Neutrophil elastase: alpha-1-proteinase inhibitor complex in serum and bronchoalveolar lavage fluid in patients with pulmonary fibrosis

Abstract

It was hypothesized that neutrophil elastase released from activated neutrophils may play an important role in the pathogenesis of pulmonary fibrosis. In the present study, we measured the neutrophil elastase:alpha-1-proteinase inhibitor complex (E-PI) in serum and bronchoalveolar lavage fluid (BALF) in 26 patients with pulmonary fibrosis and evaluated the correlation between E-PI levels and several parameters. E-PI levels in serum of patients with pulmonary fibrosis (635.8+/-112.0 ng.mL(-1)) were significantly elevated compared to normal nonsmokers (122.0+/-4.0 ng.mL(-1)) as well as normal smokers (132.8+/-8.4 ng.mL(-1)) (p<0.01). E-PI levels in serum significantly correlated with hepatocyte growth factor (HGF) levels in serum, C-reactive protein (CRP), and negatively correlated with arterial oxygen tension (Pa,O2), and arterial carbon dioxide tension (Pa,CO2). E-PI/albumin levels in BALF significantly correlated with HGF/albumin levels in BALF, lactate dehydrogenase (LDH)/albumin in BALF, total number of inflammatory cells (alveolar macrophages and neutrophils) in BALF, and several markers derived from epithelial cells in BALF. Our data demonstrated: 1) neutrophil elastase:alpha-1-proteinase inhibitor complex in serum increased in patients with pulmonary fibrosis; and 2) neutrophil elastase:alpha-1-proteinase inhibitor complex in serum and bronchoalveolar lavage fluid correlated with clinical parameters in pulmonary fibrosis. These results suggest that neutrophil elastase may play a significant role in the process of lung injury in pulmonary fibrosis.

Overexpression of α1-protease Inhibitor and Galectin-1 in Radiation-induced Early Phase of Pulmonary Fibrosis

“…The number of proteins identified in this study was much less than expected compared with other reports dealing with pulmonary diseases using immunohistochemistry (24,25), which might have been due to the time point in starting the experiment after irradiation. RIF might not have been fully developed.…”

“…However, they failed to provide direct evidence of α1-protease inhibitor expression. The formation of α1-protease inhibitor complex was confirmed in the lung parenchyma as well as in the BAL fluid and serum from idiopathic pulmonary fibrosis (IPF) patients (24,25). This strengthens the value of the α1-protease inhibitor as a disease marker, showing high levels of neutrophil elastase.…”

“…An increase in polymorphnuclear neutrophils in the brochoalveolar lavage (BAL) fluid, neutrophil infiltration and neutrophilc alveolitis in the lung tissues have frequently been observed in various pulmonary diseases, including belomycin and radiation-induced pulmonary fibrosis (22,23). Neutrophil elastase, which is a powerful proteinase released by neutrophils, destroys the extracellular matrix, modifies the airway epithelial cells and interferes with the respiratory host defense mechanisms (24). In vivo, neutrophil elastase is normally regulated by serum antiproteinase, the α1-protease inhibitor, which inactivates the free enzyme by rapidly forming complexes with it (25).…”

Validation of assays for inflammatory mediators in sputum

“…In recent years, there has been increasing interest in the role of lung inflammation in the development and progression of a variety of lung diseases as diverse as pulmonary fibrosis [1], cystic fibrosis [2], idiopathic bronchiectasis [3], chronic obstructive pulmonary disease (COPD) [4] and asthma [5]. These studies have been facilitated by the widespread availability of commercial assays to measure the inflammatory mediators of interest.…”

A neutrophil elastase inhibitor prevents bleomycin-induced pulmonary fibrosis in mice

“…NE induces lung epithelial apoptosis via proteinase-activated receptor (PAR)-1 [14], and PAR-1 could play an important role in inflammatory and fibroproliferative responses in ALI/ARDS [10,15]. The serum NE level was elevated in patients with pulmonary fibrosis [16,17], and some evidence does suggest that inhibition of its activity could attenuate the development of the disease [13,18,19].…”