Betsuyaku T, Nishimura M, Takeyabu K, Tanino M, Venge P, Xu S, Kawakami Y
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Am J Respir Crit Care Med. 1999 Jun;159(6):1985-91. doi: 10.1164/ajrccm.159.6.9809043.
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 lavage 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.
中性粒细胞在肺气肿发病机制中的作用证据并不确凿。我们通过检测65名社区老年志愿者支气管肺泡灌洗液（BALF）中的人中性粒细胞脂质运载蛋白（HNL）以及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），评估中性粒细胞在亚临床肺气肿中的参与情况。HNL是一种最近从活化中性粒细胞的次级颗粒中分离出的24 kDa蛋白质。尽管中性粒细胞数量没有明显增加，但与无肺气肿的吸烟者相比，通过计算机断层扫描证实有肺气肿的受试者的BALF中HNL水平显著升高，且与当前吸烟情况无关。有肺气肿的当前吸烟者的MMP - 9和MMP - 8水平也显著高于无肺气肿者。明胶酶谱和HNL免疫印迹上出现130 kDa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。在肺泡巨噬细胞的24小时培养基中，仅检测到MMP - 9的潜伏形式，且各组之间MMP - 9水平无差异。这些数据为中性粒细胞参与亚临床肺气肿提供了进一步证据。
