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Right arrow Lung - transplantation

Ann Thorac Surg 2001;71:1651-1656
© 2001 The Society of Thoracic Surgeons

Original article: general thoracic

Recipient intramuscular gene transfer of active transforming growth factor-ß1 attenuates acute lung rejection

Takashi Suda, MDa, Franco D’Ovidio, MDa, Niccolo Daddi, MDa, Jon H. Ritter, MDb, Thalachallour Mohanakumar, PhDa,c, G. Alexander Patterson, MD, FRCS(C)a

a Division of Cardiothoracic Surgery, Washington University School of Medicine, Barnes Jewish Hospital, St. Louis, Missouri, USA
b Department of Pathology, Washington University School of Medicine, Barnes Jewish Hospital, St. Louis, Missouri, USA
c Department of Immunology, Washington University School of Medicine, Barnes Jewish Hospital, St. Louis, Missouri, USA

Address reprint requests to Dr Patterson, Division of Cardiothoracic Surgery, Washington University School of Medicine, One Barnes Jewish Hospital Plaza, 3108 Queeny Tower, St. Louis, MO 63110
e-mail: pattersona{at}msnotes.wustl.edu

Presented at the Thirty-seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 29–31, 2001.

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 ß1 (group I, n = 6), ß-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 ß1 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 ß1 showed granulation tissue with fibroblast accumulation.

Conclusions. Intramuscular adenovirus-mediated gene transfer of active transforming growth factor ß1 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.




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