viruses are the most common etiologic agents for childhood airway and lung infections and provoke a complex interplay of injury, inflammatory response and repair. This SCOR will focus on the Airway Epithelial Response to Childhood Viral Infection, with each proposed project addressing an aspect of the pathobiology of respiratory viral infection in the airway epithelium. Central to this SCOR is examination of cytokine/chemokine production in the respiratory tract during naturally acquired respiratory syncytial virus (RSV) infection in children and experimental RSV infection in adult volunteers (Project II). Clinical samples and findings from this project will be available to other projects to study the mucosal derived factors in the injury, inflammatory response, and repair process. The injury and repair process of airway epithelium will be addressed in Projects I and III. Project I will examine airway epithelial phenotypic changes in response to injury, using ciliated cell specific markers and exogenous markers to track ciliated cells during injury and repair in both animal models and human cell culture models. Project III will define the role of insulin-like growth factor-I in the repair process and examine the potential role of this growth factor in improving epithelial cell survival following injury. Inflammatory cell recruitment to the lung during respiratory viral infections will be examined in Projects IV and V. Project IV will define the roles of beta-chemokine in the recruitment of lymphocytes during influenza virus infection using animal models. The emigration of neutrophils will be examined in Project V by examining the alteration in endothelial cell adhesion molecules during the inflammatory process and in human endothelial cells. In addition to viral infection models, non- infectious injury models such as sulfur dioxide and oxygen exposure will be used to characterize airway epithelial cell injury without the immunologic responses triggered by viral infection. Each project is supported by the four Cores, administrative, Morphology/Ultrastructure, Molecular Biology, and Virology/Immunology. These Cores will function to centralize equipment, reagents and various laboratory procedures to facilitate the research efforts of the SCOR investigators.
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