title: Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia.
abstract: Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia.
  
  
  
  Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague-Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A2Badenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A(A2AAR) and A2Badenosine receptor (A2BAR) mRNA and protein were quantified.
  
  
  
  Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2AAR mRNA and protein concentrations remained unchanged following ischemia. A2BAR protein was increased in PA ligated lungs of SS rats after 7 days, and 4 h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes.
  
  
  
  Increased A2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A2BAR mutant rats implicate a protective role for A2BAR signaling in countering ischemic lung injury.
authors.affiliation: a Children's Research Institute , Milwaukee , Wisconsin , USA.|b Clinical and Translational Science Institute , Milwaukee , Wisconsin , USA.|c Medical College of Wisconsin , Milwaukee , Wisconsin , USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Densmore
authors.affiliation: c Medical College of Wisconsin , Milwaukee , Wisconsin , USA.
authors.forename: Terry R
authors.initials: TR
authors.lastname: Schaid
authors.affiliation: a Children's Research Institute , Milwaukee , Wisconsin , USA.|c Medical College of Wisconsin , Milwaukee , Wisconsin , USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Jeziorczak
authors.affiliation: c Medical College of Wisconsin , Milwaukee , Wisconsin , USA.
authors.forename: Meetha
authors.initials: M
authors.lastname: Medhora
authors.affiliation: d Marquette University , Milwaukee , Wisconsin , USA.
authors.forename: Said
authors.initials: S
authors.lastname: Audi
authors.affiliation: c Medical College of Wisconsin , Milwaukee , Wisconsin , USA.
authors.forename: Shraddha
authors.initials: S
authors.lastname: Nayak
authors.affiliation: c Medical College of Wisconsin , Milwaukee , Wisconsin , USA.
authors.forename: John
authors.initials: J
authors.lastname: Auchampach
authors.affiliation: c Medical College of Wisconsin , Milwaukee , Wisconsin , USA.
authors.forename: Melinda R
authors.initials: MR
authors.lastname: Dwinell
authors.affiliation: c Medical College of Wisconsin , Milwaukee , Wisconsin , USA.
authors.forename: Aron M
authors.initials: AM
authors.lastname: Geurts
authors.affiliation: b Clinical and Translational Science Institute , Milwaukee , Wisconsin , USA.|c Medical College of Wisconsin , Milwaukee , Wisconsin , USA.|e Clement J. Zablocki Veterans Affairs Medical Center , Milwaukee , Wisconsin , USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Jacobs
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D018549:Cryptogenic Organizing Pneumonia / Q000517:prevention & control*; D007511:Ischemia; D055370:Lung Injury / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000032:analysis / Q000235:genetics; D043704:Receptor, Adenosine A2B / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D000241:Adenosine
keywords: A2B adenosine receptor; bronchiolitis obliterans organizing pneumonia; lung ischemia; lung transplant