Ischemia/reperfusion injury: The role of CD26/dipeptidyl-peptidase-IV-inhibition in lung transplantation.
CD26/Dipeptidyl peptidase (DPP) IV is an integral membrane protein of lymphocytes that modulates the activities of chemokines, interleukins, and neuropeptides. We investigated the effect of enzymatic DPP IV inhibition on ischemia/reperfusion injury after extended ischemia prior to transplantation.


METHODS
We used a syngeneic rat (Lewis) orthotopic left lung transplantation model. In the control group (group I), donor lungs were flushed and preserved in Perfadex for 18 hours at 4 degrees C, then transplanted and reperfused for 2 hours. Group II donor lungs were perfused with and stored in Perfadex +25mol/L AB192 (bis(4-acetamidophenyl) 1-(S)-prolylpyrrolidine-2(R,S)-phosphonate), a small molecular weight DPP IV inhibitor. After 2-hour reperfusion, we measured blood gas, peak airway pressure, and thiobarbituric acid reactive substances.


RESULTS
Grafts from group II versus group I showed a significantly increased oxygenation capacity (II: 298.4 +/- 87.6 mm Hg vs 120.9 +/- 48.0, P < .01), lower peak airway pressure (11.8 +/- 0.9 mm Hg vs 16.0 +/- 1.4, P < .01), and less lipid peroxidation (9.3 +/- 2.0 micromol/L vs 13.8 +/- 1.8, P < .01).


CONCLUSIONS
Inhibition of intragraft DPP IV enzymatic activity significantly reduced ischemia/reperfusion-associated pulmonary injury, allowing for successful transplantation after 18 hours of ischemia.
Zhai
W
W
Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
Cardell
M
M
De Meester
I
I
Augustyns
K
K
Hillinger
S
S
Inci
I
I
Arni
S
S
Jungraithmayr
W
W
Scharpé
S
S
Weder
W
W
Korom
S
S
D000818:Animals; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D016040:Lung Transplantation / Q000473:pathology / Q000502:physiology*; D063065:Organophosphonates / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D014185:Transplantation, Isogeneic
D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D063065:Organophosphonates; C118220:bis(4-acetamidophenyl) 1-prolylpyrrolidine-2-phosphonate; D011392:Proline