Airway Inflammation: Bacterial Epithelial Interactions

描述（由申请人提供）：在许多情况下，细菌感染导致的肺部疾病以严重炎症为特征，特别是大量中性粒细胞沿着呼吸道沿着在管腔空间中积聚。目前尚不清楚什么细菌因素可以触发这种反应，以及中性粒细胞如何被引导到感染部位。在这个建议的初步数据中，我们已经开发了一种使用极化肺泡上皮细胞单层和中性粒细胞的气道炎症体外模型。我们已经证明，多种细菌能够诱导中性粒细胞穿越肺泡上皮细胞单层。这种现象似乎不是由LPS介导的，并且诱导中性粒细胞迁移的机制不依赖于IL-8分泌。该提议的目的是鉴定负责促进中性粒细胞迁移的细菌因子以及进一步确定上皮单层在该过程中的作用。从以下建议中获得的结果可能揭示涉及细菌介导的肺部炎症如囊性纤维化的疾病，并且还应该提供针对治疗肺部疾病的新策略。

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.