Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul 15;22(14):7561.
doi: 10.3390/ijms22147561.

The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis

Tomohiro Kawasumi  1 , Sachio Takeno  1 , Chie Ishikawa  1 , Daisuke Takahara  1 , Takayuki Taruya  1 , Kota Takemoto  1 , Takao Hamamoto  1 , Takashi Ishino  1 , Tsutomu Ueda  1
Affiliations
Review

The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis

Tomohiro Kawasumi et al. Int J Mol Sci. .

Abstract

The human paranasal sinuses are the major source of intrinsic nitric oxide (NO) production in the human airway. NO plays several roles in the maintenance of physiological homeostasis and the regulation of airway inflammation through the expression of three NO synthase (NOS) isoforms. Measuring NO levels can contribute to the diagnosis and assessment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS). In symptomatic AR patients, pro-inflammatory cytokines upregulate the expression of inducible NOS (iNOS) in the inferior turbinate. Excessive amounts of NO cause oxidative damage to cellular components, leading to the deposition of cytotoxic substances. CRS phenotype and endotype classifications have provided insights into modern treatment strategies. Analyses of the production of sinus NO and its metabolites revealed pathobiological diversity that can be exploited for useful biomarkers. Measuring nasal NO based on different NOS activities is a potent tool for specific interventions targeting molecular pathways underlying CRS endotype-specific inflammation. We provide a comprehensive review of the functional diversity of NOS isoforms in the human sinonasal system in relation to these two major nasal disorders' pathologies. The regulatory mechanisms of NOS expression associated with the substrate bioavailability indicate the involvement of both type 1 and type 2 immune responses.

Keywords: allergic rhinitis; arginase; chronic rhinosinusitis; eosinophil; isoform; nasal NO; nitric oxide (NO); nitric oxide synthase; paranasal sinus; redox pathway.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Expression and distribution of different NOS isoforms in human sinonasal mucosa. NOS: nitric oxide synthase; ROS: reactive oxygen species; IHC: immunohistochemistry; DHTM: Ros-dihydrotetramethylrosamine; DAF2-DA: 4,5-diaminofluorescein diacetate.
Figure 2
Figure 2
A delicate balance of the NOS/arginase activities in the human sinonasal system modifies the bioavailability of the NOS substrate based on CRS phenotypes. CRS: chronic rhinosinusitis; ECRS: eosinophilic chronic rhinosinusitis; NO: nitric oxide; NOS: nitric oxide synthase; ONOO−: peroxynitrite; O2: superoxide.
See this image and copyright information in PMC

References

    1. American Thoracic Society. European Respiratory Society ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005. Am. J. Respir. Crit. Care Med. 2005;171:912–930. doi: 10.1164/rccm.200406-710ST. - DOI - PubMed
    1. Dweik R.A., Boggs P.B., Erzurum S.C., Irvin C.G., Leigh M.W., Lundberg J.O., Olin A.-C., Plummer A.L., Taylor D.R. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications. Am. J. Respir. Crit. Care Med. 2011;184:602–615. doi: 10.1164/rccm.9120-11ST. - DOI - PMC - PubMed
    1. Vanhoutte P.M., Zhao Y., Xu A., Leung S.W. Thirty Years of Saying NO: Sources, Fate, Actions, and Misfortunes of the Endothelium-Derived Vasodilator Mediator. Circ. Res. 2016;119:375–396. doi: 10.1161/CIRCRESAHA.116.306531. - DOI - PubMed
    1. Zhu H.-Y., Hong F.-F., Yang S.-L. The Roles of Nitric Oxide Synthase/Nitric Oxide Pathway in the Pathology of Vascular Dementia and Related Therapeutic Approaches. Int. J. Mol. Sci. 2021;22:4540. doi: 10.3390/ijms22094540. - DOI - PMC - PubMed
    1. Maniscalco M., Sofia M., Pelaia G. Nitric Oxide in Upper Airways Inflammatory Diseases. Inflamm. Res. 2007;56:58–69. doi: 10.1007/s00011-006-6111-1. - DOI - PubMed