Abstract:
BACKGROUND:Systemic inhibition of serum CD26/dipeptidylpeptidase (DPP IV) enzymatic activity abrogated acute rejection of pulmonary allografts, whereas organ-specific inhibition ameliorated ischemia/reperfusion injury in syngeneic transplants. Here, we analyze the effect of allograft-specific inhibitor preconditioning on acute rejection in the presence of cyclosporine-based immunosuppressive therapy. METHODS:Orthotopic left single lung transplantation (Tx) in rats (LBNF1 to LEWIS). Control (n=5) grafts were flushed with Perfadex alone, whereas treated (n=5) transplants were perfused with Perfadex and AB192, a specific inhibitor of CD26/DPP IV enzymatic activity. All recipients were treated with 2.5 mg of cyclosporine A/kg per day subcutaneously after Tx. Recipients were sacrificed at day 5 after Tx, and oxygenation capacity was measured. In addition, staining for vasoactive intestinal peptide (VIP) and proliferating cell nuclear antigen (PCNA) at explantation (VIP) and at day 5 (VIP, PCNA) was performed with determination of protein levels for PCNA and mRNA for VIP. RESULTS:Grafts from treated versus controls showed significantly increased oxygenation capacity (P<.008), correlating with significantly less acute rejection (P<.02). PCNA staining and protein expression were significantly lower in perivascular and bronchial epithelial cells (P=.001) in treated versus controls. There was significantly higher staining for VIP at the time of Tx in alveolar macrophages in treated versus controls (P=.001), which was seen up to day 5 post-Tx in both macrophages and respiratory epithelium (P=.001) with elevated mRNA expression for VIP in treated animals. CONCLUSION:Perfusion with a specific inhibitor of CD26/DPP IV enzymatic activity was associated with sustained preservation of pulmonary VIP levels, correlating with an amelioration of the acute rejection cascade.
journal_name
Transplantationjournal_title
Transplantationauthors
Jungraithmayr W,Oberreiter B,De Meester I,Wiedl T,Inci I,Bain M,Augustyns K,Hillinger S,Scharpé S,Weder W,Korom Sdoi
10.1097/TP.0b013e3181b08e77subject
Has Abstractpub_date
2009-08-27 00:00:00pages
478-85issue
4eissn
0041-1337issn
1534-6080pii
00007890-200908270-00007journal_volume
88pub_type
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