Intramuscular gene transfer of interleukin-10 reduces neutrophil recruitment and ameliorates lung graft ischemia-reperfusion injury

Benjamin D. Kozower, Samer A. Kanaan, Tsutomu Tagawa, Takashi Suda, Kathleen Grapperhaus, Niccolo Daddi, Erika C. Crouch, Claire M. Doerschuk, G. Alexander Patterson

研究成果: Article査読

23 被引用数 (Scopus)

抄録

Interleukin-10 (IL-10) has potent anti-inflammatory properties but its direct effects on neutrophil trafficking in lung transplant ischemia-reperfusion (I/R) injury are unknown. This study was performed to determine if recipient intramuscular IL-10 gene transfer reduces neutrophil infiltration in lung isografts and ameliorates I/R injury. Twenty-four hours before transplantation, recipient rodents received intramuscular injection with 1 × 1010 plaque-forming units (pfu) adenovirus encoding human IL-10 (hIL-10), 1 × 1010 pfu adenovirus control encoding p-galactosidase, or saline. Gene expression in muscle and plasma was confirmed. Lung grafts were harvested, stored at 4°C for 18h, and assessed 24h after transplantation. Peak muscle and plasma expression of hIL-10 was achieved 24h after gene transfer and returned to baseline by 7 days (p <0.05 vs. controls). Gene transfer of hIL-10 reduced neutrophil sequestration and emigration in lung grafts as measured by morphometry and myeloperoxidase activity (p <0.03 vs. controls). Furthermore, hIL-10 improved graft oxygenation and reduced lung edema (p <0.01 vs. controls). Intramuscular gene transfer of hIL-10 releases hIL-10 protein into plasma and reduces neutrophil sequestration and emigration in lung isografts. This is associated with a reduction in I/R injury with improved isograft oxygenation and reduced tissue edema. Intramuscular gene transfer may be a useful strategy to reduce clinical I/R injury.

本文言語English
ページ(範囲)837-842
ページ数6
ジャーナルAmerican Journal of Transplantation
2
9
DOI
出版ステータスPublished - 10-2002
外部発表はい

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 移植
  • 薬理学(医学)

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