Recipient intramuscular gene transfer of active transforming growth factor-β1 attenuates acute lung rejection

Takashi Suda, Franco D'Ovidio, Niccolo Daddi, Jon H. Ritter, Thalachallour Mohanakumar, G. Alexander Patterson

研究成果: Article査読

23 被引用数 (Scopus)

抄録

Background. Gene transfer into the donor graft has been demonstrated to be feasible in reducing ischemia-reperfusion injury and rejection in lung transplantation. This study was undertaken to determine whether intramuscular gene transfer into the recipient can also reduce subsequent lung graft rejection. Methods. Brown Norway rats served as donors and F344 rats as recipients. Recipient animals were injected with 1010 plaque-forming units of adenovirus encoding active transforming growth factor β1 (group I, n = 6), β-galactosidase as adenoviral controls (group II, n = 6), or normal saline without adenovirus (group III, n = 6) into both gluteus muscles 2 days before transplantation. Gene expression was confirmed by enzyme-linked immunosorbent assay. Graft function was assessed on postoperative day 5. Results. Successful gene transfection and expression were confirmed by the presence of active transforming growth factor β1 protein in muscle and plasma. Oxygenation was significantly improved in group I (group I vs II and III, 353.6 ± 63.0 mm Hg vs 165.7 ± 39.9 and 119.1 ± 41.5 mm Hg; p = 0.02 and 0.004). The muscle transfected with the transforming growth factor β1 showed granulation tissue with fibroblast accumulation. Conclusions. Intramuscular adenovirus-mediated gene transfer of active transforming growth factor β1 into the recipients attenuates acute lung rejection as manifested by significantly improved oxygenation in transplanted lung allografts. This intramuscular transfection approach as a cytokine therapy is feasible in transplantation and may be useful in reducing rejection as well as reperfusion injury.

本文言語English
ページ(範囲)1651-1656
ページ数6
ジャーナルAnnals of Thoracic Surgery
71
5
DOI
出版ステータスPublished - 05-2001
外部発表はい

All Science Journal Classification (ASJC) codes

  • 外科
  • 呼吸器内科
  • 循環器および心血管医学

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