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Novel Pathway of Adenosine Generation in the Lungs from NAD(+): Relevance to Allergic Airway Disease

Adenosine and uric acid (UA) play a pivotal role in lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). In the present experiments, we measured adenosine synthesis from nicotinamide adenine dinucleotide (NAD(+)) in membranes prepared from wild type (WT) and CD38 knockout (...

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Autores principales: Graeff, Richard, Guedes, Alonso, Quintana, Ruth, Wendt-Hornickle, Erin, Baldo, Caroline, Walseth, Timothy, O’Grady, Scott, Kannan, Mathur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663290/
https://www.ncbi.nlm.nih.gov/pubmed/33120985
http://dx.doi.org/10.3390/molecules25214966
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author Graeff, Richard
Guedes, Alonso
Quintana, Ruth
Wendt-Hornickle, Erin
Baldo, Caroline
Walseth, Timothy
O’Grady, Scott
Kannan, Mathur
author_facet Graeff, Richard
Guedes, Alonso
Quintana, Ruth
Wendt-Hornickle, Erin
Baldo, Caroline
Walseth, Timothy
O’Grady, Scott
Kannan, Mathur
author_sort Graeff, Richard
collection PubMed
description Adenosine and uric acid (UA) play a pivotal role in lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). In the present experiments, we measured adenosine synthesis from nicotinamide adenine dinucleotide (NAD(+)) in membranes prepared from wild type (WT) and CD38 knockout (CD38KO) mouse lungs, from cultured airway smooth muscle and epithelial cells, and in bronchoalveolar lavage fluid after airway challenge with epidemiologically relevant allergens. Adenosine was determined using an enzymatically coupled assay that produces ATP and is detected by luminescence. Uric acid was determined by ELISA. Exposure of cultured airway epithelial cells to Alternaria alternata extract caused significant nucleotide (NAD(+) and ATP) release in the culture media. The addition of NAD(+) to membranes prepared from WT mice resulted in faster generation of adenosine compared to membranes from CD38KO mice. Formation of adenosine from NAD(+) affected UA and ATP concentrations, its main downstream molecules. Furthermore, NAD(+) and adenosine concentrations in the bronchoalveolar lavage fluid decreased significantly following airway challenge with house-dust mite extract in WT but not in CD38KO mice. Thus, NAD(+) is a significant source of adenosine and UA in the airways in mouse models of allergic airway disease, and the capacity for their generation from NAD(+) is augmented by CD38, a major NADase with high affinity for NAD(+). This novel non-canonical NAD(+)-adenosine-UA pathway that is triggered by allergens has not been previously described in the airways.
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spelling pubmed-76632902020-11-14 Novel Pathway of Adenosine Generation in the Lungs from NAD(+): Relevance to Allergic Airway Disease Graeff, Richard Guedes, Alonso Quintana, Ruth Wendt-Hornickle, Erin Baldo, Caroline Walseth, Timothy O’Grady, Scott Kannan, Mathur Molecules Article Adenosine and uric acid (UA) play a pivotal role in lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). In the present experiments, we measured adenosine synthesis from nicotinamide adenine dinucleotide (NAD(+)) in membranes prepared from wild type (WT) and CD38 knockout (CD38KO) mouse lungs, from cultured airway smooth muscle and epithelial cells, and in bronchoalveolar lavage fluid after airway challenge with epidemiologically relevant allergens. Adenosine was determined using an enzymatically coupled assay that produces ATP and is detected by luminescence. Uric acid was determined by ELISA. Exposure of cultured airway epithelial cells to Alternaria alternata extract caused significant nucleotide (NAD(+) and ATP) release in the culture media. The addition of NAD(+) to membranes prepared from WT mice resulted in faster generation of adenosine compared to membranes from CD38KO mice. Formation of adenosine from NAD(+) affected UA and ATP concentrations, its main downstream molecules. Furthermore, NAD(+) and adenosine concentrations in the bronchoalveolar lavage fluid decreased significantly following airway challenge with house-dust mite extract in WT but not in CD38KO mice. Thus, NAD(+) is a significant source of adenosine and UA in the airways in mouse models of allergic airway disease, and the capacity for their generation from NAD(+) is augmented by CD38, a major NADase with high affinity for NAD(+). This novel non-canonical NAD(+)-adenosine-UA pathway that is triggered by allergens has not been previously described in the airways. MDPI 2020-10-27 /pmc/articles/PMC7663290/ /pubmed/33120985 http://dx.doi.org/10.3390/molecules25214966 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Graeff, Richard
Guedes, Alonso
Quintana, Ruth
Wendt-Hornickle, Erin
Baldo, Caroline
Walseth, Timothy
O’Grady, Scott
Kannan, Mathur
Novel Pathway of Adenosine Generation in the Lungs from NAD(+): Relevance to Allergic Airway Disease
title Novel Pathway of Adenosine Generation in the Lungs from NAD(+): Relevance to Allergic Airway Disease
title_full Novel Pathway of Adenosine Generation in the Lungs from NAD(+): Relevance to Allergic Airway Disease
title_fullStr Novel Pathway of Adenosine Generation in the Lungs from NAD(+): Relevance to Allergic Airway Disease
title_full_unstemmed Novel Pathway of Adenosine Generation in the Lungs from NAD(+): Relevance to Allergic Airway Disease
title_short Novel Pathway of Adenosine Generation in the Lungs from NAD(+): Relevance to Allergic Airway Disease
title_sort novel pathway of adenosine generation in the lungs from nad(+): relevance to allergic airway disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663290/
https://www.ncbi.nlm.nih.gov/pubmed/33120985
http://dx.doi.org/10.3390/molecules25214966
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