Document Detail


Myeloperoxidase-dependent oxidative metabolism of nitric oxide in the cystic fibrosis airway.
MedLine Citation:
PMID:  20080069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-01-15
Journal Detail:
Title:  Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society     Volume:  9     ISSN:  1873-5010     ISO Abbreviation:  J. Cyst. Fibros.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-23     Completed Date:  2010-06-17     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  101128966     Medline TA:  J Cyst Fibros     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  84-92     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Affiliation:
Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of California, Davis, California 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Biological Availability
Breath Tests
Cystic Fibrosis / metabolism*
Exhalation
Female
Humans
Hydrogen Peroxide / metabolism
Male
Nitrates / metabolism
Nitric Oxide / metabolism*
Nitrites / metabolism
Oxidation-Reduction
Peroxidase / metabolism*
Respiratory Mucosa / metabolism
Respiratory System / metabolism*
Sputum / metabolism
Young Adult
Grant Support
ID/Acronym/Agency:
#HL07013/HL/NHLBI NIH HHS; #HL92506/HL/NHLBI NIH HHS; R21 HL092506-02/HL/NHLBI NIH HHS; T32 HL007013-33/HL/NHLBI NIH HHS; UL1 RR024146/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Nitrates; 0/Nitrites; 10102-43-9/Nitric Oxide; 7722-84-1/Hydrogen Peroxide; EC 1.11.1.7/Peroxidase
Comments/Corrections

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