输注异基因耐受性DC产生的外囊泡体引发输血相关急性肺损伤风险的研究  

The Infusion of Extracellular Vesicle Secreted by Allogeneic Tolerant Dendritic Cells Carries the Risk of Exacerbating TRALI

作　　者：高跞[1] 杨懿铭[1] 蒋雪玉[1] 谢如锋[1] 孙娟[1] 杨洁[1] GAO Li;YANG Yiming;JIANG Xueyu;XIE Rufeng;SUN Juan;YANG Jie(Shanghai Blood Center,Shanghai 200051)

机构地区：[1]上海市血液中心输血研究所血液工程学科,上海200051

出　　处：《临床输血与检验》2024年第5期592-597,共6页Journal of Clinical Transfusion and Laboratory Medicine

基　　金：上海市卫生健康委员会面上项目(No.201940111,No.202140008);上海市血液中心科技基金项目(No.03J2202-11)资助。

摘　　要：目的探讨利用耐受性的树突状细胞(dendritic cell,DC)分泌的细胞外囊泡(extracellular vesicles,EVs)干预感染后输血相关急性肺损伤(transfusion-related acute lung injury,TRALI)策略的风险。方法体外诱导小鼠骨髓来源的DC细胞用雷帕霉素处理诱导成耐受性DC,收集其培养上清,通过梯度离心法收获EVs。利用LPS和抗H2Kd抗体诱导Balb/c小鼠为TRALI疾病模型,并尝试用同基因的雷帕霉素-DC或者异基因的雷帕霉素-DC分泌的EV对TRALI小鼠进行干预,观察并记录发病小鼠的一系列数据。结果与TRALI发病组相比,使用雷帕霉素处理后的同基因耐受性DC对TRALI发病小鼠进行干预后,小鼠的死亡率显著下降。当用异基因耐受性DC(雷帕霉素处理后)产生的EVs进行干预组的肺湿/干比率、胸腔积液和体温与仅用LPS和H2Kd抗体处理组小鼠没有显著性差异。来源于耐受性细胞异基因EVs与LPS联合后不诱发小鼠的TRALI,但是EVs干预后的死亡率与注射浓度呈正相关。结论雷帕霉素处理后的同基因DC对感染后TRALI具有保护作用,并且该耐受细胞的异基因细胞外囊泡联合LPS后本身并不引起呼吸窘迫现象,当这种异基因外囊泡体输注联合抗白细胞抗体时,却加重了TRALI的死亡风险。本研究数据提示,异基因外囊泡体的应用与输血同时进行时,也许可能会加重TRALI死亡风险。Objective To explore the feasibility and risks of using extracellular vesicles(EVs)secreted by tolerant dendritic cells(DC)to intervene in transfusion-related acute lung injury(TRALI).Methods Mouse bone marrow-derived DC cells were induced in vitro to become tolerant DCs by treatment with rapamycin,and the culture supernatant was collected and EVs were harvested by gradient centrifugation.Balb/c mice were induced into a TRALI disease model using LPS and anti-H2Kd antibodies,and EVs secreted by isogenic rapamycin-DCs or allogenic rapamycin-DCs were used to intervene in TRALI mice,and a series of data of diseased mice were observed and recorded.Results Compared with the TRALI onset group,after using rapamycin-treated tolerant DCs to intervene in TRALI onset mice,the mortality rate of the mice was significantly reduced.Unexpectedly,intervention with EVs generated from allogeneic tolerant DC(after rapamycin treatment)aggravated the mortality of TRALI.Despite EVs intervention,lung wet-to-dry ratio,pleural effusion and body temperature were not significantly different from those in mice treated with LPS and H2Kd antibodies alone.However,the mortality rate after EVs intervention was positively correlated with the injection concentration,even though the allogeneic vesicles were derived from tolerant cells and did not induce TRALI in mice when combined with LPS.Conclusion Allogeneic extracellular vesicle infusion combined with anti-leukocyte antibodies will increase the risk of death in TRALI,even though autologous DC has a protective effect on TRALI.Also,the allogeneic extracellular vesicles only combined with LPS does not cause respiratory distress.The data from this study suggest that we need to pay more attention on the risk of TRALI aggravated by the application of allogeneic EV therapies.

关 键 词：输血相关急性肺损伤 TRALI小鼠模型 树突状细胞 细胞外囊泡体 

分 类 号：R457[医药卫生—治疗学]