TY - JOUR
T1 - Recipient intramuscular gene transfer of active transforming growth factor-β1 attenuates acute lung rejection
AU - Suda, Takashi
AU - D'Ovidio, Franco
AU - Daddi, Niccolo
AU - Ritter, Jon H.
AU - Mohanakumar, Thalachallour
AU - Patterson, G. Alexander
N1 - Funding Information:
We thank Dr Debra A. Hullett (Department of Surgery, University of Wisconsin, Madison, WI) for kindly providing adenovirus encoding TGF-β1. We also thank Kathleen Grapperhaus for technical assistance, Dawn Schuessler and Mary Ann Kelly for secretarial support, and Diane Toeniskoetter for her assistance. Statistical advice was obtained from Richard B. Schuessler, PhD. This work was supported by National Institutes of Health (NIH) grant 1 R01 HL-41281; T.M. is supported by NIH grant HL-56643.
PY - 2001/5
Y1 - 2001/5
N2 - 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.
AB - 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.
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U2 - 10.1016/S0003-4975(01)02528-0
DO - 10.1016/S0003-4975(01)02528-0
M3 - Article
C2 - 11383816
AN - SCOPUS:0034996056
SN - 0003-4975
VL - 71
SP - 1651
EP - 1656
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 5
ER -