Abstract
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.
Highlights
Asthma is a multifactorial, chronic inflammatory disease of the airway whose etiology is poorly understood and that affects more than 24 million Americans
NOC-18 has a half-life of approximately 20h under the culture conditions and mediates a slow release of nitric oxide (NO) during the culture period[64]. 500 μM NaNO2 or 500 μM NaNO3 were used as controls
Hyaluronan in smooth muscle cell (SMC) cultures treated with 500 μM NaNO2 or 500 μM NaNO3 is comparable to that in untreated controls
Summary
Chronic inflammatory disease of the airway whose etiology is poorly understood and that affects more than 24 million Americans (see the Center for Disease Control report for 2015 that can be found at https://www.cdc.gov/asthma/most_recent_data.htm). Only agents that cause endoplasmic reticulum stress, double stranded RNA, and dextran sulfate promote the deposition of HA into cable-like structures by cultured SMCs[29,30,31] These cable-like structures of HA, but not other forms of HA produced by SMCs, bind immune cells[29,30,31]. The cGMP that is formed activates protein kinase G, which, through modulation of calcium levels, causes smooth muscle relaxation[49]. This results in vasodilation, and bronchial dilation[51,52]. The potential role of sGC in modulating HA deposition was examined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
