Myeloperoxidase-dependent oxidative metabolism of nitric oxide in the cystic fibrosis airway

Anna L P Chapman, Brian M Morrissey, Vihas T. Vasu, Maya M. Juarez, Jessica S. Houghton, Chin-Shang Li, Carroll E Cross, Jason P. Eiserich

Research output: Contribution to journalArticle

14 Scopus citations

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 (NOx) 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 NOx 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 (H2O2)-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.

Original languageEnglish (US)
Pages (from-to)84-92
Number of pages9
JournalJournal of Cystic Fibrosis
Volume9
Issue number2
DOIs
StatePublished - Mar 2010

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Keywords

  • Expired nitric oxide
  • Myeloperoxidase
  • Neutrophils
  • Oxidants
  • Oxidative stress
  • Sputum

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pediatrics, Perinatology, and Child Health

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