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: 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
• Journal: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society (J Cyst Fibros) Vol. 9 Issue 2 Pg. 84-92 (Mar 2010) ISSN: 1873-5010 [Electronic] Netherlands
• PMID: 20080069 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Chemical References

• Nitrates
• Nitrites
• Nitric Oxide
• Hydrogen Peroxide
• Peroxidase

Topics

• Adult
• Biological Availability
• Breath Tests
• Cystic Fibrosis (metabolism)
• Exhalation
• Female
• Humans
• Hydrogen Peroxide (metabolism)
• In Vitro Techniques
• Male
• Nitrates (metabolism)
• Nitric Oxide (metabolism)
• Nitrites (metabolism)
• Oxidation-Reduction
• Peroxidase (metabolism)
• Respiratory Mucosa (metabolism)
• Respiratory System (metabolism)
• Sputum (metabolism)
• Young Adult