Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity
Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity
复制标题
DOI：
10.1182/bloodadvances.2018021931
复制
发表时间：
2018-09-25
期刊：
影响因子：
7.5
通讯作者：
Muszynski, Jennifer A.
中科院分区：
文献类型：
--
作者：
Almizraq, Ruqayyah J.;Norris, Philip J.;Muszynski, Jennifer A.
输注红细胞浓缩物 (RCC) 会增加不良后果的风险，这可能受到不同血液制造方法和细胞外囊泡 (EV) 存在的影响。我们研究了不同制造方法对溶血、残留细胞、细胞源性 EV 的影响以及对单核细胞活性的免疫调节作用。对使用全血过滤 (WBF)、红细胞过滤 (RCF)、单采血液分离 (AD) 和全血分离 (WBD) 方法生产的 32 个 RCC 单位进行了检查（每种方法 n = 8）。在新鲜和储存的上清液中评估了 RCC 上清液中残留的血小板和白细胞 (WBC) 以及 EV 的浓度、细胞来源和特征。通过量化体外输血模型中单核细胞细胞因子的产生能力来评估 RCC 上清液的免疫调节活性。 RCF 单位产生的血小板和 WBC 衍生的 EV 数量最低，而血小板 EV 数量最高的是 AD（第 5 天）和 WBD（第 42 天）。所有测试的上清液中小 EV 的数量（= 200 nm），并且小 EV 的最高水平在 AD 单位中。免疫调节活性是混合的，有炎症和免疫抑制作用的证据。暴露于新鲜的WBF或过期的WBD上清液后，单核细胞产生更多的炎性白细胞介素8。暴露于 AD 和 WBD RCC 的上清液可抑制单核细胞脂多糖诱导的细胞因子产生。制造方法显着影响 RCC 单位 EV 特性，并与 RCC 上清液的免疫调节作用相关，这可能会影响 RCC 的质量和安全性。
Transfusion of red cell concentrates (RCCs) is associated with increased risk of adverse outcomes that maybe affected by different blood manufacturing methods and the presence of extracellular vesicles (EVs). We investigated the effect of different manufacturing methods on hemolysis, residual cells, cell-derived EVs, and immunomodulatory effects on monocyte activity. Thirty-two RCC units produced using whole blood filtration (WBF), red cell filtration (RCF), apheresis-derived (AD), and whole blood-derived (WBD) methods were examined (n = 8 per method). Residual platelet and white blood cells (WBCs) and the concentration, cell of origin, and characterization of EVs in RCC supernatants were assessed in fresh and stored supernatants. Immunomodulatory activity of RCC supernatants was assessed by quantifying monocyte cytokine production capacity in an in vitro transfusion model. RCF units yielded the lowest number of platelet and WBC-derived EVs, whereas the highest number of platelet EVs was in AD (day 5) and in WBD (day 42). The number of small EVs (= 200 nm) in all tested supernatants, and the highest level of small EVs were in AD units. Immunomodulatory activity was mixed, with evidence of both inflammatory and immunosuppressive effects. Monocytes produced more inflammatory interleukin-8 after exposure to fresh WBF or expired WBD supernatants. Exposure to supernatants from AD and WBD RCC suppressed monocyte lipopolysaccharide-induced cytokine production. Manufacturing methods significantly affect RCC unit EV characteristics and are associated with an immunomodulatory effect of RCC supernatants, which may affect the quality and safety of RCCs.