TY - JOUR
T1 - Endobronchial gene transfer of soluble type I interleukin-1 receptor ameliorates lung graft ischemia-reperfusion injury
AU - Tagawa, Tsutomu
AU - Dharmarajan, Sekhar
AU - Hayama, Makio
AU - Ishiyama, Takaaki
AU - Suda, Takashi
AU - Itano, Hideki
AU - Patterson, G. Alexander
N1 - Funding Information:
The authors thank Dr Paul D. Robbins, Departments of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, for kindly providing adenovirus encoding sIL-1RI-Ig. The authors thank Richard B. Schuessler, PhD, for his statistical advice. They also thank Kathleen Grapperhaus for technical assistance and Dawn Schuessler and Mary Ann Kelly for secretarial support. This work was supported by National Institutes of Health Grant 1 RO1 HL41281 (Dr Patterson) and individual National Institutes of Health-NRSA Grant 1 F32 HL0746867–01 (Dr Dharmarajan).
PY - 2004/12
Y1 - 2004/12
N2 - Soluble type I interleukin-1 receptor is a competitive inhibitor of interleukin-1 and may reduce its proinflammatory actions. The objective of this experiment was to demonstrate that endobronchial gene transfer of soluble type I interleukin-1 receptor IgG to donor lung grafts reduces posttransplant ischemia-reperfusion injury. All experiments utilized an orthotopic left lung isograft transplant model. Donors were divided into three groups (n = 6 each) for endobronchial transfection: group I received 2 × 10 7 plaque-forming units of adenovirus encoding soluble type I interleukin-1 receptor IgG; group II received 2 × 10 7 plaque-forming units of nonfunctional control adenovirus encoding β-galactosidase; and group III received 0.1 mL of saline. Left lungs were harvested 24 hours after transfection and stored for 18 hours before transplantation. Graft function was assessed 24 hours after reperfusion using three measurements: isolated graft oxygenation, wet-to-dry lung weight ratio, and tissue myeloperoxidase activity. Transgene expression of soluble type I interleukin-1 receptor IgG was also evaluated using enzyme-linked immunosorbent assay and immunohistochemistry. Isolated graft arterial oxygenation was significantly improved in group I compared with groups II and III (281.8 ± 134.8 versus 115.7 ± 121.5 and 88.0 ± 58.9 mm Hg, p = 0.0197 and p = 0.0081, respectively). Myeloperoxidase activity was also significantly reduced in group I compared with groups II and III (0.083 ± 0.044 versus 0.155 ± 0.043 and 0.212 ± 0.079 optical density units per minute per milligram protein, p = 0.0485 and p = 0.0016, respectively). Expression of soluble type I interleukin-1 receptor IgG was detected only in lungs from group I. Endobronchial gene transfer of soluble type I interleukin-1 receptor IgG to donor lung grafts subjected to prolonged cold ischemia ameliorates ischemia-reperfusion injury by improving graft oxygenation and reducing lung edema and neutrophil sequestration.
AB - Soluble type I interleukin-1 receptor is a competitive inhibitor of interleukin-1 and may reduce its proinflammatory actions. The objective of this experiment was to demonstrate that endobronchial gene transfer of soluble type I interleukin-1 receptor IgG to donor lung grafts reduces posttransplant ischemia-reperfusion injury. All experiments utilized an orthotopic left lung isograft transplant model. Donors were divided into three groups (n = 6 each) for endobronchial transfection: group I received 2 × 10 7 plaque-forming units of adenovirus encoding soluble type I interleukin-1 receptor IgG; group II received 2 × 10 7 plaque-forming units of nonfunctional control adenovirus encoding β-galactosidase; and group III received 0.1 mL of saline. Left lungs were harvested 24 hours after transfection and stored for 18 hours before transplantation. Graft function was assessed 24 hours after reperfusion using three measurements: isolated graft oxygenation, wet-to-dry lung weight ratio, and tissue myeloperoxidase activity. Transgene expression of soluble type I interleukin-1 receptor IgG was also evaluated using enzyme-linked immunosorbent assay and immunohistochemistry. Isolated graft arterial oxygenation was significantly improved in group I compared with groups II and III (281.8 ± 134.8 versus 115.7 ± 121.5 and 88.0 ± 58.9 mm Hg, p = 0.0197 and p = 0.0081, respectively). Myeloperoxidase activity was also significantly reduced in group I compared with groups II and III (0.083 ± 0.044 versus 0.155 ± 0.043 and 0.212 ± 0.079 optical density units per minute per milligram protein, p = 0.0485 and p = 0.0016, respectively). Expression of soluble type I interleukin-1 receptor IgG was detected only in lungs from group I. Endobronchial gene transfer of soluble type I interleukin-1 receptor IgG to donor lung grafts subjected to prolonged cold ischemia ameliorates ischemia-reperfusion injury by improving graft oxygenation and reducing lung edema and neutrophil sequestration.
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U2 - 10.1016/j.athoracsur.2004.06.008
DO - 10.1016/j.athoracsur.2004.06.008
M3 - Article
C2 - 15561003
AN - SCOPUS:9344231391
SN - 0003-4975
VL - 78
SP - 1932
EP - 1939
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 6
ER -