Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain-death induced immunological injury post-lung transplant
Authors
Cheng, QiPatel, Kunal
Lei, Biao
Rucker, Lindsay
Allen, D. Patterson
Zhu, Peng
Vasu, Chentha
Martins, Paulo N.A.
Goddard, Martin
Nadig, Satish N.
Atkinson, Carl
UMass Chan Affiliations
Transplant Division, Department of SurgeryDocument Type
Journal ArticlePublication Date
2018-10-01Keywords
animal modelsmurine
basic (laboratory) research/science
complement biology
immunobiology
immunosuppression/immune modulation
ischemia reperfusion injury (IRI)
lung transplantation/pulmonology
Analytical, Diagnostic and Therapeutic Techniques and Equipment
Immunology and Infectious Disease
Surgery
Metadata
Show full item recordAbstract
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.Source
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
DOI
10.1111/ajt.14717Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49745PubMed ID
29504277Related Resources
ae974a485f413a2113503eed53cd6c53
10.1111/ajt.14717