Drannik Anna G, Pouladi Mahmoud A, Robbins Clinton S, Goncharova Susanna I, Kianpour Sussan, Stämpfli Martin R
McMaster University, Department of Pathology and Molecular Medicine, Health Sciences Centre, Room 4H21A, 1200 Main Street West, Hamilton, ON, L8N 3Z5 Canada.
Am J Respir Crit Care Med. 2004 Dec 1;170(11):1164-71. doi: 10.1164/rccm.200311-1521OC. Epub 2004 Aug 18.
The object of this study was to investigate the impact of cigarette smoke on bacterial clearance and immune inflammatory parameters after infection with Pseudomonas aeruginosa in mice. We observed a delayed rate of bacterial clearance in smoke-exposed compared with sham-exposed mice. This was associated with increased inflammation characterized by greater numbers of neutrophils and mononuclear cells in the bronchoalveolar lavage. After infection, we observed increased levels of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) and chemokines (monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-2 [MIP-2]) as well as myeloperoxidase and proteolytic activity in the lungs of smoke-exposed compared with sham-exposed animals. Delayed clearance was associated with increased morbidity and greater weight loss of smoke-exposed mice. After delivery of inactivated bacteria, we observed a similar inflammatory response, clinical score, and tumor necrosis factor-alpha expression in smoke- and sham-exposed animals, suggesting that increased inflammation and altered clinical presentation are due to the delayed rate of bacterial clearance. Our findings suggest that cigarette smoke affects respiratory immune-inflammatory responses elicited by bacteria. We postulate that altered respiratory host defense may be implicated in smoking-related diseases such as chronic obstructive pulmonary disease.
本研究的目的是调查香烟烟雾对小鼠感染铜绿假单胞菌后细菌清除及免疫炎症参数的影响。我们观察到，与假暴露小鼠相比，烟雾暴露小鼠的细菌清除率延迟。这与炎症增加有关，其特征为支气管肺泡灌洗中中性粒细胞和单核细胞数量增多。感染后，与假暴露动物相比，我们观察到烟雾暴露动物肺中促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6）、趋化因子（单核细胞趋化蛋白-1 [MCP-1] 和巨噬细胞炎性蛋白-2 [MIP-2]）以及髓过氧化物酶和蛋白水解活性水平升高。清除延迟与烟雾暴露小鼠发病率增加和体重减轻更多有关。在给予灭活细菌后，我们在烟雾暴露和假暴露动物中观察到类似的炎症反应、临床评分和肿瘤坏死因子-α表达，这表明炎症增加和临床表现改变是由于细菌清除率延迟所致。我们的研究结果表明，香烟烟雾会影响细菌引发的呼吸道免疫炎症反应。我们推测，呼吸道宿主防御改变可能与慢性阻塞性肺疾病等吸烟相关疾病有关。
