Related Experiment Videos
Myeloperoxidase and protein oxidation in cystic fibrosis
A Van Der Vliet1, M N Nguyen, M K Shigenaga
1Division of Pulmonary/Critical Care Medicine, Department of Internal Medicine, University of California, Davis, California 95616, USA. avandervliet@ucdavis.edu
Abstract:
Cystic fibrosis (CF) is associated with chronic pulmonary inflammation and progressive lung dysfunction, possibly associated with the formation of neutrophil myeloperoxidase (MPO)-derived oxidants. Expectorated sputum specimens from adult CF patients were analyzed for MPO characteristic protein modifications and found to contain large amounts of active MPO as well as high levels of protein-associated 3-chlorotyrosine and 3,3'-dityrosine, products that result from MPO activity, compared with expectorated sputum from non-CF subjects. Sputum levels of nitrite (NO(2)(-)) and nitrate (NO(3)(-)), indicating local production of nitric oxide (NO. ), were not elevated but in fact were slightly reduced in CF. However, there was a slight increase in protein-associated 3-nitrotyrosine in CF sputum compared with controls, reflecting the formation of reactive nitrogen intermediates, possibly through MPO-catalyzed oxidation of NO(2)(-). CF sputum MPO was found to contribute to oxidant-mediated cytotoxicity toward cultured tracheobronchial epithelial cells; however, peroxidase-dependent protein oxidation occurred primarily within sputum proteins, suggesting scavenging of MPO-derived oxidants by CF mucus and perhaps formation of secondary cytotoxic products within CF sputum. Our findings demonstrate the formation of MPO-derived oxidizing and possibly nitrating species within the respiratory tract of subjects with CF, which collectively may contribute to bronchial injury and respiratory failure in CF.
Insights
Cystic fibrosis (CF) patients have increased myeloperoxidase (MPO) activity in their lungs, leading to harmful oxidants. This MPO activity contributes to lung injury and dysfunction in CF patients.
Area of Science:
- Biochemistry
- Pulmonology
- Cell Biology
Background:
- Cystic fibrosis (CF) involves chronic lung inflammation and dysfunction.
- Neutrophil myeloperoxidase (MPO)-derived oxidants may contribute to CF lung pathology.
- Understanding MPO's role in CF is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the presence and activity of MPO and its products in CF sputum.
- To determine the contribution of MPO to cytotoxicity in CF airways.
- To elucidate the role of MPO-derived oxidants and nitrogen species in CF pathogenesis.
Main Methods:
- Analysis of expectorated sputum from adult CF patients and non-CF controls.
- Quantification of active MPO, 3-chlorotyrosine, 3,3'-dityrosine, nitrite, nitrate, and 3-nitrotyrosine.
- Assessment of MPO-mediated cytotoxicity on cultured tracheobronchial epithelial cells.
Main Results:
- CF sputum showed significantly higher levels of active MPO, 3-chlorotyrosine, and 3,3'-dityrosine compared to controls.
- Nitrite and nitrate levels were not elevated, but 3-nitrotyrosine was slightly increased in CF sputum.
- CF sputum MPO induced cytotoxicity in epithelial cells, with oxidation primarily occurring within sputum proteins.
Conclusions:
- MPO-derived oxidizing and nitrating species are formed in the CF respiratory tract.
- These MPO products may contribute to bronchial injury and respiratory failure in CF.
- CF mucus may scavenge MPO-derived oxidants, potentially forming secondary cytotoxic products.