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首页> 外文期刊>Infection and immunity >Antimicrobial Activity of Murine Lung Cells against Staphylococcus aureus Is Increased In Vitro and In Vivo after Elafin Gene Transfer
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Antimicrobial Activity of Murine Lung Cells against Staphylococcus aureus Is Increased In Vitro and In Vivo after Elafin Gene Transfer

机译：Elafin基因转移后，体外和体内鼠肺细胞对金黄色葡萄球菌的抗菌活性增加。

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Staphylococcus aureus is a pathogen often found in pneumonia and sepsis. In the context of the resistance of this organism to conventional antibiotics, an understanding of the regulation of natural endogenous antimicrobial molecules is of paramount importance. Previous studies have shown that both human and mouse airways express a variety of these molecules, including defensins, cathelicidins, and the four-disulfide core protein secretory leukocyte protease inhibitor. We demonstrate here by culturing mouse tracheal epithelial cells at an air-liquid interface that, despite the production of Defb1, Defb14, and Defr1 in this system, these cells are unable to clear S. aureus when exposed to this respiratory pathogen. Using an adenovirus (Ad)-mediated gene transfer strategy, we show that overexpression of elafin, an anti-elastase/antimicrobial molecule (also a member of the four-disulfide core protein family), dramatically improves the clearance of S. aureus. In addition, we also demonstrate that this overexpression is efficient in vivo and that intratracheal instillation of Ad-elafin significantly reduced the lung bacterial load and demonstrates concomitant anti-inflammatory activity by reducing neutrophil numbers and markers of lung inflammation, such as bronchoalveolar lavage levels of tumor necrosis factor and myeloperoxidase. These findings show that an increased antimicrobial activity phenotype is provided by the elafin molecule and have implications for its use in S. aureus-associated local and systemic infections.
机译：金黄色葡萄球菌是一种常见于肺炎和败血症的病原体。在这种生物体对常规抗生素具有抗性的背景下，对天然内源性抗菌分子的调控的理解至关重要。先前的研究表明，人和小鼠的呼吸道都表达多种这些分子，包括防御素，cathelicidins和四硫键核心蛋白分泌型白细胞蛋白酶抑制剂。我们通过在气液界面上培养小鼠气管上皮细胞来证明这一点，尽管在此过程中产生了 Defb1 ， Defb14 和 Defr1 系统中，这些单元格无法清除 S。暴露于这种呼吸道病原体时会出现金黄色。使用腺病毒（Ad）介导的基因转移策略，我们显示抗弹性蛋白酶/抗微生物分子elafin（也是四-二硫键核心蛋白家族的成员）的过表达极大地提高了 S的清除率。金黄色。此外，我们还证明了这种过表达在体内是有效的，并且气管内滴注Ad-elafin可以显着降低肺部细菌负荷，并通过减少中性粒细胞数量和肺部炎症标志物（例如支气管肺泡灌洗液的水平）来显示伴随的抗炎活性。肿瘤坏死因子和髓过氧化物酶。这些发现表明，弹性蛋白分子提供了增强的抗菌活性表型，并对其在 S中的应用产生了影响。金黄色相关的局部和全身感染。

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