Exacerbation of Bleomycin-Induced Injury and Fibrosis by Pneumonectomy in the Residual Lung of Mice

Toru Kakizaki, Mitsutomo Kohno, Masazumi Watanabe, Atsushi Tajima, Yotaro Izumi, Taku Miyasho, Sadatomo Tasaka, Koichi Fukunaga, Ikuro Maruyama, Akitoshi Ishizaka, Koichi Kobayashi

研究成果: Article査読

11 被引用数 (Scopus)


Background: Lung resection after induction chemotherapy and/or radiotherapy for down-staging of locally advanced lung cancer can be complicated with lethal interstitial pneumonia. We studied the effects of pneumonectomy on bleomycin-induced lung injury and fibrosis in mice. Methods: The mice underwent left pneumonectomy or a sham thoracotomy after intratracheal administration of saline or bleomycin. Lung permeability index, wet-to-dry weight ratio, histological changes, collagen contents, and concentrations of inflammatory mediators and cell counts in broncho-alveolar lavage (BAL) fluid were assessed in the residual right lung 7 d after surgery. Results: The index of capillary permeability, lung water content, and inflammatory cell counts in BAL fluid were significantly increased by pneumonectomy. These measurements were highest in the mice with both pneumonectomy and intratracheal administration of bleomycin. Similarly, fibrotic change in lung pathology, as well as an increase in lung collagen content, was most prominent in the mice exposed to both interventions. The BAL fluid concentrations of interleukin-1β, interleukin-6, RANTES, and high mobility group box 1 were significantly increased by pneumonectomy and enhanced by the additional administration of bleomycin. Conclusions: The results of this study indicate that pneumonectomy alone causes noncritical lung injury, which amplifies the inflammatory response to bleomycin and promotes lung fibrosis. Several inflammatory mediators appear to be involved in the exacerbation of bleomycin-induced lung injury and fibrosis.

ジャーナルJournal of Surgical Research
出版ステータスPublished - 2009 6月 15

ASJC Scopus subject areas

  • 外科


「Exacerbation of Bleomycin-Induced Injury and Fibrosis by Pneumonectomy in the Residual Lung of Mice」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。