Adenosine induces airway hyperresponsiveness through activation of A3 receptors on mast cells.
Publication/Presentation Date
7-1-2008
Abstract
BACKGROUND: The mechanisms responsible for the development of airway hyperresponsiveness in asthma are poorly understood. Adenosine levels are high in the lungs of patients with asthma, but a role for adenosine in the development of this cardinal feature of asthma has not been previously reported.
OBJECTIVE: To determine the capacity of adenosine to induce airway hyperresponsiveness, and to investigate the mechanisms behind these effects of adenosine on airway physiology.
METHODS: Wild-type C57BL/6 mice were exposed to aerosolized adenosine analog adenosine-5' N-ethylcarboxamide (NECA), and subsequent hyperresponsiveness to methacholine was investigated by measuring airway mechanics after anesthesia and tracheostomy. Similar experiments were conducted with A(1)-deficient, A(3)-deficient, and mast cell-deficient mice, as well as with mast cell-deficient mice engrafted with wild-type (wt) or A(3)(-/-) mast cells. The effect of NECA on methacholine-induced tension development in ex vivo tracheal rings was also examined.
RESULTS: Exposure of wt mice to NECA resulted in the robust induction of airway hyperresponsiveness. NECA failed to induce hyperresponsiveness to methacholine in tracheal ring preps ex vivo, and NECA-induced airway hyperresponsiveness in vivo was not affected by the genetic inactivation of the A(1) adenosine receptor. In contrast, NECA-induced airway hyperresponsiveness was abolished in A(3) adenosine receptor-deficient mice and in mice deficient in mast cells. Reconstitution of mast cell-deficient mice with wt mast cells restored hyperresponsiveness, whereas reconstitution with A(3) receptor-deficient mast cells did not.
CONCLUSION: Adenosine induces airway hyperresponsiveness indirectly by activating A(3) receptors on mast cells.
Volume
122
Issue
1
First Page
107
Last Page
113
ISSN
1097-6825
Published In/Presented At
Hua, X., Chason, K. D., Fredholm, B. B., Deshpande, D. A., Penn, R. B., & Tilley, S. L. (2008). Adenosine induces airway hyperresponsiveness through activation of A3 receptors on mast cells. The Journal of allergy and clinical immunology, 122(1), 107–113.e1137. https://doi.org/10.1016/j.jaci.2008.03.026
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
18472152
Department(s)
Administration and Leadership
Document Type
Article