Published ahead of print on June 8, 2006, doi:10.1165/rcmb.2006-0060OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2006-0060OC A3 Adenosine Receptor Signaling Contributes to Airway Mucin Secretion after Allergen ChallengeDepartment of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Medical School; and Department of Pulmonary Medicine, M. D. Anderson Cancer Center, Houston, Texas Correspondence and requests for reprints should be addressed to Michael R. Blackburn, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Medical School, 6431 Fannin, Houston, TX 77030. E-mail: michael.r.blackburn{at}uth.tmc.edu Mucin hypersecretion is a prominent feature of obstructive airway diseases such as asthma. Clara cells conditionally produce mucin in response to inflammatory signals in a process termed mucous metaplasia. This can be followed by mucin secretion stimulated by various signaling molecules. The cellular and molecular mechanisms that regulate mucin production and secretion are not well understood. Adenosine is a signaling nucleoside that has been implicated in airway diseases in which mucus obstruction is prominent. Furthermore, the A3 adenosine receptor (A3AR) is upregulated in mucin-producing goblet cells of the airway, thereby implicating it in processes involved in mucous cell biology. Here we use genetic approaches to investigate the contribution of A3AR signaling to mucus production and secretion in a mouse model of allergen-induced pulmonary disease. We found that the degree of mucin production in response to allergen is similar in wild-type and A3AR-deficient mice, and that overexpression of this receptor in Clara cells neither induces mucin production itself, nor enhances mucin production in response to allergen challenge. Collectively, these experiments demonstrate that the A3AR is neither necessary nor sufficient for mucous cell metaplasia. In contrast to the lack of effect on mucin production, agonist-induced mucin secretion was increased in goblet cells overexpressing the A3AR, and was absent in A3AR-deficient mice. Thus, the A3AR contributes to mucin secretion in allergen-induced metaplasia. Signaling through this receptor may contribute to mucus airway obstruction seen in pulmonary disorders in which adenosine levels are elevated.
Key Words: mucin • mucous cell metaplasia • secretion • adenosine receptors • allergic lung disease This article has been cited by other articles:
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