Activation of A3 adenosine receptor provides lung protection against ischemia-reperfusion injury associated with reduction in apoptosis.
Apoptosis has been described in various models of ischemia-reperfusion (IR) injury, including lung transplantation. A3 adenosine receptor (AR) has been linked to a variety of apoptotic processes. The effect of A3AR activation on lung injury and apoptosis, following IR, has not been reported to date. In a spontaneously breathing cat model, in which the left lower lobe of the lung was isolated and subjected to 2 h of ischemia and 3 h of reperfusion, we tested the effect of IB-MECA, a selective A3AR agonist, on lung apoptosis and injury. Significant increase in the extent of apoptosis was observed following lung reperfusion. IB-MECA, administered before IR, and before or with reperfusion, markedly (p < 0.01) attenuated indices of injury and apoptosis including the percentage of injured alveoli, wet/dry weight ratio, myeloperoxidase activity, in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) positive cells, and caspase 3 activity and expression. The protective effects of IB-MECA were completely blocked by pretreatment with the selective A3AR antagonist MRS-1191. In summary, even when given after the onset of ischemia, the A3AR agonist IB-MECA conferred a powerful protection against reperfusion lung injury, which was associated with decreased apoptosis. This suggests a potentially important role for A3AR in lung IR injury.
Rivo
Julia
J
Department of Anesthesiology & Critical Care Medicine, Hadassah University Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
Zeira
Evelyne
E
Galun
Eithan
E
Matot
Idit
I
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002415:Cats; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D055370:Lung Injury; D043684:Receptor, Adenosine A3 / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D043684:Receptor, Adenosine A3; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D000241:Adenosine