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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Main Authors:	Grasemann, Hartmut, Shehnaz, Darakhshanda, Enomoto, Masahiro, Leadley, Michael, Belik, Jaques, Ratjen, Felix
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465344/

id	pubmed-3465344
recordtype	oai_dc
spelling	pubmed-34653442012-10-15 L-Ornithine Derived Polyamines in Cystic Fibrosis Airways Grasemann, Hartmut Shehnaz, Darakhshanda Enomoto, Masahiro Leadley, Michael Belik, Jaques Ratjen, Felix Research Article 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. Public Library of Science 2012-10-05 /pmc/articles/PMC3465344/ /pubmed/23071598 http://dx.doi.org/10.1371/journal.pone.0046618 Text en © 2012 Grasemann et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Grasemann, Hartmut Shehnaz, Darakhshanda Enomoto, Masahiro Leadley, Michael Belik, Jaques Ratjen, Felix
spellingShingle	Grasemann, Hartmut Shehnaz, Darakhshanda Enomoto, Masahiro Leadley, Michael Belik, Jaques Ratjen, Felix L-Ornithine Derived Polyamines in Cystic Fibrosis Airways
author_facet	Grasemann, Hartmut Shehnaz, Darakhshanda Enomoto, Masahiro Leadley, Michael Belik, Jaques Ratjen, Felix
author_sort	Grasemann, Hartmut
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
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.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465344/
_version_	1611914154331865088

L-Ornithine Derived Polyamines in Cystic Fibrosis Airways

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