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Matrix metalloproteases in BAL fluid of patients with cystic fibrosis and their modulation by treatment with dornase alpha
  1. F Ratjen1,
  2. C-M Hartog2,
  3. K Paul3,
  4. J Wermelt2,
  5. J Braun2
  1. 1Children’s Hospital, University of Essen, D-45122 Essen, Germany
  2. 2Department of Medicine II, Medical University of Lubeck, D-23538 Lubeck, Germany
  3. 3Department of Pediatrics, Charité Campus Virchow, University Hospital of Humboldt University, D-13353 Berlin, Germany
  1. Correspondence to:
    Dr F Ratjen, Children’s Hospital, University of Essen, Hufelandstrasse 55, D-45122 Essen, Germany;


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 α2-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.

  • bronchoalveolar lavage
  • cystic fibrosis
  • metalloprotease
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  • The study was in part supported by the German CF Foundation and Roche, Germany.

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