Polymorphonuclear cell transmigration induced by Pseudomonas aeruginosa requires the eicosanoid hepoxilin A3
Polymorphonuclear cell transmigration induced by Pseudomonas aeruginosa requires the eicosanoid hepoxilin A3
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DOI：
10.4049/jimmunol.173.9.5712
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发表时间：
2004-11-01
影响因子：
4.4
通讯作者：
McCormick, BA
中科院分区：
文献类型：
--
作者：
Hurley, BP;Siccardi, D;McCormick, BA
在囊性纤维化和肺炎等疾病中，由呼吸道粘膜表面的细菌感染引起的肺部炎症对病理学有显著贡献。炎症反应的一个主要后果是在感染部位募集和积累多形核白细胞（PMN）。目前尚不清楚是什么细菌因素触发了这种反应，以及PMNs是如何穿过上皮屏障到达气道腔的。使用由在倒置的Transwell过滤器上生长的人PMN和肺泡上皮细胞（A549）组成的体外模型来确定细菌是否能够诱导PMN迁移穿过这些上皮屏障。许多肺部致病菌，包括肺炎克雷伯氏菌、大肠杆菌和铜绿假单胞菌确实能够诱导PMN迁移穿过A549单层。这种现象不是由LPS介导的，而是需要活细菌感染顶端表面。细菌与A549单层顶面的相互作用导致上皮反应的激活，包括ERK 1/2的磷酸化和PMN趋化因子IL-8的分泌。然而，IL-8的分泌在细菌感染的反应是既不必要，也不足以介导中性粒细胞跨上皮迁移。相反，PMN跨上皮迁移是由类花生酸类肝素A介导的（3），它是A549细胞以蛋白激酶G依赖性方式响应细菌感染而分泌的PMN化学引诱物。这些数据表明，细菌诱导的hepoxilin A（3）分泌可能代表了细菌感染时肺上皮内发生的一种以前未被认识到的炎症机制。
Lung inflammation resulting from bacterial infection of the respiratory mucosal surface in diseases such as cystic fibrosis and pneumonia contributes significantly to the pathology. A major consequence of the inflammatory response is the recruitment and accumulation of-polymorphonuclear cells (PMNs) at the infection site. It is currently unclear what bacterial factors trigger this response and exactly how PMNs are directed across the epithelial barrier to the airway lumen. An in vitro model consisting of human PMNs and alveolar epithelial cells (A549) grown on inverted Transwell filters was used to determine whether bacteria are capable of inducing PMN migration across these epithelial barriers. A variety of lung pathogenic bacteria, including Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa are indeed capable of inducing PMN migration across A549 monolayers. This phenomenon is not mediated by LPS, but requires live bacteria infecting the apical surface. Bacterial interaction with the apical surface of A549 monolayers results in activation of epithelial responses, including the phosphorylation of ERK1/2 and secretion of the PMN chemokine IL-8. However, secretion of IL-8 in response to bacterial infection is neither necessary nor sufficient to mediate PMN transepithelial migration. Instead, PMN transepithelial migration is mediated by the eicosanoid hepoxilin A(3), which is a PMN chemoattractant secreted by A549 cells in response to bacterial infection in a protein kinase G dependent manner. These data suggest that bacterial-induced hepoxilin A(3) secretion may represent a previously unrecognized inflammatory mechanism occurring within the lung epithelium during bacterial infections.