Fischer Katja, Doehn Jan-Moritz, Herr Christian, Lachner Carolin, Heinrich Annina, Kershaw Olivia, Voss Meike, Jacobson Max H, Gruber Achim D, Clauss Matthias, Witzenrath Martin, Bals Robert, Gutbier Birgitt, Slevogt Hortense
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
Septomics Research Center, Jena University Hospital, Jena, Germany.
Eur J Microbiol Immunol (Bp). 2018 Dec 11;8(4):128-134. doi: 10.1556/1886.2018.00019. eCollection 2018 Dec 23.
In chronic obstructive pulmonary disease (COPD), acute exacerbations and emphysema development are characteristics for disease pathology. COPD is complicated by infectious exacerbations with acute worsening of respiratory symptoms with as one of the most frequent pathogens. Although cigarette smoke (CS) is the primary risk factor, additional molecular mechanisms for emphysema development induced by bacterial infections are incompletely understood. We investigated the impact of on emphysema development in CS exposed mice and asked whether an additional infection would induce a solubilization of pro-apoptotic and pro-inflammatory endothelial monocyte-activating-protein-2 (EMAPII) to exert its activities in the pulmonary microvas-culature and other parts of the lungs not exposed directly to CS. Mice were exposed to smoke (6 or 9 months) and/or infected with Lungs, bronchoalveolar lavage fluid (BALF), and plasma were analyzed. CS exposure reduced ciliated area, caused rarefaction of the lungs, and induced apoptosis. EMAPII was increased independent of prior smoke exposure in BALF of infected mice. Importantly, acute infection increased release of matrixmetalloproteases-9 and -12, which are involved in emphysema development and comprise a mechanism of EMAPII release. Our data suggest that acute infection represents an independent risk factor for emphysema development in smoke-exposed mice.
在慢性阻塞性肺疾病（COPD）中，急性加重和肺气肿形成是疾病病理的特征。COPD常并发感染性加重，导致呼吸道症状急性恶化， 是最常见的病原体之一。虽然香烟烟雾（CS）是主要危险因素，但细菌感染诱发肺气肿形成的其他分子机制尚不完全清楚。我们研究了 在暴露于CS的小鼠中对肺气肿形成的影响，并探讨额外感染是否会诱导促凋亡和促炎的内皮单核细胞激活蛋白-2（EMAPII）溶解，从而在肺微血管和未直接暴露于CS的肺其他部位发挥其作用。将小鼠暴露于烟雾中（6或9个月）和/或感染 ，对肺、支气管肺泡灌洗液（BALF）和血浆进行分析。CS暴露减少了纤毛面积，导致肺组织稀疏，并诱导细胞凋亡。在感染小鼠的BALF中，EMAPII的增加与先前是否暴露于烟雾无关。重要的是，急性 感染增加了基质金属蛋白酶-9和-12的释放，这两种酶参与肺气肿形成，也是EMAPII释放的一种机制。我们的数据表明，急性 感染是暴露于烟雾的小鼠发生肺气肿的独立危险因素。
