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.
Highlights
Solid organ transplantation is life sustaining and the preferred treatment for patients with end stage organ disease
This review focuses on the role of the ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation including the effects on ischemia–reperfusion injury (IRI) and T and B cell biology
This review focuses on the role of ectonucleotidases (NTPDase1/CD39 and CD73) and adenosine signaling in solid organ transplantation including the effects on IRI and impact on lymphocyte biology
Summary
Solid organ transplantation is life sustaining and the preferred treatment for patients with end stage organ disease. Current immunosuppressive regimens target T cell activation as a means of preventing allograft rejection. The success of this approach is reflected in the exceptional 1 year graft survival of transplanted organs. There is mounting evidence that purinergic signaling is involved in the inflammatory response that accompanies rejection and in chronic allograft dysfunction. This review focuses on the role of ectonucleotidases (NTPDase1/CD39 and CD73) and adenosine signaling in solid organ transplantation including the effects on IRI and impact on lymphocyte biology. CD39, CD73, AND A2BR MEDIATES PROTECTION IN CARDIAC ISCHEMIA–REPERFUSION INJURY CD39 is a ubiquitously expressed integral immune and vascular ectonucleotidase and manipulation of this ectoenzyme is likely to impact on graft rejection in which inflammation and coagulation predominate.
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