Airway Inflammation: Bacterial Epithelial Interactions

描述(申请人提供)：由细菌感染引起的肺部疾病在许多情况下以严重炎症为特征，特别是沿呼吸道的管腔内大量中性粒细胞积聚。目前尚不清楚哪些细菌因素可以触发这种反应，以及中性粒细胞是如何被引导到感染部位的。在这项建议的初步数据中，我们利用极化的肺泡上皮单层和中性粒细胞建立了一个呼吸道炎症的体外模型。我们已经证明，各种细菌能够诱导中性粒细胞跨肺泡上皮单层迁移。这一现象似乎不是由内毒素介导的，而且诱导中性粒细胞迁移的机制独立于IL-8的分泌，本研究的目的是确定促进中性粒细胞迁移的细菌因素，并进一步确定上皮单层在这一过程中的作用。从以下建议中获得的结果可能有助于阐明涉及细菌介导的肺部炎症的疾病，如囊性纤维化，也将为治疗肺部疾病提供新的策略。

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.