Carbon monoxide-releasing molecule attenuates allograft airway rejection

Takashi Ohtsuka, Kaoru Kaseda, Takao Shigenobu, Tai Hato, Ikuo Kamiyama, Taichiro Goto, Mitsutomo Kohno, Masayuki Shimoda

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Acute rejection after lung transplantation is the main risk factor for the development of bronchiolitis obliterans (BO). Carbon monoxide (CO) can provide anti-inflammatory effects and may serve to limit tissue injury in airway transplant. Here, we tested the ability of carbon monoxide releasing molecule-2 (CORM-2) to prevent airway rejection. Tracheal grafts from BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Experimental groups were treated with multiple doses of CORM-2. Histopathological evaluation of luminal obliteration was blindly reviewed. Immunohistochemistry and real-time RT-PCR analyses were performed. Allografts treated with CORM-2 revealed a striking reduction of thickening in epithelial and subepithelial airway layers (P < 0.01) at day 7 in orthotopic trachea transplantation model compared with allografts treated with vehicle. In heterotopic trachea transplantation model, CORM-2 treated allografts showed a reduction of luminal obliteration (P < 0.01) at days 14 and 21. There was also a concordant decrease in CD3+ lymphocytes and macrophages in CORM-2 treated allografts. IFN-γ, IL-2 and IL17A mRNA expressions were reduced dramatically by systemic administration of CORM-2. These data implicate CORM-2-derived CO has an important protective function in experimental BO, and may represent a target for the therapeutic intervention of chronic lung allograft rejection.

Original languageEnglish
Pages (from-to)741-747
Number of pages7
JournalTransplant International
Volume27
Issue number7
DOIs
Publication statusPublished - 2014 Jul

Keywords

  • airway obstruction
  • carbon monoxide
  • lung transplantation

ASJC Scopus subject areas

  • Transplantation

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