L-ornithine derived polyamines in cystic fibrosis airways.

Increased arginase activity contributes to airway nitric oxide (NO) deficiency in cystic fibrosis (CF). Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in...

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Autores principales: Hartmut Grasemann, Darakhshanda Shehnaz, Masahiro Enomoto, Michael Leadley, Jaques Belik, Felix Ratjen
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/3b99ae414ef14f90815ebde292b7d81c
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spelling oai:doaj.org-article:3b99ae414ef14f90815ebde292b7d81c2021-11-18T08:13:05ZL-ornithine derived polyamines in cystic fibrosis airways.1932-620310.1371/journal.pone.0046618https://doaj.org/article/3b99ae414ef14f90815ebde292b7d81c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23071598/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Increased arginase activity contributes to airway nitric oxide (NO) deficiency in cystic fibrosis (CF). Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in CF airways and contribute to airway pathophysiology. Polyamine concentrations were measured in sputum of patients with CF and in healthy controls, using liquid chromatography-tandem mass spectrometry. The effect of spermine on airway smooth muscle mechanical properties was assessed in bronchial segments of murine airways, using a wire myograph. Sputum polyamine concentrations in stable CF patients were similar to healthy controls for putrescine and spermidine but significantly higher for spermine. Pulmonary exacerbations were associated with an increase in sputum and spermine levels. Treatment for pulmonary exacerbations resulted in decreases in arginase activity, L-ornithine and spermine concentrations in sputum. The changes in sputum spermine with treatment correlated significantly with changes in L-ornithine but not with sputum inflammatory markers. Incubation of mouse bronchi with spermine resulted in an increase in acetylcholine-induced force and significantly reduced nitric oxide-induced bronchial relaxation. The polyamine spermine is increased in CF airways. Spermine contributes to airways obstruction by reducing the NO-mediated smooth muscle relaxation.Hartmut GrasemannDarakhshanda ShehnazMasahiro EnomotoMichael LeadleyJaques BelikFelix RatjenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e46618 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hartmut Grasemann
Darakhshanda Shehnaz
Masahiro Enomoto
Michael Leadley
Jaques Belik
Felix Ratjen
L-ornithine derived polyamines in cystic fibrosis airways.
description Increased arginase activity contributes to airway nitric oxide (NO) deficiency in cystic fibrosis (CF). Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in CF airways and contribute to airway pathophysiology. Polyamine concentrations were measured in sputum of patients with CF and in healthy controls, using liquid chromatography-tandem mass spectrometry. The effect of spermine on airway smooth muscle mechanical properties was assessed in bronchial segments of murine airways, using a wire myograph. Sputum polyamine concentrations in stable CF patients were similar to healthy controls for putrescine and spermidine but significantly higher for spermine. Pulmonary exacerbations were associated with an increase in sputum and spermine levels. Treatment for pulmonary exacerbations resulted in decreases in arginase activity, L-ornithine and spermine concentrations in sputum. The changes in sputum spermine with treatment correlated significantly with changes in L-ornithine but not with sputum inflammatory markers. Incubation of mouse bronchi with spermine resulted in an increase in acetylcholine-induced force and significantly reduced nitric oxide-induced bronchial relaxation. The polyamine spermine is increased in CF airways. Spermine contributes to airways obstruction by reducing the NO-mediated smooth muscle relaxation.
format article
author Hartmut Grasemann
Darakhshanda Shehnaz
Masahiro Enomoto
Michael Leadley
Jaques Belik
Felix Ratjen
author_facet Hartmut Grasemann
Darakhshanda Shehnaz
Masahiro Enomoto
Michael Leadley
Jaques Belik
Felix Ratjen
author_sort Hartmut Grasemann
title L-ornithine derived polyamines in cystic fibrosis airways.
title_short L-ornithine derived polyamines in cystic fibrosis airways.
title_full L-ornithine derived polyamines in cystic fibrosis airways.
title_fullStr L-ornithine derived polyamines in cystic fibrosis airways.
title_full_unstemmed L-ornithine derived polyamines in cystic fibrosis airways.
title_sort l-ornithine derived polyamines in cystic fibrosis airways.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/3b99ae414ef14f90815ebde292b7d81c
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AT darakhshandashehnaz lornithinederivedpolyaminesincysticfibrosisairways
AT masahiroenomoto lornithinederivedpolyaminesincysticfibrosisairways
AT michaelleadley lornithinederivedpolyaminesincysticfibrosisairways
AT jaquesbelik lornithinederivedpolyaminesincysticfibrosisairways
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