BACKGROUND: Matrix metalloproteinases (MMPs) are involved in the remodelling and degradation of extracellular matrix and may play a role in pulmonary tissue destruction in cystic fibrosis (CF). METHODS: Bronchoalveolar lavage (BAL) fluid levels of MMP-8, MMP-9, and their natural inhibitor TIMP-1 were measured on two occasions within 18 months in 23 children with mild CF, 13 of whom were treated with DNase. RESULTS: MMP-8 (39.3 (6.8) v 0.12 (0.01) ng/ml), MMP-9 (58.0 (11.4) v 0.5 (0.02) ng/ml), and the molar ratio of MMP-9/TIMP-1 (0.36 (0.05) v 0.048 (0.01)) were significantly higher in patients with CF than in control children without lung disease. Gelatine zymography showed the typical banding pattern of neutrophil derived MMP-9, including 130 kDa NGAL-MMP-9 complex and 92 kDa latent MMP-9 bands; 85 kDa bands (corresponding to active MMP-9) were seen in all patients. There was a close correlation between BAL fluid concentrations of MMPs and alpha(2)-macroglobulin, a marker of alveolocapillary leakage. After 18 months MMP levels were increased in untreated patients and decreased in patients treated with DNase. CONCLUSIONS: Uninhibited MMPs may contribute to pulmonary tissue destruction even in CF patients with mild lung disease that may be positively affected by treatment with DNase.
BACKGROUND: Matrix metalloproteinases (MMPs) are involved in the remodelling and degradation of extracellular matrix and may play a role in pulmonary tissue destruction in cystic fibrosis (CF). METHODS: Bronchoalveolar lavage (BAL) fluid levels of MMP-8, MMP-9, and their natural inhibitor TIMP-1 were measured on two occasions within 18 months in 23 children with mild CF, 13 of whom were treated with DNase. RESULTS:MMP-8 (39.3 (6.8) v 0.12 (0.01) ng/ml), MMP-9 (58.0 (11.4) v 0.5 (0.02) ng/ml), and the molar ratio of MMP-9/TIMP-1 (0.36 (0.05) v 0.048 (0.01)) were significantly higher in patients with CF than in control children without lung disease. Gelatine zymography showed the typical banding pattern of neutrophil derived MMP-9, including 130 kDa NGAL-MMP-9 complex and 92 kDa latent MMP-9 bands; 85 kDa bands (corresponding to active MMP-9) were seen in all patients. There was a close correlation between BAL fluid concentrations of MMPs and alpha(2)-macroglobulin, a marker of alveolocapillary leakage. After 18 months MMP levels were increased in untreated patients and decreased in patients treated with DNase. CONCLUSIONS: Uninhibited MMPs may contribute to pulmonary tissue destruction even in CFpatients with mild lung disease that may be positively affected by treatment with DNase.
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