Airway Inflammation: Bacterial Epithelial Interactions

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DESCRIPTION (provided by applicant): Lung disease as a consequence of bacterial infection in many situations is marked by severe inflammation, particularly the accumulation of large numbers of neutrophils in the luminal space along the respiratory tract. It is currently unclear what bacterial factors can trigger this response and exactly how the neutrophils are directed to the site of infection. In the preliminary data of this proposal we have developed an in vitro model for airway inflammation using polarized alveolar epithelial monolayers and neutrophils. We have shown that a variety of bacteria are capable of inducing neutrophil transmigration across the alveolar epithelial monolayers. This phenomenon does not appear to be mediated by LPS and the mechanism of induction of neutrophil transmigration is independent of IL-8 secretion, It is the intention of this proposal to identify the bacterial factors responsible for promoting the neutrophil migration as well as to further define the role of the epithelial monolayer in this process. Results obtained from the following proposal may shed light on diseases involving bacterial mediated lung inflammation such as cystic fibrosis and should also provide new strategies directed towards treating lung disease.