial tubes, as well as by using CAT scan X-Rays for early detection of scarring of the bronchial tubes in asthmatics at risk for scarring.