Myeloperoxidase-dependent oxidative metabolism of nitric oxide in the cystic fibrosis airway.
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.
Chapman
Anna L P
AL
Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, California 95616, USA.
Morrissey
Brian M
BM
Vasu
Vihas T
VT
Juarez
Maya M
MM
Houghton
Jessica S
JS
Li
Chin-Shang
CS
Cross
Carroll E
CE
Eiserich
Jason P
JP
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
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D009195:Peroxidase