Qadri Syed M, Chen Deborah, Schubert Peter, Perruzza Darian L, Bhakta Varsha, Devine Dana V, Sheffield William P
Centre for Innovation, Canadian Blood Services, McMaster University, Hamilton, Ontario, Canada.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Transfusion. 2017 Mar;57(3):661-673. doi: 10.1111/trf.13959. Epub 2016 Dec 26.
Pathogen reduction treatment using riboflavin and ultraviolet light illumination (Mirasol) effectively reduces the risk of transfusion-transmitted infections. This treatment is currently licensed for only platelets and plasma products, while its application to whole blood (WB) to generate pathogen-inactivated red blood cells (RBCs) is under development. RBC storage lesion, constituting numerous morphologic and biochemical changes, influences RBC quality and limits shelf life. Stored RBCs further show enhanced susceptibility to RBC programmed cell death (eryptosis) characterized by increased cytosolic Ca -provoked membrane phosphatidylserine (PS) externalization.
Using a "pool-and-split" approach, we examined multiple variables of RBC storage lesion and eryptosis in RBC units, derived from Mirasol-treated or untreated WB, after 4 to 42 days of storage, under blood bank conditions.
In comparison to untreated RBC units, Mirasol treatment significantly altered membrane microvesiculation, supernatant hemoglobin, osmotic fragility, and intracellular adenosine triphosphate levels but did not influence membrane CD47 expression and 2,3-diphosphoglycerate levels. Mirasol-treated RBCs showed significantly higher PS exposure after 42, but not after not more than 21, days of storage, which was accompanied by enhanced cytosolic Ca activity, ceramide abundance, and oxidative stress, but not p38 kinase activation. Mirasol treatment significantly augmented PS exposure, Ca entry, and protein kinase C activation after energy depletion, a pathophysiologic cell stressor. Mirasol-treated RBCs were, however, more resistant to cell shrinkage.
Prolonged storage of Mirasol-treated RBCs significantly increases the proportion of eryptotic RBCs, while even short-term storage enhances the susceptibility of RBCs to stress-induced eryptosis, which could reduce posttransfusion RBC recovery in patients.
使用核黄素和紫外线照射进行病原体灭活处理（Mirasol）可有效降低输血传播感染的风险。该处理目前仅获许可用于血小板和血浆制品，而将其应用于全血（WB）以生成病原体灭活的红细胞（RBC）的研究正在进行中。红细胞储存损伤包括众多形态学和生化变化，会影响红细胞质量并限制其保质期。储存的红细胞还表现出对红细胞程序性细胞死亡（红细胞凋亡）的易感性增强，其特征是细胞溶质钙增加引发膜磷脂酰丝氨酸（PS）外化。
采用“合并与分割”方法，我们在血库条件下，对储存4至42天的、来自经Mirasol处理或未处理的全血的红细胞单位中的红细胞储存损伤和红细胞凋亡的多个变量进行了检测。
与未处理的红细胞单位相比，Mirasol处理显著改变了膜微泡形成、上清液血红蛋白、渗透脆性和细胞内三磷酸腺苷水平，但不影响膜CD47表达和2,3 - 二磷酸甘油酸水平。Mirasol处理的红细胞在储存42天后（而非不超过21天后）显示出显著更高的PS暴露，这伴随着细胞溶质钙活性增强、神经酰胺丰度增加和氧化应激，但不伴有p38激酶激活。在能量耗竭（一种病理生理细胞应激源）后，Mirasol处理显著增加了PS暴露、钙内流和蛋白激酶C激活。然而，Mirasol处理的红细胞对细胞收缩更具抵抗力。
Mirasol处理的红细胞长期储存会显著增加红细胞凋亡的比例，而即使短期储存也会增强红细胞对应激诱导的红细胞凋亡的易感性，这可能会降低患者输血后红细胞的回收率。
