title: Matrix metalloproteases in BAL fluid of patients with cystic fibrosis and their modulation by treatment with dornase alpha.
abstract: 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.
authors.affiliation: Children's Hospital, University of Essen, D-45122 Essen, Germany. f.ratjen@uni-essen.de
authors.forename: F
authors.initials: F
authors.lastname: Ratjen
authors.forename: C-M
authors.initials: CM
authors.lastname: Hartog
authors.forename: K
authors.initials: K
authors.lastname: Paul
authors.forename: J
authors.initials: J
authors.lastname: Wermelt
authors.forename: J
authors.initials: J
authors.lastname: Braun
mesh_terms: D000293:Adolescent; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000201:enzymology*; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D000511:alpha-Macroglobulins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I; D007781:Lactoferrin; D018093:Gelatinases; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9