Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post-lung transplant
| Autor: | Chentha Vasu, Peng Zhu, Qi Cheng, Carl Atkinson, Satish N. Nadig, Martin Goddard, Lindsay Rucker, Paulo N. Martins, Kunal Patel, Biao Lei, D. Patterson Allen |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Graft Rejection Brain Death medicine.medical_treatment Context (language use) 030230 surgery Article 03 medical and health sciences Mice 0302 clinical medicine Immune system Administration Inhalation medicine Immunology and Allergy Lung transplantation Animals Pharmacology (medical) Transplantation Mice Inbred BALB C Lung biology business.industry Tissue Donors Complement system Receptors Complement Mice Inbred C57BL 030104 developmental biology Cytokine medicine.anatomical_structure Reperfusion Injury Immunology biology.protein C3a receptor business Lung Transplantation |
| Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 18(10) |
| ISSN: | 1600-6143 |
| Popis: | Donor brain death (BD) is an inherent part of lung transplantation (LTx) and a key contributor to ischemia-reperfusion injury (IRI). Complement activation occurs as a consequence of BD in other solid organ Tx and exacerbates IRI, but the role of complement in LTx has not been investigated. Here, we investigate the utility of delivering nebulized C3a receptor antagonist (C3aRA) pretransplant to BD donor lungs in order to reduce post-LTx IRI. BD was induced in Balb/c donors, and lungs nebulized with C3aRA or vehicle 30 minutes prior to lung procurement. Lungs were then cold stored for 18 hours before transplantation into C57Bl/6 recipients. Donor lungs from living donors (LD) were removed and similarly stored. At 6 hours and 5 days post-LTx, recipients of BD donor lungs had exacerbated IRI and acute rejection (AR), respectively, compared to recipients receiving LD lungs, as determined by increased histopathological injury, immune cells, and cytokine levels. A single pretransplant nebulized dose of C3aRA to the donor significantly reduced IRI as compared to vehicle-treated BD donors, and returned IRI and AR grades to that seen following LD LTx. These data demonstrate a role for complement inhibition in the amelioration of IRI post-LTx in the context of donor BD. |
| Databáze: | OpenAIRE |
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