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- Title
Carbon monoxide-releasing molecule attenuates allograft airway rejection.
- Authors
Ohtsuka, Takashi; Kaseda, Kaoru; Shigenobu, Takao; Hato, Tai; Kamiyama, Ikuo; Goto, Taichiro; Kohno, Mitsutomo; Shimoda, Masayuki
- 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 C57 BL/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.
- Subjects
CARBON monoxide; HOMOGRAFTS; GRAFT rejection; BRONCHIOLITIS; IMMUNOHISTOCHEMISTRY; REVERSE transcriptase polymerase chain reaction; THERAPEUTICS
- Publication
Transplant International, 2014, Vol 27, Issue 7, p741
- ISSN
0934-0874
- Publication type
Article
- DOI
10.1111/tri.12314