Abnormal pro-gly-pro pathway and airway neutrophilia in pediatric cystic fibrosis.
Airway Remodeling
/ immunology
Bronchoalveolar Lavage Fluid
/ immunology
Bronchoscopy
/ methods
Chemotaxis, Leukocyte
/ immunology
Child
Cystic Fibrosis
/ diagnosis
Female
Humans
Infant, Newborn
Inflammation
/ metabolism
Leukocyte Elastase
/ metabolism
Male
Matrix Metalloproteinase 9
/ metabolism
Neutrophils
/ immunology
Oligopeptides
/ metabolism
Proline
/ analogs & derivatives
Prolyl Oligopeptidases
/ metabolism
Sputum
/ immunology
Cystic fibrosis
Matrikine
Neutrophil
Protease
Journal
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
18
02
2019
revised:
07
05
2019
accepted:
21
05
2019
pubmed:
10
6
2019
medline:
23
6
2021
entrez:
10
6
2019
Statut:
ppublish
Résumé
Proline-glycine-proline (PGP) is a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP-9) and prolylendopeptidase (PE), and capable of eliciting neutrophil chemotaxis and epithelial remodelling. PGP is normally then degraded by leukotriene A Broncho-alveolar lavage (BAL) fluid was obtained from 38 CF (9 newborns and 29 older children) and 24 non-CF children. BAL cell differentials and levels of PGP, MMP-9, PE and LTA Whilst PGP was present in all but one of the older CF children tested, it was absent in non-CF controls and the vast majority of CF newborns. BAL levels of MMP-9 and PE were elevated in older children with CF relative to CF newborns and non-CF controls, correlating with airway neutrophilia and supportive of PGP generation. Furthermore, despite extracellular LTA A striking imbalance between PGP-generating and -degrading enzymes enables PGP accumulation in CF children from early life and potentially supports airway neutrophilia.
Sections du résumé
BACKGROUND
Proline-glycine-proline (PGP) is a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP-9) and prolylendopeptidase (PE), and capable of eliciting neutrophil chemotaxis and epithelial remodelling. PGP is normally then degraded by leukotriene A
METHODS
Broncho-alveolar lavage (BAL) fluid was obtained from 38 CF (9 newborns and 29 older children) and 24 non-CF children. BAL cell differentials and levels of PGP, MMP-9, PE and LTA
RESULTS
Whilst PGP was present in all but one of the older CF children tested, it was absent in non-CF controls and the vast majority of CF newborns. BAL levels of MMP-9 and PE were elevated in older children with CF relative to CF newborns and non-CF controls, correlating with airway neutrophilia and supportive of PGP generation. Furthermore, despite extracellular LTA
CONCLUSIONS
A striking imbalance between PGP-generating and -degrading enzymes enables PGP accumulation in CF children from early life and potentially supports airway neutrophilia.
Identifiants
pubmed: 31176670
pii: S1569-1993(19)30769-6
doi: 10.1016/j.jcf.2019.05.017
pmc: PMC7001103
pii:
doi:
Substances chimiques
Oligopeptides
0
prolyl-glycyl-proline
0
Proline
9DLQ4CIU6V
Prolyl Oligopeptidases
EC 3.4.21.26
Leukocyte Elastase
EC 3.4.21.37
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
40-48Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL110950
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL114439
Pays : United States
Organisme : Wellcome Trust
ID : 209458/Z/17/Z
Pays : United Kingdom
Organisme : BLRD VA
ID : I01 BX001756
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL102371
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL126596
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL077783
Pays : United States
Organisme : Wellcome Trust
ID : 086718/Z/08/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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