Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency
Neutrophil-derived myeloperoxidase (MPO) is recognized as a major source of oxidative stress at the airway surface of a cystic fibrosis (CF) lung where, despite limited evidence, the antioxidant glutathione is widely considered to be low. The aims of this study were to establish whether oxidative st...
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Veröffentlicht in: | Free radical biology & medicine 2017-12, Vol.113, p.236-243 |
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Zusammenfassung: | Neutrophil-derived myeloperoxidase (MPO) is recognized as a major source of oxidative stress at the airway surface of a cystic fibrosis (CF) lung where, despite limited evidence, the antioxidant glutathione is widely considered to be low. The aims of this study were to establish whether oxidative stress or glutathione status are associated with bronchiectasis and whether glutathione deficiency is inherently linked to CF or a consequence of oxidative stress.
MPO was measured by ELISA in 577 bronchoalveolar lavage samples from 205 clinically-phenotyped infants and children with CF and 58 children without CF (ages 0.2–6.92 years). Reduced glutathione (GSH), oxidized glutathione species (GSSG; glutathione attached to proteins, GSSP; glutathione sulfonamide, GSA) and allantoin, an oxidation product of uric acid, were measured by mass spectrometry.
The odds of having bronchiectasis were associated with MPO and GSSP. GSH was low in children with CF irrespective of oxidation. Oxidized glutathione species were significantly elevated in CF children with pulmonary infections compared to uninfected CF children. In non-CF children, infections had no effect on glutathione levels.
An inadequate antioxidant response to neutrophil-mediated oxidative stress during infections exists in CF due to an inherent glutathione deficiency. Effective delivery of glutathione and inhibition of MPO may slow the development of bronchiectasis.
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•Glutathione is low in cystic fibrosis (CF) bronchoalvealoar lavage fluid (BAL).•Glutathione deficiency occurs early in life and is not due to increased oxidation.•Protein glutathionylation (GSSP) correlates with neutrophil-derived oxidative stress.•Neutrophil myeloperoxidase and GSSP in BAL are associated with bronchiectasis.•GSH deficiency heightens, intensifies, amplifies oxidative stress during infections. |
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ISSN: | 0891-5849 1873-4596 |
DOI: | 10.1016/j.freeradbiomed.2017.09.028 |