Carbon monoxide-releasing molecule attenuates allograft airway rejection.

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.

• Authors: Takashi Ohtsuka, Kaoru Kaseda, Takao Shigenobu, Tai Hato, Ikuo Kamiyama, Taichiro Goto, Mitsutomo Kohno, Masayuki Shimoda
• Journal: Transplant international : official journal of the European Society for Organ Transplantation (Transpl Int) Vol. 27 Issue 7 Pg. 741-7 (Jul 2014) ISSN: 1432-2277 [Electronic] Switzerland
• PMID: 24628975 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Steunstichting ESOT.

Chemical References

• Organometallic Compounds
• tricarbonyldichlororuthenium (II) dimer
• Carbon Monoxide

Topics

• Allografts
• Animals
• Bronchiolitis Obliterans (etiology)
• Carbon Monoxide (metabolism)
• Lung Transplantation (adverse effects)
• Male
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Organometallic Compounds (pharmacology)
• Trachea (transplantation)