456 - Glutathione Deficiency and Neutrophil-Mediated Oxidative Stress in the Lungs of Young Children with Cystic Fibrosis

https://doi.org/10.1016/j.freeradbiomed.2016.10.519Get rights and content

Background

Despite limited evidence from studies in humans, the concentration of the antioxidant glutathione is widely considered to be low in the epithelial lining fluid (ELF) from patients with cystic fibrosis (CF) and extensive therapeutic efforts are put into restoring glutathione levels. However, to date it remains unclear, whether glutathione deficiency is an inherent defect in CF that occurs early in life, whether depletion of reduced glutathione is caused by neutrophil-mediated oxidative stress in the airways, and whether low glutathione is associated with bronchiectasis.

Methods

Using LC/MS, we measured glutathione (GSH), oxidized glutathione (GSSG), glutathione attached to proteins (GSSP) and glutathione sulfonamide (GSA) in BAL from 586 infants and children with CF and 63 without (ages 0.2-15.5 yr.). Levels of glutathione species were related to infection status, bronchiectasis data from chest computed tomography (CT) scans, markers of neutrophilic inflammation, neutrophil elastase (NE) and Il-8; and neutrophil-mediated oxidative stress, myeloperoxidase (MPO) and oxidized uric acid (allantoin).

Results

Glutathione levels were low in the lungs of individuals with CF from an early age irrespective of oxidation. GSH was decreased in children with infections; while oxidized glutathione species were elevated and related to other markers of neutrophil-related inflammation and oxidative stress. GSSP, MPO and NE, but not GSH, GSSG and GSA, were associated with bronchiectasis.

Conclusions

Airway glutathione is low in cystic fibrosis from a young age while marked neutrophil-mediated oxidation is present in the lung. Neutrophils promote a worse disease outcome both via oxidative modification of proteins and the release of NE highlighting the need to target both NE and MPO. At the same time, more research is needed into effective delivery of glutathione to sites of inflammation at a young age.

References (0)

Cited by (0)

View full text