The effect of organ-specific @entity8238 / XXXX enzymatic activity inhibitor-preconditioning on acute pulmonary allograft rejection.

@entity63 @entity8238 @entity1975 @entity205 @entity12180 @entity35 @entity72395
BACKGROUND: Systemic inhibition of serum @entity8238 ( @entity8238 ) enzymatic activity abrogated acute rejection of pulmonary allografts, whereas organ-specific inhibition ameliorated @entity63 /reperfusion injury in syngeneic transplants. Here, we analyze the effect of allograft-specific inhibitor preconditioning on acute rejection in the presence of @entity205 -based immunosuppressive therapy. METHODS: Orthotopic left single lung transplantation (Tx) in @entity35 (LBNF1 to LEWIS). Control (n=5) grafts were flushed with Perfadex alone, whereas treated (n=5) transplants were perfused with Perfadex and @entity72395 , a specific inhibitor of @entity8238 / @entity8238 enzymatic activity. All recipients were treated with 2.5 mg of @entity205 /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 ( @entity12180 ) and @entity1975 ( @entity1975 ) at explantation ( @entity12180 ) and at day 5 ( @entity12180 , @entity1975 ) was performed with determination of protein levels for @entity1975 and mRNA for @entity12180 . RESULTS: Grafts from treated versus controls showed significantly increased oxygenation capacity (P<.008), correlating with significantly less acute rejection (P<.02). @entity1975 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 @entity12180 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 @entity12180 in treated animals. CONCLUSION: Perfusion with a specific inhibitor of @entity8238 / @entity8238 enzymatic activity was associated with sustained preservation of pulmonary @entity12180 levels, correlating with an amelioration of the acute rejection cascade.
