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Eur J Cardiothorac Surg 2005;27:23-27
© 2005 Elsevier Science NL

Attenuation of lung injury in allograft rejection using NF-B decoy transfection—novel strategy for use in lung transplantation

Department of Surgery (E1), Osaka University Graduate School of Medicine, Yamada-oka 2-2, Suita City, Osaka 565-0871, Japan

Received 20 June 2004; received in revised form 31 August 2004; accepted 3 September 2004.

^* Corresponding author. Present Address: Department of General Thoracic Surgery, Kure Medical Center, Aoyamacho 1-3 Kure Hiroshima 737-0023, Japan. Tel.: +81 823 22 3111; fax: +81 823 21 0428. (E-mail: omorik{at}kure-nh.go.jp).

Objective: Increased production of nitric oxide (NO) is known to be a marker of lung allograft rejection and lung injury. NO production is up-regulated directly or indirectly by nuclear factor-kappa B (NF-B), a transcriptional factor of inflammatory cytokines and iNOS. We attempted to determine whether transfection of an NF-B decoy into allografts could reduce NO production and ameliorate acute lung injury during allograft rejection. Methods: Left lung transplantation was performed in pairs of Brown Norway (RT1ⁿ) and Lewis (RT¹) rats. In Group NF (n=6), the allografts were flushed with 20ml of PBS solution containing a hemagglutinating virus of Japan (HVJ) liposome-ODN complex as an NF-B decoy and preserved for 60min at 4°C. A scramble decoy was used in the positive control (Group S, n=5) and simple PBS solution in the negative control (Group C, n=5). Five days after transplantation without use of immuno-suppressants, exhaled NO, gas exchange, and graft histological rejection score were determined. Results: The exhaled NO level was significantly reduced in Group NF as compared with Group S (445±162 vs 1305±123 ppb, P<0.02), while improvements in PaO2 (197±28 vs. 60±18mmHg, P<0.02) and rejection score (1.8±0.3 vs. 2.5±0.4) were also observed. There were no differences in these parameters between Groups S and C. Conclusions: Inhibition of NF-B activation in the allograft by ODN decoy transfection into the donor lung ameliorated lung injury during acute allograft rejection. Our results imply a possible therapeutic target for the inflammation process in lung transplantation clinical settings.

Key Words: Allograft lung injury • Gene Transfer • Lung transplantation • NF-B

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