MMP-2-and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease

Background: The course of asthma and chronic obstructive pulmonary disease (COPD) is associated with bronchial morphological changes. Metalloproteinas es are thought to play a role in these structural changes. Methods: We stud ied the gelatinolytic activity present in the induced sputum from 20 patien ts with asthma, 20 with COPD and 19 healthy controls. The assessment of gel atinolytic activity was performed by quantitative zymography, and gelatinol ytic species were identified by Western blot analysis. Tissue inhibitor of metalloproteinase-l (TIMP-1) was detected by reverse zymography and ELISA. Results: From zymography, we found significantly higher gelatinolytic activ ity linked to pro-matrix metalloproteinase-9 (pro-MMP-9) in the sputum from asthmatics (p < 0.0001) and COPD patients (p < 0.0001) compared to the con trol group. Furthermore, the activated form of MMP-9 (85 kD) was found in t he sputum from 60% of asthmatics and 85% of COPD patients, but was absent i n that of control subjects (p < 0.0001). Importantly, although less frequen tly detectable than pro-MMP-9, pro-MMP-2 (72 kD) was found more frequently in asthmatics (50%) than in control subjects (5%) (p < 0.005). We also desc ribed two unusual gelatinolytic species of 45 and 120 kD and showed that th ey derived from MMP-9 according to their ability to bind gelatin and anti-M MP-9 antibody. Levels of TIMP-1 were higher in asthmatics (p < 0.05) and CO PD patients (p < 0.05) than in controls. Conclusion: Asthmatics and COPD pa tients display an increased gelatinolytic activity linked to MMP-2 and MMP- 9 and higher levels of TIMP-1 in their sputum. Copyright (C) 2000 S. Karger AG, Basel.