Airway Inflammation: Bacterial Epithelial Interactions

描述（由申请人提供）：在许多情况下，由细菌感染引起的肺部疾病以严重的炎症为特征，特别是在呼吸道的腔隙中积累大量中性粒细胞。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。在本提案的初步数据中，我们已经开发了一个使用极化肺泡上皮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跨肺泡上皮单层迁移。这一现象似乎不是由LPS介导的，诱导中性粒细胞迁移的机制与IL-8分泌无关。本研究旨在确定促进中性粒细胞迁移的细菌因子，并进一步明确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会揭示涉及细菌介导的肺部炎症的疾病，如囊性纤维化，也应该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.