Oxidative changes of bronchoalveolar proteins in cystic fibrosis.
Chronic bacterial infection and severe, polymorphonuclear neutrophil-dominated endobronchial inflammation are characteristic hallmarks of cystic fibrosis (CF) lung disease. The free radicals generated can be deleterious for structure and function of many proteins. The goal of this study was to investigate the degree of oxidation of pulmonary epithelial lining fluid proteins. BAL fluid (BALF) from 55 children with CF and from 11 patients in a control group were investigated by dot-blot assay for content and by two-dimensional electrophoresis and Western blotting for the pattern of distribution of oxidized proteins. The highest level of oxidative stress, as assessed by the level of protein carbonyls, was found in patients with FEV1 < 80% of predicted or with highly elevated neutrophil counts. Compared to control subjects without lung disease, CF patients with normal lung function and CF patients with a normal neutrophil count in their BALF had significantly higher protein carbonyl levels. The extent of protein oxidation was directly related to the neutrophil granulocyte count and inversely to lung function. Our data support the hypothesis that oxidative damage of pulmonary proteins during chronic and excessive neutrophilic endobronchial inflammation may contribute to the decline of lung function in CF patients.
Lung Research Group, Children's Hospital of Ludwig Maximilians University, Munich.
Vitaliy
V
Starosta
Department of Pediatric Pneumology and Allergology, Childrens' Hospital University of Cologne, Cologne.
Ernst
E
Rietschel
Department of Pediatric Pneumology and Immunology, Charité, Humboldt-University, Berlin.
Karl
K
Paul
Department of Pediatric Pulmonology and Neonatology, Hannover Medical School, Hannover, Germany.
Ulrich
U
Baumann
Lung Research Group, Children's Hospital of Ludwig Maximilians University, Munich. Electronic address: matthias.griese@med.uni-muenchen.de.
Matthias
M
Griese
D000293:Adolescent; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D004591:Electrophoresis, Polyacrylamide Gel; D005541:Forced Expiratory Volume; D006801:Humans; D015151:Immunoblotting; D008450:Maximal Midexpiratory Flow Rate; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D050050:Protein Carbonylation; D011506:Proteins / Q000378:metabolism*; D014797:Vital Capacity
D011506:Proteins