Melzak Kathryn A, Uhlig Stefanie, Kirschhöfer Frank, Brenner-Weiss Gerald, Bieback Karen
Institute of Functional Interfaces, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany.
Institute for Transfusion Medicine and Immunology, Flowcore Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Transfus Med Hemother. 2018 Nov;45(6):413-422. doi: 10.1159/000490502. Epub 2018 Oct 30.
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.
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.
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.
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.
在红细胞浓缩液储存期间，使血袋保持柔软的增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP）会渗出，并可被红细胞摄取。已知DEHP对红细胞储存质量有益，但其作用的分子机制尚不清楚。
将DEHP的水悬浮液添加到缓冲液中的红细胞中。观察了5名供体红细胞的形态学效应。使用膜联蛋白A5结合的流式细胞术测量暴露的磷脂酰丝氨酸。
只要细胞悬液也足够稀释，DEHP在低至纳克/毫升的浓度下就能诱导口形细胞的形成。还形成了一些易裂解的球形细胞；裂解后，可见红细胞血影继续转变为杯状口形细胞形态。与DEHP孵育会增加暴露的磷脂酰丝氨酸，在存在钒酸盐的情况下也观察到了这种效应，钒酸盐会抑制维持膜脂质不对称性的ATP依赖性转运酶。
DEHP对红细胞形状可产生积极影响，而不仅仅是防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翻转增加介导的。
