ROLE OF ALVEOLAR MACROPHAGES IN PATHOGENESIS OF PULMONARY EMPHYSEMA

肺泡巨噬细胞（AM）被认为参与肺气肿的发展。我们关注与AM相关的中性粒细胞弹性蛋白酶（NE）。本研究的目的是阐明NE在AM中的活性和释放能力，并研究其与肺气肿发生的可能关系。36名老年吸烟者和非吸烟者，他们都是社区志愿者，在CT扫描上评估了肺气肿变化的存在。对所有受试者进行支气管肺泡灌洗（BAL）以获得AM。CT扫描显示有肺气肿改变的吸烟者AM使用NE敏感底物（MEOSAAPVNA）的酯酶活性高于无肺气肿改变的吸烟者AM（p<0.05）。为了评价弹性蛋白酶与肺气肿发生的关系，我们采用ELISA法测定了39名老年志愿者支气管肺泡灌洗液中NE和组织蛋白酶B、L的含量，并以弹性蛋白降解肽（EDP）作为弹性蛋白过度降解的生化标志物。与非吸烟者相比，有肺气肿改变的吸烟者NE显著升高（P<0.01），与无肺气肿改变的吸烟者相比也显著升高（P<0.01）。组织蛋白酶B和L与吸烟状态或CT扫描上肺气肿改变的存在无关。吸烟者支气管肺泡灌洗液中EDP浓度显著高于非吸烟者（p<0.01），并与支气管肺泡灌洗液中NE-α 1-蛋白酶抑制剂复合物浓度显著相关（r=0.38，p<0.05）。

Alveolar macrophages (AMs) are thought to be involved in the development of pulmonary emphysems. We focused on neutrophil elastase (NE) associated with AMs. The purpose of this study was to elucidate the activity and releasability of NE in AMs, and to examine its possible relationship with the development of pulmonary emphysema. Thirty-six older smokers and nonsmorkers, who were all community volunteers, were evaluated for the presence of emphysematous changes on CT scans. Bronchoalveolar lavage (BAL) was performed to obtain AMs from all the subjects. Esterolytic activity using an NE-sensitive substrate (MEOSAAPVNA) was elevated in AMs from current smorkers with emphysematous changes on CT scans compared to those from current smorkers without emphysematous changes (p<0.05). We also demonstrated the accelerated releasability of NE from AMs in the subjects with emphysematous changes.To evaluate the linkage of elastases with development of pulmonary emphysema, we measured NE and Cathepsin B,L in BAL fluid from 39 older volunteers by ELISA and also elastin-degrated peptides (EDP) as a biochemical marker of excessive elastin degradation. NE was significantly elevated in smokers with emphysematous changes compared not only with nonsmokers (p<0.01), but also with current smokers without emphysematous changes (p<0.01). Cathepsin B and L were not related with smoking status or presence of emphysematous changes on CT scans. The concentration of EDP in BAL fluid was significantly higher in current smokers than noncurrent smokers (p<0.01) and was significantly related with NE-alpha1-proteinase inhibitor complex in BAL fluid (r=0.38, p<0.05).