Low-dose endobronchial gene transfer to ameliorate lung graft ischemia-reperfusion injury

Tsutomu Tagawa, Takashi Suda, Niccolò Daddi, Benjamin D. Kozower, Samer A. Kanaan, T. Mohanakumar, G. Alexander Patterson

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Objective: This study was undertaken to determine whether low-dose endobronchial transfer to the donor of the gene for human interleukin 10 would decrease ischemiareperfusion injury in lung transplantation. Methods: Experiments used male Fischer rats. Donor animals underwent right thoracotomy. A catheter was introduced into the left main bronchus, and vector was instilled. Group I (n = 6) received 2 × 107 plaque-forming units of adenovirus encoding human interleukin 10, group II (n = 6) received an adenovirus control encoding β-galactosidase, and group III (n = 6) received saline solution. After instillation the left main bronchus was clamped for 60 minutes. Lungs were removed 24 hours later and stored in low-potassium dextran glucose solution for 18 hours before left lung transplantation. Graft function was assessed at 24 hours immediately before the animals were killed. Ratio of wet to dry weight and tissue myeloperoxidase activity were measured. Transgenic expression of human interleukin 10 was evaluated by means of enzyme-linked immunosorbent assay and immunohistochemical assay. Results: Arterial oxygenation was significantly improved in group I relative to groups II and III (257.6 ± 59.7 mm Hg vs 114.6 ± 66.9 mm Hg and 118.6 ± 91.1 mm Hg, P = .008 and P = .007, respectively). Neutrophil sequestration, as measured by myeloperoxidase activity, was also significantly reduced in group I relative to groups II and III (0.141 ± 0.025 vs 0.304 ± 0.130 and 0.367 ± 0.153 Δ optical density units/[min · mg protein], P = .029 and P = .004, respectively). Enzyme-linked immunosorbent assay and immunohistochemical assay demonstrated the expression of human interleukin 10 in transfected lungs only. Conclusions: Low-dose endobronchial transfer to the donor of the gene for human interleukin 10 ameliorated ischemia-reperfusion injury in rodent lung transplantation by improving graft oxygenation and reducing neutrophil sequestration. Only 2 × 107 plaque-forming units of adenoviral vector were required for functional transgenic expression. Endobronchial gene transfer to lung grafts may be a useful delivery route even at low doses.

Original languageEnglish
Pages (from-to)795-802
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume123
Issue number4
DOIs
Publication statusPublished - 2002

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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