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1 Division of Pulmonary/Critical Care Medicine, Department of Internal Medicine, University of California, Davis 95616; 2 Division of Biochemistry and Molecular Biology, University of California, Berkeley, California 94720; and 3 Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama 35233
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 (NO2
) and nitrate
(NO3), 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 NO2. 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.
inflammation; hypochlorous acid; 3-chlorotyrosine; 3,3'-dityrosine; nitric oxide; 3-nitrotyrosine
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