Adenosine A2A receptor activation reduces inflammation and preserves pulmonary function in an in vivo model of lung transplantation

Reece, T. Brett; Ellman, Peter I.; Maxey, Thomas S.; Crosby, Ivan K.; Warren, Patrick; Chong, Tae W.; LeGallo, Robin D.; Linden, Joel; Kern, John A.; Tribble, Curtis G.; Krön, Irving L.

doi:10.1016/j.jtcvs.2004.11.042

Cited by 70 publications

(70 citation statements)

References 28 publications

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“…Previous research on anti-inflammatory properties of A2a mainly focused on ischemia reperfusion-induced tissue injury (22,24,42). In renal reperfusion injury, A2a activation significantly reduced PMN recruitment and maintained organ function (42).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Reutershan

Cagnina

Chang

et al. 2007

The Journal of Immunology

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117

120

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To determine the role of the adenosine receptor A2a in a murine model of LPS-induced lung injury, migration of polymorphonuclear leukocytes (PMNs) into the different compartments of the lung was determined by flow cytometry, microvascular permeability was assessed by the extravasation of Evans blue, and the release of chemotactic cytokines into the alveolar airspace was determined by ELISA. Measurements were performed in wild-type and A2a gene-deficient mice (A2a−/−). To differentiate the role of A2a on hemopoietic and nonhemopoietic cells, we created chimeric mice by transfer of bone marrow (BM) between wild-type and A2a−/− mice and used mice that lacked A2a expression selectively on myeloid cells (A2aflox/flox × LysM-cre). A specific A2a receptor agonist (ATL202) was used to evaluate its potential to reduce lung injury in vivo. In wild-type mice, therapeutic treatment with ATL202 reduced LPS-induced PMN recruitment, and release of cytokines. Pretreatment, but not posttreatment, also reduced Evans blue extravasation. In the BM chimeric mice lacking A2a on BM-derived cells, PMN migration into the alveolar space was increased by ∼50%. These findings were confirmed in A2aflox/flox × LysM-cre mice. ATL202 was only effective when A2a was present on BM-derived cells. A2a agonists may be effective at curbing inflammatory lung tissue damage.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Reutershan

Cagnina

Chang

et al. 2007

The Journal of Immunology

Self Cite

117

120

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“…Swine is the most commonly used large animal model of lung transplantation; often in studies of drug effects on ischemia/reperfusion injury [3,[7][8][9][10], EVLP [1,3] and in xenotransplantation [11,12]. An adequate understanding of pig lung anatomy is important for those beginning experimental protocols.…”

Section: Discussionmentioning

confidence: 99%

“…An adequate understanding of pig lung anatomy is important for those beginning experimental protocols. In our review of the literature, we could not find an article dedicated to the technique of swine lung transplantation; nevertheless, several articles briefly describe their donor and recipient preparation [1,[7][8][9][10]12]. In our described model, a single stage cross-clamp is applied to the left pulmonary hilum and obviates the need for sequential clamping.…”

Section: Discussionmentioning

confidence: 99%

“…We also differ in the order of performing the anastomoses as venous is performed first, followed by bronchial and arterial. Others have suggested ligation of the left pulmonary veins, followed by clamping of the left bronchus and pulmonary artery and cutting them distally for left pneumonectomy; with subsequent performance of the bronchial and arterial anastomoses in sequence and then clamping the recipient's left atrium that is sewed to the donor's left atrial cuff [8,10].…”

Section: Discussionmentioning

confidence: 99%

“…Oxygenation capacity (PaO 2 /FiO 2 ) with arterial blood gases, pulmonary artery pressures and vascular resistance, and dynamic and static lung compliance are used to monitor the transplanted lung performance during reperfusion [1,[7][8][9][10][11][12]. There are three approaches to monitor the transplanted lung.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Technical Pearls for Swine Lung Transplantation

Karimi

Cobb

Staples

et al. 2011

Journal of Surgical Research

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Extracellular cAMP: The Past and Visiting the Future in cAMP‐Enriched Extracellular Vesicles

et al. 2021

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It is recently discovered that the cyclic nucleotide, cyclic adenosine monophosphate (cAMP) can be enriched in the extracellular vesicles (EVs) isolated from endothelial cells. In the current perspective a historical context for the discovery of the extracellular cAMP is provided. The story of extracellular cAMP through investigations addressing the molecule's role in the adenosine pathway is followed, which is widespread in mammalian physiology. The adenosine pathway mediates normal physiological conditions such as renin release, phosphate transport, etc., and participates in pathological conditions such as bronchoconstriction of the airways. Furthermore, adenosine mediated biological pathways are regulated via the receptor mediated intracellular cAMP pathway in mammalian cells. It then speculates on the question of whether cAMP enriched EVs could bypass typical receptor mediated cell signaling and directly activate cAMP signaling cascade in target cells. Preliminary studies to suggest cAMP enriched EVs are provided, added to naïve endothelial cells, results in an increase in intracellular cAMP. An alternate mechanism is proposed, apart from the traditional adenosine pathway, that extracellular cAMP may exert its effects and put into perspective how it might consider circulating cAMP moving forward.

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Adenosine A2A receptor activation reduces inflammation and preserves pulmonary function in an in vivo model of lung transplantation

Abstract: Adenosine A 2A activation during early reperfusion attenuated lung inflammation and preserved pulmonary function in this model of lung transplantation. ATL-146e and similar compounds could play a significant role in improving outcomes of pulmonary transplantation.

Cited by 70 publications

References 28 publications

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Technical Pearls for Swine Lung Transplantation

Extracellular cAMP: The Past and Visiting the Future in cAMP‐Enriched Extracellular Vesicles

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