Original ContributionIdentifying peroxidases and their oxidants in the early pathology of cystic fibrosis
Section snippets
Materials
Potassium thiocyanate was supplied by Ajax Chemicals (Sydney, Australia) and 3,3′,5,5′-tetramethylbenzidine (TMB) was from Fluka Chemie GmbH (Buchs, Switzerland). p-Nitrophenyl phosphate was supplied by Strem Chemicals (Newburyport, MA, USA). Riboflavin was obtained from Eastman Organic Chemicals (Rochester, NY, USA) and crystal violet was from Peking Chemical Works (Peking, China). L-Tyrosine-U-13C9 and L-tyrosine-ring-13C6 were obtained from Cambridge Isotope Laboratories (Andover, MA, USA).
Characteristics of the study population
Subject characteristics are shown in Table 1. Children in the NCF group were on average 1.5 years older than those in the CF group; the majority (88%) had respiratory symptoms at the time of BAL and almost half had pulmonary infection. Children with CF had an increased number of neutrophils compared to the NCF group, even after adding age as a confounding variable (p = 0.013). Eosinophils were detected in the BALF of 29 children with CF (group geometric mean (95% CI): 5.30 (3.01, 9.33) × 103/ml) and
Discussion
In an earlier study we demonstrated that myeloperoxidase was the predominant peroxidase in BAL from infants with CF and that it produced HOCl [7]. We have now confirmed these findings in a different population of children with CF and extended our work to show that MPO also actively produces HOBr within the airways, and that levels of MPO as well as biomarkers of HOCl and HOBr were increased in the presence of infection and respiratory symptoms. They also correlated with the Kanga score, a
Acknowledgments
We thank the Health Research Council of New Zealand and the Australian Cystic Fibrosis Research Trust for supporting this work. Eline Thomson was supported by the Christchurch School of Medicine and Health Sciences on a McGee Scholarship. Dr. Kettle has received speaking honoraria from AstraZeneca and Lilly and has received research grant support from AstraZeneca. The full authorship of this article includes the members of AREST CF: Elizabeth Balding, Luke J. Berry, Dr. Siobhain Brennan,
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