Airway Inflammation and Airway Remodeling

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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.