Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia

• Published in: Experimental lung research Vol. 43; no. 1; pp. 38 - 48
• Main Authors: Densmore, John C., Schaid, Terry R., Jeziorczak, Paul M., Medhora, Meetha, Audi, Said, Nayak, Shraddha, Auchampach, John, Dwinell, Melinda R., Geurts, Aron M., Jacobs, Elizabeth R.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.02.2017
• Subjects: Adenosine - pharmacology; adenosine receptor; Animals; bronchiolitis obliterans organizing pneumonia; Cryptogenic Organizing Pneumonia - prevention & control; Ischemia; Lung Injury - metabolism; lung ischemia; lung transplant; Rats; Receptor, Adenosine A2A - analysis; Receptor, Adenosine A2A - genetics; Receptor, Adenosine A2B - analysis; Receptor, Adenosine A2B - genetics; Receptor, Adenosine A2B - physiology; RNA, Messenger - analysis; Signal Transduction - physiology; lung ischemia; lung transplant; A2B adenosine receptor; bronchiolitis obliterans organizing pneumonia
• ISSN: 0190-2148; 1521-0499; 1521-0499
• DOI: 10.1080/01902148.2017.1286697

Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. Materials and Methods: 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 A 2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A 2A (A 2A AR) and A 2B adenosine receptor (A 2B AR) mRNA and protein were quantified. Results: Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A 2B AR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A 2A AR mRNA and protein concentrations remained unchanged following ischemia. A 2B AR 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. Conclusion: Increased A 2B AR and adenosine following unilateral lung ischemia as well as more BOOP in A 2B AR mutant rats implicate a protective role for A 2B AR signaling in countering ischemic lung injury.