Carbon monoxide–releasing molecule attenuates allograft airway rejection. (28th April 2014)

• Record Type: Journal Article
• Authors: Ohtsuka, Takashi; Kaseda, Kaoru; Shigenobu, Takao; Hato, Tai; Kamiyama, Ikuo; Goto, Taichiro; Kohno, Mitsutomo; Shimoda, Masayuki
• Is Part Of: Transplant international. Volume 27:Number 7(2014:Jul.)
• Page Start: 741
• Page End: 747
• Publication Date: 2014-04-28
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95405
• DOI: 10.1111/tri.12314
• Languages: English
• ISSNs: 0934-0874

Abstract

<abstract abstract-type="main" id="tri12314-abs-0001"> <title>Summary</title> <p>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 (<italic>P</italic> < 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 (<italic>P</italic> < 0.01) at days 14 and 21. There was also a concordant decrease in CD3<sup>+</sup> 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.</p> </abstract>