Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema

Evidence for the contribution of neutrophils to the pathogenesis of pulmona ry emphysema is not convincing. We evaluated neutrophil involvement in subc linical pulmonary emphysema by measuring human neutrophil lipocalin (HNL) a nd two matrix metalloproteinases, gelatinase B (MMP-9) and neutrophil colla genase (MMP-8), in bronchoalveolar ravage fluid (BALF) from 65 community-ba sed older volunteers. HNL is a recently isolated 24-kD protein secreted fro m secondary granules of activated neutrophils. Despite no appreciable incre ase in the number of neutrophils, the level of HNL was significantly increa sed in BALF from subjects with emphysema evidenced by computed tomography r egardless of current smoking, as compared with smokers without emphysema. T he levels of MMP-9 and MMP-8 were also significantly higher in current smok ers with emphysema than in those without emphysema. The appearance of a 130 -kD HNL/MMP-9 complex on gelatin zymography and HNL immunoblot indicated ne utrophils to be a significant source of MMP-9 in the subjects' BALF. In a 2 4-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 gr oups. These data provide further evidence for neutrophil involvement in sub clinical pulmonary emphysema.