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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL056395-04
Application #
6125806
Study Section
Special Emphasis Panel (ZHL1-CSR-Q (M1))
Project Start
1996-12-01
Project End
2001-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
4
Fiscal Year
2000
Total Cost
$1,617,467
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Pediatrics
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Volberg, T; Romer, L; Zamir, E et al. (2001) pp60(c-src) and related tyrosine kinases: a role in the assembly and reorganization of matrix adhesions. J Cell Sci 114:2279-89
Noah, T L; Becker, S (2000) Chemokines in nasal secretions of normal adults experimentally infected with respiratory syncytial virus. Clin Immunol 97:43-9
Veness-Meehan, K A; Bottone Jr, F G; Stiles, A D (2000) Effects of retinoic acid on airspace development and lung collagen in hyperoxia-exposed newborn rats. Pediatr Res 48:434-44

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