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

Autor: Densmore JC; 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., Schaid TR; c Medical College of Wisconsin , Milwaukee , Wisconsin , USA., Jeziorczak PM; a Children's Research Institute , Milwaukee , Wisconsin , USA.; c Medical College of Wisconsin , Milwaukee , Wisconsin , USA., Medhora M; c Medical College of Wisconsin , Milwaukee , Wisconsin , USA., Audi S; d Marquette University , Milwaukee , Wisconsin , USA., Nayak S; c Medical College of Wisconsin , Milwaukee , Wisconsin , USA., Auchampach J; c Medical College of Wisconsin , Milwaukee , Wisconsin , USA., Dwinell MR; c Medical College of Wisconsin , Milwaukee , Wisconsin , USA., Geurts AM; c Medical College of Wisconsin , Milwaukee , Wisconsin , USA., Jacobs ER; 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.
Jazyk: angličtina
Zdroj: Experimental lung research [Exp Lung Res] 2017 Feb; Vol. 43 (1), pp. 38-48. Date of Electronic Publication: 2017 Mar 07.
DOI: 10.1080/01902148.2017.1286697
Abstrakt: 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.
Databáze: MEDLINE
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