title: Protease-antiprotease imbalances differ between Cystic Fibrosis patients' upper and lower airway secretions.
abstract: BACKGROUND
  Balanced levels of proteases and anti-proteases are essential in host defense systems. In CF patients' lungs, elevated protease/anti-protease-ratios contribute to damage of airway tissue and premature death with the inherited disease. Little is known about upper airway protease equilibrium in CF.
  
  
  METHODS
  Neutrophil elastase (NE), Secretory leukocyte protease inhibitor (SLPI), matrix metalloproteinase (MMP)9, tissue inhibitors of metalloproteinase (TIMP)1, cathepsin S (CTSS) and the corresponding cellular distribution were assessed in the nasal lavage (NL) and sputum of 40 CF patients.
  
  
  RESULTS
  Concentrations of all proteases and anti-proteases were markedly higher in sputum than in NL (NE: 10-fold, SLPI: 5000-fold). Interestingly, the NE/SLPI ratio was 726-fold higher in NL compared to sputum, while the MMP9/TIMP1 ratio was 4.5-fold higher in sputum compared to NL.
  
  
  CONCLUSIONS
  This first study to compare protease/anti-protease networks of CF upper and lower airways by NL and sputum reveals substantial differences between both compartments' immunological responses. This finding may have implications for sinonasal and pulmonary treatment, possibly leading to new therapeutic approaches.
authors.affiliation: CF Centre, Department of Paediatrics, Jena University Hospital, Jena, Germany. Electronic address: Julia.Hentschel@med.uni-jena.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Hentschel
authors.affiliation: CF Centre, Department of Paediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Nele
authors.initials: N
authors.lastname: Fischer
authors.affiliation: CF Centre, Department of Paediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Wibke K
authors.initials: WK
authors.lastname: Janhsen
authors.affiliation: Department of Obstetrics, Jena University Hospital, Jena, Germany.
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
authors.affiliation: Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehmann
authors.affiliation: Department of Paediatric Haematology and Oncology, Jena University Hospital, Jena, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Sonnemann
authors.affiliation: Institute for Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Jena, Germany.
authors.forename: Klas
authors.initials: K
authors.lastname: Böer
authors.affiliation: Institute of Medical Microbiology, Jena University Hospital, Jena, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pfister
authors.affiliation: Department of Dermatology, Jena University Hospital, Jena, Germany.
authors.forename: Uta-Christina
authors.initials: UC
authors.lastname: Hipler
authors.affiliation: CF Centre, Department of Paediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Jochen G
authors.initials: JG
authors.lastname: Mainz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D012137:Respiratory System / Q000201:enzymology* / Q000473:pathology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000378:metabolism*; D013183:Sputum / Q000166:cytology / Q000201:enzymology*; D055815:Young Adult
chemical_list: D053481:Secretory Leukocyte Peptidase Inhibitor; D019272:Leukocyte Elastase
keywords: Cathepsin; Lung; Nasal lavage; Neutrophil elastase; Protease; SLPI; Sinonasal