Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation, and function.

Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation, and function.
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DOI:
10.3109/09537104.2014.898178
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发表时间:
2015
期刊:
影响因子:
3.3
通讯作者:
Provost P
Provost P
中科院分区:
医学3区
文献类型:
--
作者:
Osman A;Hitzler WE;Meyer CU;Landry P;Corduan A;Laffont B;Boilard E;Hellstern P;Vamvakas EC;Provost P

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血小板病原体减少(PR)系统基于化学诱导的核酸交联和失活,有可能防止感染性病原体的输血传播,但在一些临床研究中可能会增加临床上显着的出血。在这里,我们记录了 PR 系统对血库中储存的血小板 microRNA 和 mRNA 水平的影响,并评估了它们对血小板活化和功能的影响。与接受伽马射线照射或储存在添加剂溶液中的血小板不同,与储存在血浆中的血小板相比,用 Intercept(amotosalen + 紫外线-A [UVA] 光)处理的血小板表现出我们监测的 11 种 microRNA 中的 6 种和 3 种抗凋亡 mRNA(Bcl-xl 和 Clusterin)中的 2 种的水平显着降低。 Mirasol(核黄素 + UVB 光)治疗血小板不会产生这些效果。 PR 既不影响血小板 microRNA 合成或功能,也不诱导 microRNA 大小的内源性血小板 RNA 种类的交联。然而,Intercept 诱导的血小板 microRNA 水平降低与血小板活化 (p<0.05) 和 ADP 血小板聚集反应受损 (p<0.05) 相关。这些结果表明 Intercept 治疗可能会诱导血小板活化,导致血小板释放 microRNA 和 mRNA。继发于拦截的血小板核酸减少的临床意义仍有待确定。
Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen + ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol (riboflavin + UVB light) treatment of platelets did not produce these effects. PR neither affected platelet microRNA synthesis or function nor induced cross-linking of microRNA-sized endogenous platelet RNA species. However, the reduction in the platelet microRNA levels induced by Intercept correlated with the platelet activation (p < 0.05) and an impaired platelet aggregation response to ADP (p < 0.05). These results suggest that Intercept treatment may induce platelet activation, resulting in the release of microRNAs and mRNAs from platelets. The clinical implications of this reduction in platelet nucleic acids secondary to Intercept remain to be established.
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