Centre for Respiratory Research, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, 5 University Street, London, UK.
Am J Respir Cell Mol Biol. 2012 Feb;46(2):180-7. doi: 10.1165/rcmb.2011-0182OC. Epub 2011 Sep 1.
Although empyema affects more than 65,000 people each year in the United States and in the United Kingdom, there are limited data on the pathogenesis of pleural infection. We investigated the pathogenesis of empyema using animal and cell culture models of Streptococcus pneumoniae infection. The pathological processes during the development of empyema associated with murine pneumonia due to S. pneumoniae (strain D39) were investigated. Lungs were examined using histology, and pleural fluid and blood bacterial colony-forming units, cytokine levels, and cellular infiltrate were determined over time. Bacterial migration across mesothelial monolayers was investigated using cell culture techniques, flow cytometry, and confocal microscopy. After intranasal inoculation with 10(7) S. pneumoniae D39 strain, mice developed pneumonia associated with rapid bacterial invasion of the pleural space; raised intrapleural IL-8, VEGF, MCP-1, and TNF-α levels; and caused significant intrapleural neutrophilia followed by the development of fibrinous pleural adhesions. Bacterial clearance from the pleural space was poor, and in vitro assays demonstrated that S. pneumoniae crossed mesothelial layers by translocation through cells rather than by a paracellular route. This study describes key events during the development of S. pneumoniae empyema using a novel murine model of pneumonia-associated empyema that closely mimics human disease. The model allows for future assessment of molecular mechanisms involved in the development of empyema and evaluation of potential new therapies. The data suggest that transmigration of bacteria through mesothelial cells could be important in empyema development. Furthermore, upon entry the pleural cavity offers a protected compartment for the bacteria.
尽管在美国和英国，每年有超过 65000 人患有脓胸，但关于胸膜感染的发病机制的数据有限。我们使用动物和细胞培养模型研究了肺炎链球菌感染的发病机制。研究了与肺炎链球菌（菌株 D39）引起的小鼠肺炎相关的脓胸发展过程中的病理过程。使用组织学检查肺部，并随时间推移确定胸腔液和血液中的细菌菌落形成单位、细胞因子水平和细胞浸润。使用细胞培养技术、流式细胞术和共聚焦显微镜研究了细菌穿过间皮单层的迁移。经鼻接种 107 肺炎链球菌 D39 株后，小鼠发生肺炎，胸膜空间迅速发生细菌入侵；胸腔内白细胞介素 8、血管内皮生长因子、单核细胞趋化蛋白 1 和肿瘤坏死因子-α 水平升高；并导致明显的胸腔内中性粒细胞增多，随后发生纤维性胸膜粘连。胸腔内的细菌清除不良，体外检测表明肺炎链球菌通过细胞内易位而不是通过细胞旁途径穿过间皮层。这项研究使用一种新型肺炎相关脓胸的小鼠模型描述了肺炎链球菌脓胸发展过程中的关键事件，该模型非常类似于人类疾病。该模型允许对脓胸发展中涉及的分子机制进行未来评估，并评估潜在的新疗法。数据表明，细菌穿过间皮细胞的迁移可能在脓胸发展中很重要。此外，进入胸腔后，细菌提供了一个受保护的隔室。
