Article ; Online: Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis.
Matrix biology : journal of the International Society for Matrix Biology
2018 Volume 80, Page(s) 14–28
Abstract: ... of a severe lung influenza virus infection, driven by hyaluronan synthase 2 from epithelial cells ... 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 ...
| Abstract | 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. |
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| MeSH term(s) | 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 ; Influenza, Human/physiopathology ; Macrophages/immunology ; Mice ; Pulmonary Disease, Chronic Obstructive/metabolism ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Pulmonary Disease, Chronic Obstructive/virology ; Respiratory Function Tests | |||||
| Chemical Substances | Alpha-Globulins ; CD44 protein, human ; Cell Adhesion Molecules ; Hyaluronan Receptors ; TNFAIP6 protein, human ; 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) | |||||
| Language | English | |||||
| Publishing date | 2018-06-20 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 1183793-7 | |||||
| ISSN | 1569-1802 ; 0945-053X | |||||
| ISSN (online) | 1569-1802 | |||||
| ISSN | 0945-053X | |||||
| DOI | 10.1016/j.matbio.2018.06.006 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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