title: Myeloperoxidase-dependent oxidative metabolism of nitric oxide in the cystic fibrosis airway.
abstract: BACKGROUND
  Decreased expired nitric oxide (eNO) is commonly observed in cystic fibrosis (CF) patients and is usually explained by dysregulation of NO synthase (NOS) isoforms in respiratory tract epithelium. Later stages of this disease are accompanied by intense airway infiltration of phagocytes with high NOS activity, abundant levels of the hemoprotein myeloperoxidase (MPO) and significant production of significant reactive oxygen species.
  
  
  METHODS
  This study characterizes the contribution of the high airway levels of MPO to decreased eNO levels in adult CF patients. NO metabolites (NO(x)) and MPO levels in fresh sputum of control and adult CF patients were determined and related to measurements of eNO and to in vitro consumption of NO in CF sputum.
  
  
  RESULTS
  Despite essentially equal levels of NO(x) in sputum, eNO was 2- to 3-fold lower in CF patients compared to healthy controls. In CF patients, eNO levels were negatively associated with sputum peroxidase activity. In vivo correlations were confirmed by ex vivo studies of NO consumption by MPO in CF sputum. Immunodepletion studies confirmed MPO as the major heme peroxidase in CF sputum contributing to the hydrogen peroxide (H(2)O(2))-dependent consumption of NO.
  
  
  CONCLUSIONS
  In CF airways MPO acts as a phagocyte-derived NO oxidase that diminishes NO bioavailability at airway surfaces, possibly identifying this peroxidase as a potential target for therapeutic intervention.
authors.affiliation: Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, California 95616, USA.
authors.forename: Anna L P
authors.initials: AL
authors.lastname: Chapman
authors.forename: Brian M
authors.initials: BM
authors.lastname: Morrissey
authors.forename: Vihas T
authors.initials: VT
authors.lastname: Vasu
authors.forename: Maya M
authors.initials: MM
authors.lastname: Juarez
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Houghton
authors.forename: Chin-Shang
authors.initials: CS
authors.lastname: Li
authors.forename: Carroll E
authors.initials: CE
authors.lastname: Cross
authors.forename: Jason P
authors.initials: JP
authors.lastname: Eiserich
mesh_terms: D000328:Adult; D001682:Biological Availability; D001944:Breath Tests; D003550:Cystic Fibrosis / Q000378:metabolism*; D045853:Exhalation; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism*; D013183:Sputum / Q000378:metabolism; D055815:Young Adult
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D009195:Peroxidase