Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder characterized by a chronic neutrophilic airways inflammation, increasing levels of oxidative stress and reduced levels of antioxidants such as glutathione (GSH). Gamma-glutamyltransferase (GGT), an enzyme induced by oxidative stress...

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Main Authors: Alessandro Corti, Maria Franzini, Silvana Cianchetti, Gabriella Bergamini, Evelina Lorenzini, Paola Melotti, Aldo Paolicchi, Pierluigi Paggiaro, Alfonso Pompella
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3319600?pdf=render
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author Alessandro Corti
Maria Franzini
Silvana Cianchetti
Gabriella Bergamini
Evelina Lorenzini
Paola Melotti
Aldo Paolicchi
Pierluigi Paggiaro
Alfonso Pompella
author_facet Alessandro Corti
Maria Franzini
Silvana Cianchetti
Gabriella Bergamini
Evelina Lorenzini
Paola Melotti
Aldo Paolicchi
Pierluigi Paggiaro
Alfonso Pompella
author_sort Alessandro Corti
collection DOAJ
description BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder characterized by a chronic neutrophilic airways inflammation, increasing levels of oxidative stress and reduced levels of antioxidants such as glutathione (GSH). Gamma-glutamyltransferase (GGT), an enzyme induced by oxidative stress and involved in the catabolism of GSH and its derivatives, is increased in the airways of CF patients with inflammation, but the possible implications of its increase have not yet been investigated in detail. PRINCIPAL FINDINGS: The present study was aimed to evaluate the origin and the biochemical characteristics of the GGT detectable in CF sputum. We found GGT activity both in neutrophils and in the fluid, the latter significantly correlating with myeloperoxidase expression. In neutrophils, GGT was associated with intracellular granules. In the fluid, gel-filtration chromatography showed the presence of two distinct GGT fractions, the first corresponding to the human plasma b-GGT fraction, the other to the free enzyme. The same fractions were also observed in the supernatant of ionomycin and fMLP-activated neutrophils. Western blot analysis confirmed the presence of a single band of GGT immunoreactive peptide in the CF sputum samples and in isolated neutrophils. CONCLUSIONS: In conclusion, our data indicate that neutrophils are able to transport and release GGT, thus increasing GGT activity in CF sputum. The prompt release of GGT may have consequences on all GGT substrates, including major inflammatory mediators such as S-nitrosoglutathione and leukotrienes, and could participate in early modulation of inflammatory response.
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spelling doaj.art-203e8eba47a5441eab33c77c8fcc21512022-12-21T22:37:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3477210.1371/journal.pone.0034772Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum.Alessandro CortiMaria FranziniSilvana CianchettiGabriella BergaminiEvelina LorenziniPaola MelottiAldo PaolicchiPierluigi PaggiaroAlfonso PompellaBACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder characterized by a chronic neutrophilic airways inflammation, increasing levels of oxidative stress and reduced levels of antioxidants such as glutathione (GSH). Gamma-glutamyltransferase (GGT), an enzyme induced by oxidative stress and involved in the catabolism of GSH and its derivatives, is increased in the airways of CF patients with inflammation, but the possible implications of its increase have not yet been investigated in detail. PRINCIPAL FINDINGS: The present study was aimed to evaluate the origin and the biochemical characteristics of the GGT detectable in CF sputum. We found GGT activity both in neutrophils and in the fluid, the latter significantly correlating with myeloperoxidase expression. In neutrophils, GGT was associated with intracellular granules. In the fluid, gel-filtration chromatography showed the presence of two distinct GGT fractions, the first corresponding to the human plasma b-GGT fraction, the other to the free enzyme. The same fractions were also observed in the supernatant of ionomycin and fMLP-activated neutrophils. Western blot analysis confirmed the presence of a single band of GGT immunoreactive peptide in the CF sputum samples and in isolated neutrophils. CONCLUSIONS: In conclusion, our data indicate that neutrophils are able to transport and release GGT, thus increasing GGT activity in CF sputum. The prompt release of GGT may have consequences on all GGT substrates, including major inflammatory mediators such as S-nitrosoglutathione and leukotrienes, and could participate in early modulation of inflammatory response.http://europepmc.org/articles/PMC3319600?pdf=render
spellingShingle Alessandro Corti
Maria Franzini
Silvana Cianchetti
Gabriella Bergamini
Evelina Lorenzini
Paola Melotti
Aldo Paolicchi
Pierluigi Paggiaro
Alfonso Pompella
Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum.
PLoS ONE
title Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum.
title_full Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum.
title_fullStr Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum.
title_full_unstemmed Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum.
title_short Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum.
title_sort contribution by polymorphonucleate granulocytes to elevated gamma glutamyltransferase in cystic fibrosis sputum
url http://europepmc.org/articles/PMC3319600?pdf=render
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