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The Role of Ectonucleotidases CD39 and CD73 and Adenosine Signaling in Solid Organ Transplantation.

Roberts V, Stagg J, Dwyer KM - Front Immunol (2014)

Bottom Line: Extracellular adenosine is a potent immunomodulatory molecule that accumulates in states of inflammation.Nucleotides such as adenosine triphosphate and adenosine diphosphate are release from injured and necrotic cells and hydrolyzed to adenosine monophosphate and adenosine by the concerted action of the ectonucleotidases CD39 and CD73.Furthermore, the purinergic pathway is intrinsically involved in B and T cell biology and function.

View Article: PubMed Central - PubMed

Affiliation: Immunology Research Centre, St. Vincent's Hospital Melbourne and Department of Medicine, The University of Melbourne , Melbourne, VIC , Australia.

ABSTRACT
Extracellular adenosine is a potent immunomodulatory molecule that accumulates in states of inflammation. Nucleotides such as adenosine triphosphate and adenosine diphosphate are release from injured and necrotic cells and hydrolyzed to adenosine monophosphate and adenosine by the concerted action of the ectonucleotidases CD39 and CD73. Accumulating evidence suggest that purinergic signaling is involved in the inflammatory response that accompanies acute rejection and chronic allograft dysfunction. Modification of the purinergic pathway has been shown to alter graft survival in a number of solid organ transplant models and the response to ischemia-reperfusion injury (IRI). Furthermore, the purinergic pathway is intrinsically involved in B and T cell biology and function. Although T cells have traditionally been considered the orchestrators of acute allograft rejection, a role for B cells in chronic allograft loss is being increasingly appreciated. This review focuses on the role of the ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation including the effects on IRI and T and B cell biology.

No MeSH data available.


Related in: MedlinePlus

Protective mechanisms in solid organ transplantation. Extracellular adenosine is generated from the enzymatic hydrolysis of nucleotides by the ectoenzymes CD39 and CD73 expressed on endothelial cells (EC) and B cells. Adenosine signals via A2AR on circulating cells including regulatory T cells (Treg) and via A2BR expressed both on the vasculature and inflammatory cells. Experimental strategies which improve graft outcome for each solid organ transplant are listed in boxes.
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Figure 1: Protective mechanisms in solid organ transplantation. Extracellular adenosine is generated from the enzymatic hydrolysis of nucleotides by the ectoenzymes CD39 and CD73 expressed on endothelial cells (EC) and B cells. Adenosine signals via A2AR on circulating cells including regulatory T cells (Treg) and via A2BR expressed both on the vasculature and inflammatory cells. Experimental strategies which improve graft outcome for each solid organ transplant are listed in boxes.

Mentions: The ectonucleotidases CD39 and CD73 are involved in adenosine generation and expressed by these important immune cell subsets. Adenosine signaling is integral to the function of both B and T cells, is protective in warm and cold ischemic injury and has immunomodulating properties, see Figure 1. There are current adenosine receptor agonists and antagonists being tested [reviewed in Ref. (74)] in non-transplant human trials but the ubiquitous nature of adenosine receptors make targeted therapy difficult. Potentially treatment of the donor organ prior to implantation with adenosine receptor agonists may reduce the impact of ischemia–reperfusion injury, subsequent acute rejection and graft failure.


The Role of Ectonucleotidases CD39 and CD73 and Adenosine Signaling in Solid Organ Transplantation.

Roberts V, Stagg J, Dwyer KM - Front Immunol (2014)

Protective mechanisms in solid organ transplantation. Extracellular adenosine is generated from the enzymatic hydrolysis of nucleotides by the ectoenzymes CD39 and CD73 expressed on endothelial cells (EC) and B cells. Adenosine signals via A2AR on circulating cells including regulatory T cells (Treg) and via A2BR expressed both on the vasculature and inflammatory cells. Experimental strategies which improve graft outcome for each solid organ transplant are listed in boxes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927137&req=5

Figure 1: Protective mechanisms in solid organ transplantation. Extracellular adenosine is generated from the enzymatic hydrolysis of nucleotides by the ectoenzymes CD39 and CD73 expressed on endothelial cells (EC) and B cells. Adenosine signals via A2AR on circulating cells including regulatory T cells (Treg) and via A2BR expressed both on the vasculature and inflammatory cells. Experimental strategies which improve graft outcome for each solid organ transplant are listed in boxes.
Mentions: The ectonucleotidases CD39 and CD73 are involved in adenosine generation and expressed by these important immune cell subsets. Adenosine signaling is integral to the function of both B and T cells, is protective in warm and cold ischemic injury and has immunomodulating properties, see Figure 1. There are current adenosine receptor agonists and antagonists being tested [reviewed in Ref. (74)] in non-transplant human trials but the ubiquitous nature of adenosine receptors make targeted therapy difficult. Potentially treatment of the donor organ prior to implantation with adenosine receptor agonists may reduce the impact of ischemia–reperfusion injury, subsequent acute rejection and graft failure.

Bottom Line: Extracellular adenosine is a potent immunomodulatory molecule that accumulates in states of inflammation.Nucleotides such as adenosine triphosphate and adenosine diphosphate are release from injured and necrotic cells and hydrolyzed to adenosine monophosphate and adenosine by the concerted action of the ectonucleotidases CD39 and CD73.Furthermore, the purinergic pathway is intrinsically involved in B and T cell biology and function.

View Article: PubMed Central - PubMed

Affiliation: Immunology Research Centre, St. Vincent's Hospital Melbourne and Department of Medicine, The University of Melbourne , Melbourne, VIC , Australia.

ABSTRACT
Extracellular adenosine is a potent immunomodulatory molecule that accumulates in states of inflammation. Nucleotides such as adenosine triphosphate and adenosine diphosphate are release from injured and necrotic cells and hydrolyzed to adenosine monophosphate and adenosine by the concerted action of the ectonucleotidases CD39 and CD73. Accumulating evidence suggest that purinergic signaling is involved in the inflammatory response that accompanies acute rejection and chronic allograft dysfunction. Modification of the purinergic pathway has been shown to alter graft survival in a number of solid organ transplant models and the response to ischemia-reperfusion injury (IRI). Furthermore, the purinergic pathway is intrinsically involved in B and T cell biology and function. Although T cells have traditionally been considered the orchestrators of acute allograft rejection, a role for B cells in chronic allograft loss is being increasingly appreciated. This review focuses on the role of the ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation including the effects on IRI and T and B cell biology.

No MeSH data available.


Related in: MedlinePlus