Cargando…

Nitric oxide alters hyaluronan deposition by airway smooth muscle cells

Asthma is a chronic inflammatory disease that is known to cause changes in the extracellular matrix, including changes in hyaluronan (HA) deposition. However, little is known about the factors that modulate its deposition or the potential consequences. Asthmatics with high levels of exhaled nitric o...

Descripción completa

Detalles Bibliográficos
Autores principales: Majors, Alana K., Chakravarti, Ritu, Ruple, Lisa M., Leahy, Rachel, Stuehr, Dennis J., Lauer, Mark, Erzurum, Serpil C., Janocha, Allison, Aronica, Mark A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028120/
https://www.ncbi.nlm.nih.gov/pubmed/29966020
http://dx.doi.org/10.1371/journal.pone.0200074
_version_ 1783336716235440128
author Majors, Alana K.
Chakravarti, Ritu
Ruple, Lisa M.
Leahy, Rachel
Stuehr, Dennis J.
Lauer, Mark
Erzurum, Serpil C.
Janocha, Allison
Aronica, Mark A.
author_facet Majors, Alana K.
Chakravarti, Ritu
Ruple, Lisa M.
Leahy, Rachel
Stuehr, Dennis J.
Lauer, Mark
Erzurum, Serpil C.
Janocha, Allison
Aronica, Mark A.
author_sort Majors, Alana K.
collection PubMed
description Asthma is a chronic inflammatory disease that is known to cause changes in the extracellular matrix, including changes in hyaluronan (HA) deposition. However, little is known about the factors that modulate its deposition or the potential consequences. Asthmatics with high levels of exhaled nitric oxide (NO) are characterized by greater airway reactivity and greater evidence of airway inflammation. Based on these data and our previous work we hypothesized that excessive NO promotes the pathologic production of HA by airway smooth muscle cells (SMCs). Exposure of cultured SMCs to various NO donors results in the accumulation of HA in the form of unique, cable-like structures. HA accumulates rapidly after exposure to NO and can be seen as early as one hour after NO treatment. The cable-like HA in NO-treated SMC cultures supports the binding of leukocytes. In addition, NO produced by murine macrophages (RAW cells) and airway epithelial cells also induces SMCs to produce HA cables when grown in co-culture. The modulation of HA by NO appears to be independent of soluble guanylate cyclase. Taken together, NO-induced production of leukocyte-binding HA by SMCs provides a new potential mechanism for the non-resolving airway inflammation in asthma and suggests a key role of non-immune cells in driving the chronic inflammation of the submucosa. Modulation of NO, HA and the consequent immune cell interactions may serve as potential therapeutic targets in asthma.
format Online
Article
Text
id pubmed-6028120
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-60281202018-07-19 Nitric oxide alters hyaluronan deposition by airway smooth muscle cells Majors, Alana K. Chakravarti, Ritu Ruple, Lisa M. Leahy, Rachel Stuehr, Dennis J. Lauer, Mark Erzurum, Serpil C. Janocha, Allison Aronica, Mark A. PLoS One Research Article Asthma is a chronic inflammatory disease that is known to cause changes in the extracellular matrix, including changes in hyaluronan (HA) deposition. However, little is known about the factors that modulate its deposition or the potential consequences. Asthmatics with high levels of exhaled nitric oxide (NO) are characterized by greater airway reactivity and greater evidence of airway inflammation. Based on these data and our previous work we hypothesized that excessive NO promotes the pathologic production of HA by airway smooth muscle cells (SMCs). Exposure of cultured SMCs to various NO donors results in the accumulation of HA in the form of unique, cable-like structures. HA accumulates rapidly after exposure to NO and can be seen as early as one hour after NO treatment. The cable-like HA in NO-treated SMC cultures supports the binding of leukocytes. In addition, NO produced by murine macrophages (RAW cells) and airway epithelial cells also induces SMCs to produce HA cables when grown in co-culture. The modulation of HA by NO appears to be independent of soluble guanylate cyclase. Taken together, NO-induced production of leukocyte-binding HA by SMCs provides a new potential mechanism for the non-resolving airway inflammation in asthma and suggests a key role of non-immune cells in driving the chronic inflammation of the submucosa. Modulation of NO, HA and the consequent immune cell interactions may serve as potential therapeutic targets in asthma. Public Library of Science 2018-07-02 /pmc/articles/PMC6028120/ /pubmed/29966020 http://dx.doi.org/10.1371/journal.pone.0200074 Text en © 2018 Majors 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Majors, Alana K.
Chakravarti, Ritu
Ruple, Lisa M.
Leahy, Rachel
Stuehr, Dennis J.
Lauer, Mark
Erzurum, Serpil C.
Janocha, Allison
Aronica, Mark A.
Nitric oxide alters hyaluronan deposition by airway smooth muscle cells
title Nitric oxide alters hyaluronan deposition by airway smooth muscle cells
title_full Nitric oxide alters hyaluronan deposition by airway smooth muscle cells
title_fullStr Nitric oxide alters hyaluronan deposition by airway smooth muscle cells
title_full_unstemmed Nitric oxide alters hyaluronan deposition by airway smooth muscle cells
title_short Nitric oxide alters hyaluronan deposition by airway smooth muscle cells
title_sort nitric oxide alters hyaluronan deposition by airway smooth muscle cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028120/
https://www.ncbi.nlm.nih.gov/pubmed/29966020
http://dx.doi.org/10.1371/journal.pone.0200074
work_keys_str_mv AT majorsalanak nitricoxidealtershyaluronandepositionbyairwaysmoothmusclecells
AT chakravartiritu nitricoxidealtershyaluronandepositionbyairwaysmoothmusclecells
AT ruplelisam nitricoxidealtershyaluronandepositionbyairwaysmoothmusclecells
AT leahyrachel nitricoxidealtershyaluronandepositionbyairwaysmoothmusclecells
AT stuehrdennisj nitricoxidealtershyaluronandepositionbyairwaysmoothmusclecells
AT lauermark nitricoxidealtershyaluronandepositionbyairwaysmoothmusclecells
AT erzurumserpilc nitricoxidealtershyaluronandepositionbyairwaysmoothmusclecells
AT janochaallison nitricoxidealtershyaluronandepositionbyairwaysmoothmusclecells
AT aronicamarka nitricoxidealtershyaluronandepositionbyairwaysmoothmusclecells