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ROLE OF ALVEOLAR MACROPHAGES IN PATHOGENESIS OF PULMONARY EMPHYSEMA

肺泡巨噬细胞在肺气肿发病机制中的作用

基本信息

批准号：
05404031
负责人：
KAWAKAMI Yoshikazu
金额：
$ 10.5万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

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).

肺泡巨噬细胞（AM）被认为参与肺气肿的形成。我们重点关注与 AM 相关的中性粒细胞弹性蛋白酶 (NE)。本研究的目的是阐明 AMs 中 NE 的活性和释放性，并探讨其与肺气肿发生的可能关系。 36 名老年吸烟者和不吸烟者都是社区志愿者，他们接受了 CT 扫描是否存在肺气肿变化的评估。进行支气管肺泡灌洗（BAL）以获得所有受试者的 AM。与当前吸烟者无肺气肿变化的情况相比，在 CT 扫描中出现肺气肿变化的当前吸烟者的 AM 中，使用 NE 敏感底物 (MEOSAAPVNA) 的酯解活性升高 (p<0.05)。我们还证明了患有肺气肿变化的受试者中 AM 中 NE 的加速释放能力。为了评估弹性蛋白酶与肺气肿发展之间的联系，我们通过 ELISA 测量了 39 名老年志愿者的支气管肺泡灌洗液中的 NE 和组织蛋白酶 B、L，并使用弹性蛋白降解肽 (EDP) 作为弹性蛋白过度降解的生化标志物。与不吸烟者相比，有肺气肿改变的吸烟者的 NE 显着升高（p<0.01），而且与目前没有肺气肿改变的吸烟者相比也显着升高（p<0.01）。组织蛋白酶 B 和 L 与吸烟状况或 CT 扫描中是否存在肺气肿变化无关。当前吸烟者的 BAL 液中 EDP 浓度显着高于非当前吸烟者 (p<0.01)，并且与 BAL 液中的 NE-α1-蛋白酶抑制剂复合物显着相关 (r=0.38，p<0.05)。