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

Abstract

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.

Molecular composition of the alveolar lining fluid in the aging lung

“…Betsuyaku et al (1999) reported an . PC phosphatidylcholine, POPC 1-palmitoyl,2-oleoyl-sn-glycero-3-phosphocholine, DPPC 1,2-dipalmitoyl-sn-glycero-3-phosphocholine increase in neutrophils in human ALF as a marker of acute and/or chronic inflammation, i.e., from 2 % total neutrophils in ALF from healthy adults (mean age 28) to 8 % in ALF from idiopathic pulmonary fibrosis patients (mean age 58).…”

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

“…Whereas MMP-8 levels are significantly increased in BALF from patients with subclinical emphysema (Betsuyaku et al, 1999), levels of MMP-8 in the sputum of patients with emphysema correlate negatively with lung function if the patients have developed chronic obstructive pulmonary disease (COPD) (Culpitt et al, 2005). Finally, MMP-8 levels in BALF also correlate with the severity of bronchiectasis, a disease characterized by a permanent dilation of the bronchi due to chronic inflammation, leading to irreparable deformation of bronchial wall components (Sepper et al, 1995).…”

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

“…As compared with healthy subjects, patients with COPD have a marked increase in expression and activity of MMP-2, MMP-9 and MT1-MMP in their lung parenchyma (Ohnishi et al, 1998) and increased gelatinolytic activity linked to MMP-2 and MMP-9 in their sputum (Cataldo et al, 2000;Vignola et al, 1998b). In bronchoalveolar lavage fluid of smokers with emphysema, an increase of collagenolytic activity, probably due to elevated levels of MMP-8, is measured when compared to smokers without emphysema (Betsuyaku et al, 1999) indicating that injury to the collagen network of the lung is also a part of the disease. When studied ex vivo, alveolar macrophages from patients with emphysema express more MMP-1 and MMP-9 than macrophages from healthy subjects suggesting that macrophages are the main cellular source of MMP-1 and MMP-9 in COPD (Finlay et al, 1997a).…”