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Title
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The effect of organ-specific CD26/DPP IV enzymatic activity inhibitor-preconditioning on acute pulmonary allograft rejection
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Transplantation. - Baltimore, Md, 1963, currens
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Publication
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Baltimore, Md
:
2009
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ISSN
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0041-1337
1534-6080
[online]
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Volume/pages
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88
:4
(2009)
, p. 478-485
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ISI
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000269303200007
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Full text (Publisher's DOI)
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