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

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

Original languageEnglish
JournalTransplant International
Volume13
Issue numberSUPPL. 1
Publication statusPublished - 2000

Fingerprint

Nitric Oxide Synthase Type III
Allografts
Lung
Genes
Nitric Oxide
Galactosidases
Calcium
Alveolar Epithelial Cells
Lung Transplantation
Transgenes
Immunosuppression
Histology
Proteins
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Transplantation

Cite this

Jeppsson, A., Pellegrini, C., O'Brien, T., Miller, V. M., Tazelaar, H. D., Taner, C. B., & McGregor, C. G. A. (2000). Gene transfer of endothelial nitric oxide synthase to pulmonary allografts: Impact on acute rejection. Transplant International, 13(SUPPL. 1).

Gene transfer of endothelial nitric oxide synthase to pulmonary allografts : Impact on acute rejection. / Jeppsson, Anders; Pellegrini, Carlo; O'Brien, Timothy; Miller, Virginia M.; Tazelaar, Henry D.; Taner, C. Burcin; McGregor, Christopher G A.

In: Transplant International, Vol. 13, No. SUPPL. 1, 2000.

Research output: Contribution to journalArticle

Jeppsson, A, Pellegrini, C, O'Brien, T, Miller, VM, Tazelaar, HD, Taner, CB & McGregor, CGA 2000, 'Gene transfer of endothelial nitric oxide synthase to pulmonary allografts: Impact on acute rejection', Transplant International, vol. 13, no. SUPPL. 1.
Jeppsson, Anders ; Pellegrini, Carlo ; O'Brien, Timothy ; Miller, Virginia M. ; Tazelaar, Henry D. ; Taner, C. Burcin ; McGregor, Christopher G A. / Gene transfer of endothelial nitric oxide synthase to pulmonary allografts : Impact on acute rejection. In: Transplant International. 2000 ; Vol. 13, No. SUPPL. 1.
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