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Am. J. Respir. Crit. Care Med., Volume 159, Number 6, June 1999, 1985-1991

Neutrophil Granule Proteins in Bronchoalveolar Lavage Fluid from Subjects with Subclinical Emphysema

TOMOKO BETSUYAKU, MASAHARU NISHIMURA, KIMIHIRO TAKEYABU, MISHIE TANINO, PER VENGE, SHENGYUAN XU, and YOSHIKAZU KAWAKAMI

First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan; and Department of Clinical Chemistry, University Hospital, Uppsala, Sweden

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.




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