Julia Hentschel1, Nele Fischer2, Wibke K Janhsen2, Udo R Markert3, Thomas Lehmann4, Jürgen Sonnemann5, Klas Böer6, Wolfgang Pfister7, Uta-Christina Hipler8, Jochen G Mainz2. 1. CF Centre, Department of Paediatrics, Jena University Hospital, Jena, Germany. Electronic address: Julia.Hentschel@med.uni-jena.de. 2. CF Centre, Department of Paediatrics, Jena University Hospital, Jena, Germany. 3. Department of Obstetrics, Jena University Hospital, Jena, Germany. 4. Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Germany. 5. Department of Paediatric Haematology and Oncology, Jena University Hospital, Jena, Germany. 6. Institute for Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Jena, Germany. 7. Institute of Medical Microbiology, Jena University Hospital, Jena, Germany. 8. Department of Dermatology, Jena University Hospital, Jena, Germany.
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. DISCUSSION: 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.
BACKGROUND: Balanced levels of proteases and anti-proteases are essential in host defense systems. In CFpatients' 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 CFpatients. 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. DISCUSSION: 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.
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