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Protein oxidation by chronic pulmonary diseases in children
1Lung Research Group, Children's Hospital, Ludwig Maximilians University, Munich, Germany.
Insights
Protein oxidation is elevated in children with chronic lung diseases, linked to neutrophilic inflammation and lung damage. This study quantifies oxidation in pediatric lung conditions, identifying key affected proteins.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Pediatric Pulmonology
Background:
- Protein oxidation is implicated in chronic inflammatory lung diseases and lung damage.
- The extent and protein distribution of oxidation in pediatric lung diseases are largely unknown.
Purpose of the Study:
- To assess protein oxidation levels and distribution in pediatric chronic lung diseases.
- To investigate the relationship between protein oxidation and neutrophilic inflammation.
Main Methods:
- Protein carbonyls were measured in bronchoalveolar lavages (BAL) from children.
- Dot-blot assay, 2D electrophoresis, and Western blotting were used to analyze oxidized proteins.
- Comparison was made between patients with chronic lung diseases and healthy controls.
Main Results:
- Significantly higher protein oxidation was found in patients with interstitial lung disease, gastro-esophageal reflux disease, and pulmonary alveolar proteinosis compared to controls.
- Serum albumin, surfactant protein A, and alpha1-antitrypsin were identified as the most oxidation-sensitive proteins.
- The degree of protein oxidation correlated positively with neutrophilic granulocyte counts in BAL fluid.
Conclusions:
- Children with chronic pulmonary diseases exhibit increased oxidative stress in their lungs.
- Neutrophilic inflammation, through reactive oxygen species, appears to be a key factor in pulmonary damage.
- Significant interindividual variations in protein oxidation highlight the complexity of these conditions.
Abstract:
The oxidation of proteins may play an important role in the pathogenesis of chronic inflammatory lung diseases, and may contribute to lung damage. However, the extent of oxidation and the distribution among proteins are not known for most pediatric lung diseases. In this work, protein oxidation was assessed as protein carbonyls. Bronchoalveolar lavages (BAL) from children with chronic lung diseases were investigated by dot-blot assay for content and for pattern of distribution of oxidized proteins by two-dimensional (2D) electrophoresis and Western blotting. Significantly higher levels of protein oxidation than in healthy controls were determined in groups of patients with interstitial lung disease, gastro-esophageal reflux disease, and pulmonary alveolar proteinosis. The proteins most sensitive to oxidation were serum albumin, surfactant protein A, and alpha1-antitrypsin. Our data show increased oxidative stress in lungs of children with chronic pulmonary diseases, with significant interindividual variations. The extent of protein oxidation was proportional to the count of neutrophilic granulocytes in BAL fluid. These findings strongly support the concept that an abundance of reactive oxygen species produced during neutrophilic inflammation may be a deleterious factor, leading to pulmonary damage in these patients.
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