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

Anders Jeppsson, Carlo Pellegrini, Timothy O'Brien, Virginia M. Miller, Henry D. Tazelaar, C. Burcin Taner, Christopher G.A. McGregor

Research output: Contribution to journalArticle

5 Scopus citations

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 transgene product and increased NO production. Increasing NO from eNOS does not affect histogically identified acute rejection.

Original languageEnglish (US)
Pages (from-to)S591-S596
JournalTransplant International
Volume13
Issue numberSUPPL. 1
DOIs
StatePublished - 2000

Keywords

  • Acute rejection
  • Gene transfer
  • Lung transplantation
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Transplantation

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