Potassium leakage primes stored erythrocytes for phosphatidylserine exposure and shedding of pro-coagulant vesicles
Potassium leakage primes stored erythrocytes for phosphatidylserine exposure and shedding of pro-coagulant vesicles
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DOI：
10.1111/bjh.12133
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发表时间：
2013-02-01
影响因子：
6.5
通讯作者：
van Bruggen, Robin
中科院分区：
文献类型：
--
作者：
Burger, Patrick;Kostova, Elena;van Bruggen, Robin
在储存期间，红细胞发生变化，在输血后改变其清除率和功能，越来越多的证据表明这些变化有助于在输血患者中观察到的并发症。将储存的红细胞在37 ℃下孵育过夜，以模拟输血后的温度。孵育后，分析红细胞损伤的几种标志物。过夜孵育后，储存的红细胞显示出增加的钾渗漏，溶血，PS暴露和囊泡形成，所有这些影响随着储存时间的增加而增加。此外，我们证明了长期储存的红细胞在过夜孵育后翻转酶活性降低，扰乱活性增加，导致PS暴露和囊泡释放。细胞内钾的减少被确定为翻转酶活性降低的原因。最后，我们提供的证据表明，红细胞可以返回到PS-阴性状态脱落的部分膜作为PS-含有囊泡，这些囊泡可以作为一个平台的凝血级联。这些研究结果表明，钾渗漏，一个众所周知的现象，延长红细胞储存，底漆红细胞PS曝光。PS暴露会导致囊泡形成，并可能对储存红细胞的输血后功能和副作用产生重要影响。
During storage, erythrocytes undergo changes that alter their clearance and function after transfusion and there is increasing evidence that these changes contribute to the complications observed in transfused patients. Stored erythrocytes were incubated overnight at 37 degrees C to mimic the temperature after transfusion. After incubation, several markers for erythrocyte damage were analysed. After overnight incubation, stored erythrocytes showed increased potassium leakage, haemolysis, PS exposure and vesicle formation, and all these effects increased with increasing storage time. Furthermore, we demonstrated that long-term stored erythrocytes develop decreased flippase activity and increased scrambling activity after overnight incubation, leading to PS exposure and the release of vesicles. Reduced intracellular potassium was identified as the cause of the decreased flippase activity. Lastly, we provide evidence that erythrocytes can return to a PS-negative state by shedding parts of their membrane as PS-containing vesicles and that these vesicles can serve as a platform for the coagulation cascade. These findings reveal that potassium leakage, a well-known phenomenon of prolonged erythrocyte storage, primes erythrocytes for PS exposure. PS exposure will lead to vesicle formation and might have an important impact on the post-transfusion function and side effects of stored erythrocytes.