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Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia. Exp Lung Res 2017 02;43(1):38-48 PMID: 28266889 PMCID: PMC5831175

Pubmed ID

28266889

Abstract

: 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 adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A (AAR) and A adenosine receptor (AAR) 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. AAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. AAR mRNA and protein concentrations remained unchanged following ischemia. AAR 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 AAR and adenosine following unilateral lung ischemia as well as more BOOP in AAR mutant rats implicate a protective role for AAR signaling in countering ischemic lung injury.

Author List

Densmore JC, Schaid TR, Jeziorczak PM, Medhora M, Audi S, Nayak S, Auchampach J, Dwinell MR, Geurts AM, Jacobs ER

Authors

John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
John C. Densmore MD Associate Professor in the Surgery department at Medical College of Wisconsin
Melinda R. Dwinell PhD Center Associate Director, Associate Professor in the Physiology department at Medical College of Wisconsin
Aron Geurts PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Meetha M. Medhora PhD Professor in the Radiation Oncology department at Medical College of Wisconsin




Scopus

2-s2.0-85014510215   3 Citations

MESH terms used to index this publication - Major topics in bold

Adenosine
Animals
Cryptogenic Organizing Pneumonia
Ischemia
Lung Injury
RNA, Messenger
Rats
Receptor, Adenosine A2A
Receptor, Adenosine A2B
Signal Transduction
jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6