Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis.
Alpha-Globulins
/ metabolism
Animals
Cell Adhesion Molecules
/ metabolism
Endothelial Cells
/ metabolism
Epithelial Cells
/ metabolism
Female
Fibroblasts
/ metabolism
Humans
Hyaluronan Receptors
/ metabolism
Hyaluronan Synthases
/ metabolism
Hyaluronic Acid
/ metabolism
Influenza A Virus, H1N1 Subtype
/ pathogenicity
Influenza, Human
/ metabolism
Macrophages
/ immunology
Mice
Pulmonary Disease, Chronic Obstructive
/ metabolism
Respiratory Function Tests
Fibroblasts
Inflammation
Influenza
Lung
Lung function
Matrix
Journal
Matrix biology : journal of the International Society for Matrix Biology
ISSN: 1569-1802
Titre abrégé: Matrix Biol
Pays: Netherlands
ID NLM: 9432592
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
27
03
2018
revised:
15
06
2018
accepted:
15
06
2018
pubmed:
23
6
2018
medline:
4
12
2019
entrez:
23
6
2018
Statut:
ppublish
Résumé
Little is known about the impact of viral infections on lung matrix despite its important contribution to mechanical stability and structural support. The composition of matrix also indirectly controls inflammation by influencing cell adhesion, migration, survival, proliferation and differentiation. Hyaluronan is a significant component of the lung extracellular matrix and production and degradation must be carefully balanced. We have discovered an imbalance in hyaluronan production following resolution of a severe lung influenza virus infection, driven by hyaluronan synthase 2 from epithelial cells, endothelial cells and fibroblasts. Furthermore hyaluronan is complexed with inter-α-inhibitor heavy chains due to elevated TNF-stimulated gene 6 expression and sequesters CD44-expressing macrophages. We show that intranasal administration of exogenous hyaluronidase is sufficient to release inter-α-inhibitor heavy chains, reduce lung hyaluronan content and restore lung function. Hyaluronidase is already used to facilitate dispersion of co-injected materials in the clinic. It is therefore feasible that fibrotic changes following severe lung infection and inflammation could be overcome by targeting abnormal matrix production.
Identifiants
pubmed: 29933044
pii: S0945-053X(18)30145-8
doi: 10.1016/j.matbio.2018.06.006
pmc: PMC6548309
pii:
doi:
Substances chimiques
Alpha-Globulins
0
CD44 protein, human
0
Cell Adhesion Molecules
0
Hyaluronan Receptors
0
TNFAIP6 protein, human
0
inter-alpha-inhibitor
39346-44-6
Hyaluronic Acid
9004-61-9
HAS2 protein, human
EC 2.4.1.212
Hyaluronan Synthases
EC 2.4.1.212
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14-28Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202865/Z/16/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2018 The Aurthors. Published by Elsevier B.V. All rights reserved.
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