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

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

doi:10.1016/j.jcf.2009.10.001

« Previous Next »Journal of Cystic Fibrosis
Volume 9, Issue 2 , Pages 84-92, March 2010

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

Anna L.P. Chapman
- Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, California 95616, USA
- Current address: Free Radical Research Group, Department of Pathology, University of Otago, Christchurch, New Zealand.
Brian M. Morrissey
- Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, California 95616, USA
Vihas T. Vasu
- Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, California 95616, USA
Maya M. Juarez
- Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, California 95616, USA
Jessica S. Houghton
- Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, California 95616, USA
Chin-Shang Li
- Department of Public Health Sciences, Division of Biostatistics, School of Medicine, University of California, Davis, California 95616, USA
Carroll E. Cross
- Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, California 95616, USA
- Department of Physiology and Membrane Biology, University of California, Davis, California 95616, USA
Jason P. Eiserich
- Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, California 95616, USA
- Department of Physiology and Membrane Biology, University of California, Davis, California 95616, USA
- Corresponding author. Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, Davis, California 95616 USA. Tel.: +1 530 752 4008; fax: +1 530 752 8632.

Received 30 January 2008; received in revised form 5 August 2009; accepted 1 October 2009.

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 (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.

Keywords: Myeloperoxidase, Expired nitric oxide, Sputum, Oxidants, Oxidative stress, Neutrophils