Department of Surgery, Institute of Organ Transplantation, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Am J Transplant. 2018 Oct;18(10):2417-2428. doi: 10.1111/ajt.14717. Epub 2018 Apr 10.
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.
供体脑死亡（BD）是肺移植（LTx）的固有部分，也是缺血再灌注损伤（IRI）的主要原因。在其他实体器官 Tx 中，BD 会导致补体激活，并加重 IRI，但补体在 LTx 中的作用尚未得到研究。在这里，我们研究了在 BD 供体肺移植前给予雾化 C3a 受体拮抗剂（C3aRA）的效用，以减少移植后的 IRI。在进行肺移植前 30 分钟，对 Balb/c 供体进行 BD 诱导，并对供体肺进行 C3aRA 或载体雾化。然后将肺在冷储存 18 小时，然后移植到 C57Bl/6 受体中。从活体供体（LD）中取出供体肺，并进行类似的储存。在 LTx 后 6 小时和 5 天，与接受 LD 肺的受体相比，接受 BD 供体肺的受体分别出现了更严重的 IRI 和急性排斥反应（AR），这可以通过增加组织病理学损伤、免疫细胞和细胞因子水平来确定。与接受载体治疗的 BD 供体相比，单次移植前给予供体雾化 C3aRA 可显著减轻 IRI，并使 IRI 和 AR 分级恢复到接受 LD LTx 后的水平。这些数据表明，补体抑制在 BD 供体背景下可改善 LTx 后的 IRI。
