Background: During storage of red blood cell (RBC) concentrates, the plasticizer di-2-ethylhexylphthalate (DEHP) that keeps the blood bags soft leaches out and can be taken up by the RBCs. DEHP is known to be beneficial for the RBC storage quality, but the molecular mechanisms of the action are unknown. Methods: Aqueous suspensions of DEHP were added to RBCs in buffer. The morphological effects were observed on RBCs from 5 donors. Flow cytometry with annexin A5 binding was used to measure the exposed phosphatidylserine. Results: DEHP induced the formation of stomatocytes at concentrations as low as ng/ml, provided that the cell suspension was also sufficiently dilute. Some spherocytes, which were susceptible to lysis, were also formed; after lysis, RBC ghosts were seen to continue the transition to the cup-shaped stomatocyte form. Incubation with DEHP increased the exposed phosphatidylserine, an effect that was also observed in the presence of vanadate, which inhibits the ATP-dependent translocases that maintain the membrane's lipid asymmetry. Conclusions: DEHP can have an active effect on RBC shape, instead of just preventing the storage-related shape changes. The effect appears to be mediated by increased flip-flop of lipids between the leaflets of the RBC membrane.

中文翻译：

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血袋增塑剂 Di-2-Ethylhexylphthalate 导致红细胞形成口细胞，可能通过诱导脂质触发器

背景：在红细胞 (RBC) 浓缩物的储存过程中，使血袋保持柔软的增塑剂邻苯二甲酸二乙基己酯 (DEHP) 会渗出并被红细胞吸收。众所周知，DEHP 对 RBC 的储存质量有益，但其作用的分子机制尚不清楚。方法：将 DEHP 的水性悬浮液添加到缓冲液中的红细胞中。在来自 5 个供体的红细胞上观察到形态学影响。具有膜联蛋白 A5 结合的流式细胞术用于测量暴露的磷脂酰丝氨酸。结果：如果细胞悬液也足够稀释，DEHP 可在低至 ng/ml 的浓度下诱导形成口细胞。还形成了一些易裂解的球形红细胞；裂解后，可见红细胞幽灵继续转变为杯形口细胞形式。与 DEHP 一起孵育会增加暴露的磷脂酰丝氨酸，在钒酸盐存在的情况下也观察到这种效应，钒酸盐会抑制维持膜脂质不对称的 ATP 依赖性转位酶。结论：DEHP 可以对 RBC 形状产生积极影响，而不仅仅是阻止与储存相关的形状变化。这种效应似乎是由红细胞膜小叶之间脂质的翻转增加所介导的。