title: Intragraft DPP IV inhibition attenuates post-transplant pulmonary ischemia/reperfusion injury after extended ischemia.
abstract: BACKGROUND
  CD26/DPP IV is a T-cell-membrane protein that cleaves dipeptides from extracellular peptides. Inhibition of its enzymatic activity using Pro-Pro-diphenylphosphonate derivatives has been shown to abrogate acute and accelerated rejection in models of cardiac and pulmonary allotransplantation. Here we investigated the effects of enzymatic DPP IV inhibition on ischemia/reperfusion (I/R) injury after extended ischemia before pulmonary transplantation.
  
  
  METHODS
  A syngeneic rat orthotopic left-lung transplantation model was used. Group I donor lungs (controls) were flushed and preserved in Perfadex for 18 hours at 4 degrees C and then transplanted and reperfused for 2 hours. Group II grafts were perfused with and stored in Perfadex + 25 micromol/liter AB192 [bis(4-acetamidophenyl) 1-(S)-prolylpyrrolidine-2(R,S)-phosphonate]. Group III lungs were perfused with Perfadex + AB192, and stored in Perfadex. After 2-hour reperfusion, oxygenation, peak airway pressure (PawP), graft wet/dry (W/D) weight ratio, myeloperoxidase activity, thiobarbituric acid-reactive substances, graft specific DPP IV enzymatic activities and histomorphology were analyzed.
  
  
  RESULTS
  AB192 perfusion significantly reduced DPP IV intragraft enzymatic activity in Groups II and III. Compared with controls, transplants from Groups II and III showed significantly improved oxygenation capacity, PawP and W/D weight ratio, with lower intragraft lipid peroxidation; and preserved histologic structure.
  
  
  CONCLUSIONS
  Targeting intragraft DPP IV enzymatic activity attenuated post-transplantation I/R injury and preserved early graft function after extended ischemia.
authors.affiliation: Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhai
authors.forename: Markus
authors.initials: M
authors.lastname: Cardell
authors.forename: Ingrid
authors.initials: I
authors.lastname: De Meester
authors.forename: Koen
authors.initials: K
authors.lastname: Augustyns
authors.forename: Sven
authors.initials: S
authors.lastname: Hillinger
authors.forename: Ilhan
authors.initials: I
authors.lastname: Inci
authors.forename: Stephan
authors.initials: S
authors.lastname: Arni
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jungraithmayr
authors.forename: Simon
authors.initials: S
authors.lastname: Scharpé
authors.forename: Walter
authors.initials: W
authors.lastname: Weder
authors.forename: Stephan
authors.initials: S
authors.lastname: Korom
mesh_terms: D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D016040:Lung Transplantation; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D058892:Adenosine Deaminase Inhibitors; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins; D007527:Isoenzymes; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4