Myeloperoxidase and protein oxidation in cystic fibrosis

Cystic fibrosis (CF) is associated with chronic pulmonary inflammation and progressive lung dysfunction, possibly associated with the formation of neu trophil myeloperoxidase (MPO)-derived oxidants. Expectorated sputum specime ns from adult CF patients were analyzed for MPO characteristic protein modi fications 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 wer e slightly reduced in CF. However, there was a slight increase in protein-a ssociated 3-nitrotyrosine in CF sputum compared with controls, reflecting t he formation of reactive nitrogen intermediates, possibly through MPO-catal yzed oxidation of NO2-. CF sputum MPO was found to contribute to oxidant-me diated cytotoxicity toward cultured tracheobronchial epithelial cells; howe ver, peroxidase-dependent protein oxidation occurred primarily within sputu m proteins, suggesting scavenging of MPO-derived oxidants by CF mucus and p erhaps formation of secondary cytotoxic products within CF sputum. Our find ings demonstrate the formation of MPO-derived oxidizing and possibly nitrat ing species within the respiratory tract of subjects with CF, which collect ively may contribute to bronchial injury and respiratory failure in CF.