Importance of tumor necrosis factor-α cleavage process in post-transplantation lung injury in rats

Taichiro Goto, Akitoshi Ishizaka, Fujio Kobayashi, Mitsutomo Kohno, Makoto Sawafuji, Sadatomo Tasaka, Eiji Ikeda, Yasunori Okada, Ikuro Maruyama, Koichi Kobayashi

研究成果: Article査読

34 被引用数 (Scopus)


Tumor necrosis factor-α (TNF-α) has two forms with apparently different biological activities: a membrane-associated form and a soluble form. TNF-α-converting enzyme (TACE) mediates a cleavage of membrane-associated TNF-α to induce its bioactive soluble form. We hypothesized that inhibition of TACE might prevent TNF-α-induced tissue injury while preserving the benefits of TNF-α. In this study, we evaluated the role of TACE in acute inflammation using an inhibitor of the enzyme in a rat model of lung transplantation. Inbred Lewis rats underwent left lung isotransplantation, and the donor lungs were kept in Euro-Collins solution with or without the inhibitor. After 6 hours of ischemia, the left lung was transplanted into the recipient rat and reperfused for 4 hours. Inhibition of TACE significantly attenuated endothelial and alveolar septal damage, as assessed by radiolabeled albumin leakage after transplantation. The inhibition also attenuated neutrophil accumulation in the alveolar space and other histopathologic findings, including intercellular adhesion molecule-1 expression. In addition, significantly lower levels of monocyte chemotactic protein-1, cytokine-induced neutrophil chemoattractant-1, high mobility group box-1, and soluble epithelial cadherin and decreased neutrophil elastase activity were observed in bronchoalveolar lavage fluid from the rats treated with the inhibitor. We conclude that TACE mediates a critical step in the development of post-transplantation lung injury.

ジャーナルAmerican journal of respiratory and critical care medicine
出版ステータスPublished - 2004 12月 1

ASJC Scopus subject areas

  • 呼吸器内科
  • 集中医療医学


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