Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post-lung transplant
Transplant Division, Department of Surgery
Analytical, Diagnostic and Therapeutic Techniques and Equipment | Immunology and Infectious Disease | Surgery
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.
animal models, murine, basic (laboratory) research/science, complement biology, immunobiology, immunosuppression/immune modulation, ischemia reperfusion injury (IRI), lung transplantation/pulmonology
DOI of Published Version
Am J Transplant. 2018 Oct;18(10):2417-2428. doi: 10.1111/ajt.14717. Epub 2018 Apr 10. Link to article on publisher's site
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Cheng, Qi; Patel, Kunal; Lei, Biao; Rucker, Lindsay; Allen, D. Patterson; Zhu, Peng; Vasu, Chentha; Martins, Paulo N.A.; Goddard, Martin; Nadig, Satish N.; and Atkinson, Carl, "Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post-lung transplant" (2018). Surgery Publications and Presentations. 171.