title: The impact of purinergic signaling on renal ischemia-reperfusion injury.
abstract: BACKGROUND
  Adenosine provides renovascular protection in mouse models of ischemia-reperfusion injury (I/RI) through purinergic members of the G protein-coupled receptor family, such as the adenosine 2A receptor (A2AR). Ectonucleotidases CD39 and CD73 are integral vascular and immune nucleotidases that regulate extracellular adenosine signaling. Current investigation of CD39 and CD73 in renal I/RI has primarily focused on their respective roles in ischemic preconditioning.
  
  
  METHODS
  In this study, we established a unilateral renal I/RI model and investigated the role of adenosine generation versus nucleotide removal in mediating protection in renal I/RI using mice deficient in CD39, CD73 or A2AR, thereby sequentially disrupting ectonucleotidase cascade and adenosinergic signaling.
  
  
  RESULTS
  Compared with wild-type mice, Cd73 null mice showed reduced levels of serum creatinine and urea, apoptosis of renal cells, and histologic damage after I/RI. Deletion of CD39 was associated with severe renal injury. Administration of apyrase, a soluble form of CD39, decreased global apoptosis and I/RI induced renal injury in wild-type mice. Apyrase treatment also improved renal histology to some extent in A2AR null mice.
  
  
  CONCLUSIONS
  The relative protective effect of CD73 deletion in renal I/RI may reflect an effect of AMP accumulation. Deletion of CD39 showed deleterious effects and administration of soluble CD39 exerted renal protection, which is partially mediated by A2AR. The protective effect conferred by apyrase suggests that supplementing CD39 NTPDase activity may be a useful therapeutic strategy in renal transplantation.
authors.affiliation: Immunology Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia.
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.forename: Siddharth V
authors.initials: SV
authors.lastname: Rajakumar
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
authors.forename: Eddy K F
authors.initials: EK
authors.lastname: Lee
authors.forename: Sandra
authors.initials: S
authors.lastname: Crikis
authors.forename: Anthony J F
authors.initials: AJ
authors.lastname: d'Apice
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cowan
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dwyer
mesh_terms: D015720:5'-Nucleotidase / Q000172:deficiency / Q000502:physiology; D000241:Adenosine / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001081:Apyrase / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D015703:Antigens, CD; D043705:Receptor, Adenosine A2A; D043562:Receptors, G-Protein-Coupled; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine