Herr Christian, Han Gang, Li Dong, Tschernig Thomas, Dinh Quoc Thai, Beißwenger Christoph, Bals Robert
Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany.
Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany.
Exp Toxicol Pathol. 2015 Mar;67(3):261-9. doi: 10.1016/j.etp.2015.01.002. Epub 2015 Jan 16.
Abundant microbial colonization is a hallmark of COPD and smoke exposure likely increases the susceptibility to colonization and infection. The aim of the present study was to characterize the pulmonary changes of a combined exposure to cigarette smoke (CS) and microbial challenge in a preclinical murine COPD model. Animals were exposed to CS for 2 weeks, 3, and 6 months. Low and high doses of heat inactivated nontypeable Haemophilus influenzae (NTHi) were administered by inhalation during the whole exposure time. Pulmonary changes were analyzed by stereology, pulmonary function tests, measurements of inflammatory cells and mediators, and histopathology. Exposure of smoke in a relatively low concentration caused COPD-like changes of pulmonary function and only little inflammation. The coadministration of low dose NTHi (ld-NTHi) augmented a macrophage dominated inflammatory profile, while high dose NTHi (hd-NTHi) induced a neutrophilic inflammatory pattern. IL-17A secretion was solely dependent on the exposure to NTHi. Also goblet cell metaplasia and the formation of lymphoid aggregates depended on exposure to bacteria. In conclusion, the combination of exposure to smoke and bacterial compounds resulted in a mouse model that resembles several aspects of human disease. Exposure to microbial structural components appears necessary to model important pathologic features of the disease and the quantity of the exposure with microorganisms has a strong effect on the phenotype.
丰富的微生物定植是慢性阻塞性肺疾病（COPD）的一个标志，而接触烟雾可能会增加对定植和感染的易感性。本研究的目的是在临床前小鼠COPD模型中，描述联合暴露于香烟烟雾（CS）和微生物刺激后的肺部变化。将动物暴露于CS中2周、3个月和6个月。在整个暴露期间，通过吸入给予低剂量和高剂量的热灭活不可分型流感嗜血杆菌（NTHi）。通过体视学、肺功能测试、炎症细胞和介质的测量以及组织病理学分析肺部变化。暴露于相对低浓度的烟雾会引起类似COPD的肺功能变化且仅有轻微炎症。联合给予低剂量NTHi（ld-NTHi）会增强以巨噬细胞为主的炎症特征，而高剂量NTHi（hd-NTHi）则诱导中性粒细胞炎症模式。白细胞介素-17A（IL-17A）的分泌仅取决于对NTHi的暴露。杯状细胞化生和淋巴样聚集物的形成也取决于对细菌的暴露。总之，暴露于烟雾和细菌成分的组合产生了一个类似于人类疾病多个方面的小鼠模型。暴露于微生物结构成分似乎是模拟该疾病重要病理特征所必需的，并且与微生物的暴露量对表型有强烈影响。
