A3 adenosine receptor signaling contributes to airway inflammation and mucus production in adenosine deaminase-deficient mice

HWJ Young, JG Molina, D Dimina, H Zhong… - The Journal of …, 2004 - journals.aai.org
HWJ Young, JG Molina, D Dimina, H Zhong, M Jacobson, LNL Chan, TS Chan, JJ Lee…
The Journal of Immunology, 2004journals.aai.org
Adenosine signaling has been implicated in chronic lung diseases such as asthma and
chronic obstructive pulmonary disease; however, the specific roles of the various adenosine
receptors in processes central to these disorders are not well understood. In this study, we
have investigated the role (s) of the A 3 adenosine receptor in adenosine-dependent
pulmonary inflammation observed in adenosine deaminase (ADA)-deficient mice. The A 3
receptor (A 3 R) was found to be expressed in eosinophils and mucus-producing cells in the …
Abstract
Adenosine signaling has been implicated in chronic lung diseases such as asthma and chronic obstructive pulmonary disease; however, the specific roles of the various adenosine receptors in processes central to these disorders are not well understood. In this study, we have investigated the role (s) of the A 3 adenosine receptor in adenosine-dependent pulmonary inflammation observed in adenosine deaminase (ADA)-deficient mice. The A 3 receptor (A 3 R) was found to be expressed in eosinophils and mucus-producing cells in the airways of ADA-deficient mice. Treatment of ADA-deficient mice with MRS 1523, a selective A 3 R antagonist, prevented airway eosinophilia and mucus production. Similar findings were seen in the lungs of ADA/A 3 double knockout mice. Although eosinophils were decreased in the airways of ADA-deficient mice following antagonism or removal of the A 3 R, elevations in circulating and lung interstitial eosinophils persisted, suggesting signaling through the A 3 R is needed for the migration of eosinophils into the airways. These findings identify an important role for the A 3 R in regulating lung eosinophilia and mucus production in an environment of elevated adenosine.
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