Eosinophil peroxidase produces hypobromous acid in the airways of stable asthmatics.
Eosinophil peroxidase and myeloperoxidase use hydrogen peroxide to produce hypobromous acid and hypochlorous acid. These powerful oxidants may damage the lungs if they are produced as part of the inflammatory response in asthma. The aim of this study was to determine if peroxidases generate hypohalous acids in the airways of individuals with stable asthma, and if they affect lung function. Sputum was induced from patients with mild to moderate asthma and from healthy controls. Eosinophil peroxidase, myeloperoxidase, chlorinated and brominated tyrosyl residues, and protein carbonyls were measured in sputum supernatants. Eosinophil peroxidase protein was significantly elevated in asthmatic subjects whereas myeloperoxidase protein was not. There was significantly more 3-bromotyrosine (Br-Tyr) in proteins from the sputum of asthmatics compared to controls (0.79 vs. 0.23 mmol Br-Tyr/mol Tyr; medians p < .0001). Levels of 3-chlorotyrosine (0.23 vs. 0.14 mmol Cl-Tyr/mol Tyr; medians p = .11) and protein carbonyls (0.347 vs. 0.339 nmol/mg protein; medians p = .56) were not significantly increased in asthmatics. Levels of 3-bromotyrosine were strongly correlated with eosinophil peroxidase protein (r = 0.79, p < .0001). There were no significant correlations between the markers of oxidative stress and lung function. We conclude that eosinophil peroxidase produces substantial amounts of hypobromous acid in the airways of stable asthmatics. Although this highly reactive oxidant is a strong candidate for exacerbating inflammatory tissue damage in the lung, its role in asthma remains uncertain.
The Canterbury Respiratory Research Group, Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand.
Ruth E
RE
Aldridge
Tim
T
Chan
Christine J
CJ
van Dalen
Revathy
R
Senthilmohan
Marti
M
Winn
Per
P
Venge
G Ian
GI
Town
Anthony J
AJ
Kettle
D000328:Adult; D000368:Aged; D001249:Asthma / Q000201:enzymology* / Q000378:metabolism; D001959:Bromates / Q000378:metabolism*; D001966:Bromine / Q000378:metabolism; D002713:Chlorine / Q000378:metabolism; D047209:Eosinophil Peroxidase; D005260:Female; D005609:Free Radicals; D006219:Halogens / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism*; D013183:Sputum / Q000378:metabolism
D001959:Bromates; D005609:Free Radicals; D006219:Halogens; D002713:Chlorine; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D009195:Peroxidase; C027664:hypobromous acid; D010100:Oxygen; D001966:Bromine