REGULATION OF ICAM-1 IN ALVEOLAR EPITHELIAL CELLS

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DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) Intercellular adhesion molecule-1 (ICAM-1) is a cell surface adhesion protein that plays an important role for lymphocyte and monocyte adherence and migration and is involved in the transduction of critical co-stimulatory signals for the activation of T cells. The overall goal of the application is to elucidate the regulation of ICAM-1 expression in alveolar epithelial cells in vitro. To accomplish this objective, experiments will be performed examining primary cultures of rat cells isolated as type II epithelial cells which undergo in vitro differentiation towards the type I cell phenotype. Specific Aim I will delineate the roles of a selected set of signals that may be involved in the control of alveolar epithelial cell ICAM-1 expression. Specific Aim 2 will investigate the molecular biology of ICAM-1 regulation in alveolar epithelial cells, focusing of the roles of protein and mRNA turnover, and initiation and elongation of mRNA transcription. In addition, data suggest that ICAM-1 is associated with cytoskeletal elements, and the functional activity of ICAM-1 may depend on the interaction with the cytoskeleton. Specific Aim 3 will determine the nature and regulation of this interaction between ICAM-1 and the cytoskeleton. Thus this project proposes to define the regulation of alveolar epithelial ICAM-1 expression from the initiation of transcription of the gene to the macromolecular associations at the cell surface. The work may provide insights into the regulation of epithelial cell differentiation in the alveolar space and may provide insights into the expression of a molecule which may play a critical role in defining the immunologic milieu of the alveolar space.