Faculty Collaboration Database

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

Date

03/08/2017

Pubmed ID

28266889

Pubmed Central ID

PMC5831175

DOI

10.1080/01902148.2017.1286697

Scopus ID

2-s2.0-85014510215 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

UNLABELLED: 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_2AAR) and A_2B adenosine receptor (A_2BAR) 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_2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A_2AAR mRNA and protein concentrations remained unchanged following ischemia. A_2BAR 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_2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A_2BAR mutant rats implicate a protective role for A_2BAR 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
Said Audi PhD Professor in the Biomedical Engineering department at Marquette University
John C. Densmore MD Professor in the Surgery department at Medical College of Wisconsin
Melinda R. Dwinell PhD Professor in the Physiology department at Medical College of Wisconsin
Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin

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