Gene transfer of endothelial nitric oxide synthase to pulmonary allografts: impact on acute rejection

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Abstract
Experiments were designed to study whether overexpression of nitric oxide (NO) from endothelial nitric oxide synthase (eNOS) affects acute rejection. Allogenic, orthotopic single‐lung transplantation was performed after transbronchial adenoviral‐mediated gene transfer (3 × 108 pfu) of either of eNOS or β‐galactosidase to donor lungs of rats (n = 6 each). No immunosuppression was used. After 4 days, transplanted lungs were prepared for enzyme activity, cGMP and histology. Calcium‐dependent NOS activity, reflecting eNOS, was greater in eNOS‐transduced lungs (587 ± 97 vs 2.1 ± 1.4 pmol/mg protein per h, P < 0.001). In contrast, calcium‐independent NOS activity, reflecting iNOS, was comparable. Concentrations of cGMP were higher in eNOS‐transduced lungs (13.2 ± 2.3 vs 4.9 ± 0.5 pmol/mg protein). Positive immunostaining for eNOS was present in pneumocytes only in eNOS‐transduced lungs. No difference in histological grade of rejection was observed. eNOS gene transfer to pulmonary allografts results in a functionally active trans‐gene product and increased NO production. Increasing NO from eNOS does not affect histogically identified acute rejection.