Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema
Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema
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DOI：
10.1164/ajrccm.159.6.9809043
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发表时间：
1999-06-01
影响因子：
24.7
通讯作者：
Kawakami, Y
中科院分区：
文献类型：
--
作者：
Betsuyaku, T;Nishimura, M;Kawakami, Y
关于中性粒细胞在肺气肿发病机制中的作用的证据并不令人信服。我们通过测量65名社区老年志愿者支气管肺泡破坏液（BALF）中的人中性粒细胞脂钙素（HNL）和两种基质金属蛋白酶，明胶酶B （MMP-9）和中性粒细胞胶原酶（MMP-8）来评估中性粒细胞在亚临床肺气肿中的作用。HNL是一种最近分离的24kd蛋白，由活化的中性粒细胞次级颗粒分泌。尽管中性粒细胞数量没有明显增加，但与没有肺气肿的吸烟者相比，计算机断层扫描显示，与吸烟与否无关，肺气肿患者的BALF中HNL水平显著增加。有肺气肿的吸烟者的MMP-9和MMP-8水平也明显高于没有肺气肿的吸烟者。明胶酶谱图和HNL免疫印迹显示，130-kD的HNL/MMP-9复合物表明中性粒细胞是受试者BALF中MMP-9的重要来源。在肺泡巨噬细胞培养液中，仅检测到MMP-9的潜伏形式，各组间MMP-9水平无差异。这些数据提供了中性粒细胞参与亚临床肺气肿的进一步证据。
Evidence for the contribution of neutrophils to the pathogenesis of pulmonary emphysema is not convincing. We evaluated neutrophil involvement in subclinical pulmonary emphysema by measuring human neutrophil lipocalin (HNL) and two matrix metalloproteinases, gelatinase B (MMP-9) and neutrophil collagenase (MMP-8), in bronchoalveolar ravage fluid (BALF) from 65 community-based older volunteers. HNL is a recently isolated 24-kD protein secreted from secondary granules of activated neutrophils. Despite no appreciable increase in the number of neutrophils, the level of HNL was significantly increased in BALF from subjects with emphysema evidenced by computed tomography regardless of current smoking, as compared with smokers without emphysema. The levels of MMP-9 and MMP-8 were also significantly higher in current smokers with emphysema than in those without emphysema. The appearance of a 130-kD HNL/MMP-9 complex on gelatin zymography and HNL immunoblot indicated neutrophils to be a significant source of MMP-9 in the subjects' BALF. In a 24-h culture medium of alveolar macrophages, only a latent form of MMP-9 was detected, and there was no difference in the level of MMP-9 between the groups. These data provide further evidence for neutrophil involvement in subclinical pulmonary emphysema.