Additive protection against lung ischemia-reperfusion injury by adenosine A2A receptor activation before procurement and during reperfusion

Gazoni, Leo M.; Laubach, Victor E.; Mulloy, Daniel P.; Bellizzi, Andrew M.; Unger, Eric B.; Linden, Joel; Ellman, Peter I.; Lisle, Turner C.; Krön, Irving L.

doi:10.1016/j.jtcvs.2007.08.041

Cited by 52 publications

(62 citation statements)

References 30 publications

(37 reference statements)

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“…Ischemia-reperfusion lung injury was attenuated by ATP-MgCl 2 in rats, although its effect was in part mediated by its breakdown product, adenosine, via A 2 receptors, probably on leukocytes, acting to prevent the production of damaging O 2 -derived free radicals (Hsu et al, 1994;Hirata et al, 2001;Chen et al, 2003). A 2A receptor agonists attenuated cardiac dysfunction arising from pulmonary ischemia-reperfusion injury (Reece et al, 2005;Ellman et al, 2008;Gazoni et al, 2008;Sharma et al, 2009). It has been claimed that A 2B receptors play a role in mediating lung inflammation after ischemia-reperfusion by stimulating cytokine production and neutrophil chemotaxis (Anvari et al, 2010).…”

Section: Ischemiamentioning

confidence: 99%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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Section: Ischemiamentioning

confidence: 99%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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“…We have previously demonstrated that A 2A R agonism significantly attenuates lung IR injury (23,33,34) and have defined a pivotal role of iNKT cell-produced IL-17 in the initiation of lung injury and inflammation after IR (3). A 2A R is the predominant adenosine receptor on iNKT cells (35).…”

Section: Original Articlementioning

confidence: 99%

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A_2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury

Sharma

LaPar

Stone

et al. 2016

Am J Respir Crit Care Med

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Rationale: Ischemia-reperfusion (IR) injury after lung transplantation, which affects both short-and long-term allograft survival, involves activation of NADPH oxidase 2 (NOX2) and activation of invariant natural killer T (iNKT) cells to produce IL-17. Adenosine A 2A receptor (A 2A R) agonists are known to potently attenuate lung IR injury and IL-17 production. However, mechanisms for iNKT cell activation after IR and A 2A R agonist-mediated protection remain unclear.Objectives: We tested the hypothesis that NOX2 mediates IL-17 production by iNKT cells after IR and that A 2A R agonism prevents IR injury by blocking NOX2 activation in iNKT cells.Methods: An in vivo murine hilar ligation model of IR injury was used, in which left lungs underwent 1 hour of ischemia and 2 hours of reperfusion.Measurements and Main Results: Adoptive transfer of iNKT cells from p47 phox2/2 or NOX2 2/2 mice to Ja18 2/2 (iNKT cell-deficient) mice significantly attenuated lung IR injury and IL-17 production. Treatment with an A 2A R agonist attenuated IR injury and IL-17 production in wild-type (WT) mice and in Ja18 2/2 mice reconstituted with WT, but not A 2A R 2/2, iNKT cells. Furthermore, the A 2A R agonist prevented IL-17 production by murine and human iNKT cells after acute hypoxia-reoxygenation by blocking p47 phox phosphorylation, a critical step for NOX2 activation.Conclusions: NOX2 plays a key role in inducing iNKT cell-mediated IL-17 production and subsequent lung injury after IR. A primary mechanism for A 2A R agonist-mediated protection entails inhibition of NOX2 in iNKT cells. Therefore, agonism of A 2A Rs on iNKT cells may be a novel therapeutic strategy to prevent primary graft dysfunction after lung transplantation.

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“…All subtype classes of this receptor (A 1 , A 2A , A 2B and A 3 ) are expressed in lung tissue and work through adenyl cyclase or phospholipase C activation. Some studies attribute an anti-inflammatory role to A 1 , A 2A and A 3 (81) with reduction in oxidative stress by decreasing neutrophil-mediated O 2…”

Section: Adenosine A2a Receptor Agonistsmentioning

confidence: 99%

Oxidative and nitrosative stress during pulmonary ischemia-reperfusion injury: from the lab to the OR

Gielis¹,

Beckers²,

Briedé³

et al. 2017

Ann. Transl. Med.

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Oxidative and nitrosative stress are an umbrella term for pathophysiological processes that involve free radical generation during inflammation. In this review, the involvement of reactive oxygen and nitrogen species is evaluated during lung ischemia-reperfusion injury (LIRI) from a surgical point of view. The main biochemical and cellular mechanisms behind free radical generation are discussed, together with surgical procedures that may cause reperfusion injury. Finally, different therapeutic strategies are further explored. A literature search was performed, searching for "lung ischemia reperfusion injury", "reperfusion injury", "large animal model" and different search terms for each section: "surgery", "treatment", "cellular mechanism", or "enzyme". Although reperfusion injury is not an uncommon entity and there is a lot of evidence concerning myocardial ischemia-reperfusion injury, in the lung this phenomenon is less extensively described and studies in large animals are not easy to come by. With increasing number of patients on waiting lists for lung transplant, awareness for this entity should all but rise.

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Additive protection against lung ischemia-reperfusion injury by adenosine A2A receptor activation before procurement and during reperfusion

Cited by 52 publications

References 30 publications

Purinergic Signaling and Blood Vessels in Health and Disease

Purinergic Signaling and Blood Vessels in Health and Disease

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A_2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury

Oxidative and nitrosative stress during pulmonary ischemia-reperfusion injury: from the lab to the OR

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Additive protection against lung ischemia-reperfusion injury by adenosine A2A receptor activation before procurement and during reperfusion

Cited by 52 publications

References 30 publications

Purinergic Signaling and Blood Vessels in Health and Disease

Purinergic Signaling and Blood Vessels in Health and Disease

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury

Oxidative and nitrosative stress during pulmonary ischemia-reperfusion injury: from the lab to the OR

Contact Info

Product

Resources

About

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A_2A Receptor to Inhibit Lung Ischemia–Reperfusion Injury