Center for Health and the Environment, University of California Davis, Davis, California, United States of America.
PLoS One. 2012;7(3):e33304. doi: 10.1371/journal.pone.0033304. Epub 2012 Mar 21.
Chronic obstructive pulmonary disease (COPD) kills approximately 2.8 million people each year, and more than 80% of COPD cases can be attributed to smoking. Leukocytes recruited to the lung contribute to COPD pathology by releasing reactive oxygen metabolites and proteolytic enzymes. In this work, we investigated where leukocytes enter the lung in the early stages of COPD in order to better understand their effect as a contributor to the development of COPD. We simultaneously evaluated the parenchyma and airways for neutrophil accumulation, as well as increases in the adhesion molecules and chemokines that cause leukocyte recruitment in the early stages of tobacco smoke induced lung disease. We found neutrophil accumulation and increased expression of adhesion molecules and chemokines in the bronchial blood vessels that correlated with the accumulation of leukocytes recovered from the lung. The expression of adhesion molecules and chemokines in other vascular beds did not correlate with leukocytes recovered in bronchoalveolar lavage fluid (BALF). These data strongly suggest leukocytes are recruited in large measure through the bronchial circulation in response to tobacco smoke. Our findings have important implications for understanding the etiology of COPD and suggest that pharmaceuticals designed to reduce leukocyte recruitment through the bronchial circulation may be a potential therapy to treat COPD.
慢性阻塞性肺疾病（COPD）每年导致约 280 万人死亡，其中 80%以上的 COPD 病例可归因于吸烟。浸润到肺部的白细胞通过释放活性氧代谢物和蛋白水解酶促进 COPD 发病机制。在这项工作中，我们研究了 COPD 早期白细胞进入肺部的部位，以便更好地了解它们作为 COPD 发展的促进因素的作用。我们同时评估了肺实质和气道中的中性粒细胞聚集情况，以及在吸烟引起的肺部疾病早期导致白细胞募集的粘附分子和趋化因子的增加情况。我们发现，支气管血管中的中性粒细胞聚集和粘附分子及趋化因子的表达增加，与从肺部回收的白细胞积累相关。其他血管床中粘附分子和趋化因子的表达与支气管肺泡灌洗液（BALF）中回收的白细胞没有相关性。这些数据强烈表明，白细胞在很大程度上是通过支气管循环募集的，以响应吸烟。我们的发现对理解 COPD 的病因学具有重要意义，并表明设计通过支气管循环减少白细胞募集的药物可能是治疗 COPD 的一种潜在疗法。
