AIRWAY REMODELING--CELL-CELL INTERACTIONS

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DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) In chronic obstructive lung diseases such as asthma studies report structural changes in the airway wall including increases in smooth muscle mass. There is little information available with respect to factors that control the mass of the various cells which constitute the airway wall and it is unclear whether increases in mass occur via hyperplasia or hypertrophy of the resident cells. The overall goal of this project is to define the interaction of airway epithelial cells, smooth muscle cells and fibroblasts in terms of cell growth. The overall working hypothesis is that airway epithelial cells, smooth muscle cells, fibroblasts and the matrix surrounding them interact in a complex fashion and this interaction is responsible for the structure of the airway wall. In conditions associated with airway injury, such as hyperoxia, the normal cell-cell interactions and production of growth modulating factors is disrupted, inducing altered airway structure and function. The Specific Aims are: 1) to compare the pattern of response of individual cells within airway organ cultures to that of isolated epithelial cells, smooth muscle cells and fibroblasts in response to selected growth factors; 2) to assess the interaction of the cells in the airway wall; 3) to compare the pattern of response of individual cells within airway organ cultures to that of isolated epithelial cells, smooth muscle cells and fibroblasts in response to oxygen induced injury, and 4) to determine how cell: cell interactions modulate the cellular response to oxygen induced injury. These experiments could provide important new insights into the factors responsible for the maintenance of normal airway structure and the remodeling response associated with injury and asthma.