Urokinase-type plasminogen activator system and human cationic antimicrobial protein 18 in serum and induced sputum of patients with chronic obstructive pulmonary disease

Background and objective: There is increasing evidence that the innate immune system plays an important role in the pathogenesis of COPD. The objective of this study was to quantify several innate immune biomarkers in serum and induced sputum of COPD patients, and healthy non-smokers and smokers. Methods: Serum and induced sputum levels of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), urokinase-type plasminogen activator inhibitor (PAI-1) and human cationic antimicrobial protein 18 (CAP18) were measured by ELISA, in 13 patients with stage I or stage II COPD (COPD I + II), 15 patients with stage III or stage IV COPD (COPD III + IV), 18 healthy non-smokers and 14 healthy smokers. In addition, membrane-bound uPAR in peripheral blood and induced sputum was assessed by flow cytometry. Results: Levels of uPAR, PAI-1 and CAP18 were elevated in induced sputum of COPD I + II and COPD III + IV patients, compared with healthy non-smokers (P < 0.05) and healthy smokers (P < 0.05). uPAR, PAI-1 and CAP18 levels were significantly higher in COPD III + IV patients compared with COPD I + II patients (P < 0.05). The expression of uPAR on induced sputum neutrophils and macrophages was significantly higher in COPD patients compared with healthy non-smokers (P < 0.05) and healthy smokers (P < 0.05). Sputum uPAR and CAP18 levels showed significant inverse correlations with FEV1% and 6MWD, and significant positive correlations with St. George's Respiratory Questionnaire scores. Conclusions: In COPD patients, increased induced sputum levels of uPAR, PAI-1 and CAP18 were associated with airflow limitation, health status and exercise tolerance, suggesting that these biomarkers may be implicated in the pathogenesis of COPD.