title: A3 adenosine receptor signaling contributes to airway inflammation and mucus production in adenosine deaminase-deficient mice.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
authors.forename: Hays W J
authors.initials: HW
authors.lastname: Young
authors.forename: Jose G
authors.initials: JG
authors.lastname: Molina
authors.forename: Dawn
authors.initials: D
authors.lastname: Dimina
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhong
authors.forename: Marlene
authors.initials: M
authors.lastname: Jacobson
authors.forename: Lee-Nien L
authors.initials: LN
authors.lastname: Chan
authors.forename: Teh-Sheng
authors.initials: TS
authors.lastname: Chan
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Michael R
authors.initials: MR
authors.lastname: Blackburn
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D004804:Eosinophils / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D012333:RNA, Messenger; D043684:Receptor, Adenosine A3; D000243:Adenosine Deaminase