Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, China.
Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, China.
Xenotransplantation. 2021 May;28(3):e12657. doi: 10.1111/xen.12657. Epub 2020 Oct 28.
Liver xenotransplantation (LXT) is greatly impeded by severe thrombocytopenia, anemia, and coagulopathy. Hepatic phagocytic cells are thought to play an important role in LXT-induced thrombocytopenia and anemia. In this study, we investigated whether the lack of recipient CD47-donor SIRPα interaction, which is known to induce xenograft rejection by macrophages, exacerbates platelet and RBC depletion following LXT. We first addressed this question in the absence of anti-donor immune responses using a syngeneic mouse liver transplantation (LT) model. Neither wild-type (WT) nor CD47KO B6 mice developed thrombocytopenia following LT from WT B6 donors. Although a moderate decline in RBCs was detected following LT, there was no significant difference in RBC counts between WT and CD47KO recipients. Because mouse CD47 is cross-reactive with rat SIRPα, we then compared thrombocytopenia and anemia between WT and CD47KO mice following rat LXT. Unlike syngeneic mouse LT, significant thrombocytopenia and anemia were detected following rat LXT. However, the severities of both platelet and RBC depletions were comparable between WT and CD47KO recipients. Furthermore, WT and CD47KO recipients showed a similar extent of early platelet activation. Our results indicate that CD47-SIRPα signaling does not significantly affect the loss of platelets or RBCs following LXT, suggesting that the limited cross-reactivity between recipient CD47 and donor SIRPα is not a significant risk factor for LXT-induced thrombocytopenia and anemia.
肝异种移植（LXT）受到严重血小板减少症、贫血和凝血功能障碍的严重阻碍。肝吞噬细胞被认为在 LXT 诱导的血小板减少症和贫血中发挥重要作用。在这项研究中，我们研究了是否缺乏受者 CD47-供体 SIRPα 相互作用会加剧 LXT 后血小板和 RBC 的耗竭，已知该相互作用会诱导异种移植物排斥反应。我们首先在不存在抗供体免疫反应的情况下使用同基因小鼠肝移植（LT）模型来解决这个问题。来自 WT B6 供体的 WT 和 CD47KO B6 小鼠在 LT 后均未发生血小板减少症。尽管 LT 后 RBC 计数略有下降，但 WT 和 CD47KO 受者的 RBC 计数没有显著差异。由于小鼠 CD47 与大鼠 SIRPα 交叉反应，我们随后比较了 WT 和 CD47KO 小鼠在大鼠 LXT 后的血小板减少症和贫血。与同基因小鼠 LT 不同，大鼠 LXT 后明显出现血小板减少症和贫血。然而，WT 和 CD47KO 受者的血小板和 RBC 耗竭程度相当。此外，WT 和 CD47KO 受者的早期血小板激活程度相似。我们的结果表明，CD47-SIRPα 信号在 LXT 后不会显著影响血小板或 RBC 的丢失，这表明受体 CD47 与供体 SIRPα 之间有限的交叉反应不是 LXT 诱导的血小板减少症和贫血的重要危险因素。
