[Higher levels of urokinase plasminogen activator system components in the airways of chronic obstructive pulmonary disease patients].Zhonghua Jie He He Hu Xi Za Zhi. 2006 Nov; 29(11):723-6.ZJ
To investigate the state and the pathophysiologic significances of urinary plasminogen activator system components in airways of patients with chronic obstructive pulmonary disease (COPD).
(1) Assay of induced sputum: 56 patients with COPD in stable clinical conditions (COPD group), aged (51 +/- 11) years with forced expiratory volume in one second of predicted % (FEV1% predicted) (53.5 +/- 14.4)% predicted, and 26 healthy control subjects (control group), aged (46 +/- 9) years; FEV1% predicted (85.1 +/- 1.0)% were studied. Levels of urokinase plasminogen activator system components in induced sputum, urokinase plasminogen activator (u-PA), urokinase plasminogen activator receptor (u-PAR), plasminogen activator inhibitor-1 (PAI-1) and interleukin-8 (IL-8), interferon-gamma (IFN-gamma), tumor necrosis factor (TNF-alpha), and interleukin-10 (IL-10) were determined by enzyme linked immunosorbent assay. (2) Pathological section of resected lung tissue: The study subjects included 11 patients receiving lung lobectomy for COPD with emphysematous bullae, aged (53 +/- 7) years, FEV1% predicted (58.3 +/- 6.6)%; as well as 10 non-COPD patients receiving lung lobectomy for local lesions with normal lung function, aged (47 +/- 12) years, FEV1% predicted (84.3 +/- 1.6)%, of which 3 were inflammatory pseudotumor, 5 were hamartoma, and 2 tuberculoma as the control. Cell expression of u-PA, u-PAR, PAI-1 in the pulmonary pathologic sections was investigated by immunohistochemistry.
Induced sputum of COPD patients showed significant increase in u-PAR, PAI-1, and IL-8 compared to the control subjects, (570 +/- 614) ng/L vs (97 +/- 74) ng/L (t = 5.629, P < 0.01), (6162 +/- 9247) ng/L vs (574 +/- 731) ng/L (t = 4.346, P < 0.01) and (12,370 +/- 17,292) ng/L vs (1868 +/- 1905) ng/L (t = 4.486, all P < 0.01); and there were no differences in u-PA, IFN-gamma, TNF-alpha, and IL-10. Correlation analysis showed that u-PAR and PAI were positively correlated with IL-8 in COPD patients (r = 0.483, 0.770, all P < 0.01), while PAI negatively correlated with FEV1% (r = -0.272, P < 0.05). No correlation was found in healthy control subjects. u-PAR was localized in alveolar epithelial cells, macrophages, neutrophils and lymphocytes in COPD subjects, while u-PAR was mainly localized in alveolar epithelial cells in the control subjects. The ratio of positive expression in alveolar epithelial cells of control subjects was significantly lower than in that of COPD subjects (33 +/- 18)% vs (49 +/- 16)% (t = 2.213, P < 0.05), while the detectable intensity of expression in these cells of control subjects was also weaker than that of COPD subjects. PAI-1 was localized in fibroblasts, macrophages and neutrophils in COPD subjects, while mainly localized in fibroblasts in control subjects; the ratio of positive expression in fibroblasts in control subjects was also significantly lower than that in COPD subjects (37 +/- 16)% vs (61 +/- 16)% (t = 3.419, P < 0.05), meanwhile the detectable intensity of expression in these cells of control subjects was weaker than that of COPD one.
u-PA system components are important inflammatory mediators in airways of COPD. PAI-1 is most likely to play a significant role in airway remodelling of COPD.