title: Apyrase treatment prevents ischemia-reperfusion injury in rat lung isografts.
abstract: OBJECTIVE
  Endothelial cells express the ectoenzyme ectonucleoside adenosine triphosphate diphosphohydrolase, an apyrase that inhibits vascular inflammation by catalyzing the hydrolysis of adenosine triphosphate and adenosine diphosphate. However, ectonucleoside adenosine triphosphate diphosphohydrolase expression is rapidly lost following oxidative stress, leading to the potential for adenosine triphosphate and related purigenic nucleotides to exacerbate acute solid organ inflammation and injury. We asked if administration of a soluble recombinant apyrase APT102 attenuates lung graft injury in a cold ischemia reperfusion model of rat syngeneic orthotopic lung transplantation.
  
  
  METHODS
  Male Fisher 344 donor lungs were cold preserved in a low-potassium dextrose solution in the presence or absence of APT102 for 18 hours prior to transplantation into syngeneic male Fisher 344 recipients. Seven minutes after reperfusion, lung transplant recipients received either a bolus of APT102 or vehicle (saline solution). Four hours after reperfusion, APT102- and saline solution-treated groups were evaluated for lung graft function and inflammation.
  
  
  RESULTS
  APT102 significantly reduced lung graft extracellular pools of adenosine triphosphate and adenosine diphosphate, improved oxygenation, and protected against pulmonary edema. Apyrase treatment was associated with attenuated neutrophil graft sequestration and less evidence of tissue inflammation as assessed by myeloperoxidase activity, expression of proinflammatory mediators, and numbers of apoptotic endothelial cells.
  
  
  CONCLUSIONS
  Administration of a soluble recombinant apyrase promotes lung function and limits the tissue damage induced by prolonged cold storage, indicating that extracellular purigenic nucleotides play a key role in promoting ischemia-reperfusion injury following lung transplantation.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Mo 63110-1013, USA.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Sugimoto
authors.forename: Xue
authors.initials: X
authors.lastname: Lin
authors.forename: Jiaming
authors.initials: J
authors.lastname: Lai
authors.forename: Mikio
authors.initials: M
authors.lastname: Okazaki
authors.forename: Nitin A
authors.initials: NA
authors.lastname: Das
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Krupnick
authors.forename: Ridong
authors.initials: R
authors.lastname: Chen
authors.forename: Soon Seog
authors.initials: SS
authors.lastname: Jeong
authors.forename: G A
authors.initials: GA
authors.lastname: Patterson
authors.forename: Daniel
authors.initials: D
authors.lastname: Kreisel
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Gelman
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001081:Apyrase / Q000494:pharmacology*; D001998:Bronchopulmonary Sequestration; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism; D007958:Leukocyte Count; D016040:Lung Transplantation / Q000009:adverse effects / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000166:cytology; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
chemical_list: D018925:Chemokines; D016207:Cytokines; D011994:Recombinant Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009195:Peroxidase; D001081:Apyrase