Levels of Components of the Urokinase-Type Plasminogen Activator System are Related to Chronic Obstructive Pulmonary Disease Parenchymal Destruction and Airway Remodelling

Abstract

Retrospective study to investigate levels of components of the urokinase-type plasminogen activator (uPA) system in patients with chronic obstructive pulmonary disease (COPD). Peripheral lung tissue was obtained from patients who underwent surgical resection for benign lung diseases: 16 patients with COPD, 10 controls without lung function impairment who were smokers, and 10 controls without lung function impairment who were nonsmokers. Immunohistochemical staining for uPA, uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) was quantified. Airway remodelling (collagen; detected by Sirius red staining), lung function (determined by spirometry) and emphysema (alveolar destruction; percentage of low attenuation areas on computed tomography scan) were evaluated. uPA, uPAR and PAI-1 were significantly different in structural lung cells and pulmonary macrophages from patients with COPD compared with controls. There were significant positive correlations between collagen levels and uPA and PAI-1, and between uPA and degree of emphysema. There were significant inverse correlations between lung function and uPA, uPAR and PAI-1. Correlations between components of the uPA system and lung function, small airway fibrosis and emphysema indicate a role for the uPA system in COPD.