EV Group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Biocenter 1, Viikinkaari 9, 00790 Helsinki, Finland; Finnish Red Cross Blood Service, Kivihaantie 7, 00310 Helsinki, Finland.
Finnish Red Cross Blood Service, Kivihaantie 7, 00310 Helsinki, Finland; Helsinki University Lipidomics Unit, Helsinki Institute for Life Science (HiLIFE), Biocenter 3, Viikinkaari 1, 00790 Helsinki, Finland.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Aug;1864(8):1168-1182. doi: 10.1016/j.bbalip.2019.03.011. Epub 2019 Apr 10.
Platelets are collected for transfusion to patients with different haematological disorders, and for logistical reasons, platelets are stored as concentrates. Despite carefully controlled conditions, platelets become activated during storage, and platelet concentrates (PlaCs) may cause adverse inflammatory reactions in recipients. The time-dependent changes in the lipidome of clinical PlaCs, platelets isolated from PlaCs, and extracellular vesicles (EVs) thereof were examined by mass spectrometry. The relative amount of arachidonic acid containing glycerophospholipids, especially those in the phosphatidylethanolamine and phosphatidylserine classes during storage, but the relative amount of other polyunsaturated fatty acid containing glycerophospholipids remained stable in all sample types. These changes were not directly translated to lipid mediator (LM) profile since the levels of arachidonic acid-derived proinflammatory LMs were not specifically elevated. Instead, several monohydroxy pathway markers and functionally relevant LMs, both proinflammatory and proresolving, were detected in the PlaCs and the EVs, and some representatives of both kind clearly accumulated during storage. By Western blot, the key enzymes of these pathways were shown to be present in platelets, and in many cases, EVs. Since the EVs were enriched in the fatty acid precursors of LMs in their (phospholipid) membranes, harboured LM-producing enzymes, contained the related monohydroxy pathway markers, and secreted the final LM products, PlaC-derived EVs could participate in the regulation of inflammation and healing, and thereby aid the platelets in exerting their essential physiological functions.
血小板被收集用于输注给患有不同血液疾病的患者,由于物流原因,血小板以浓缩物的形式储存。尽管条件得到了精心控制,但在储存过程中血小板会被激活,血小板浓缩物(PlaC)可能会在受者中引起不良反应的炎症反应。通过质谱法研究了临床 PlaC、从 PlaC 中分离出的血小板以及其中的细胞外囊泡(EV)的脂质组随时间的变化。在储存过程中,花生四烯酸含量的甘油磷脂,特别是磷脂酰乙醇胺和磷脂酰丝氨酸类中的含量相对增加,但所有样品类型中其他多不饱和脂肪酸含量的甘油磷脂的相对含量保持稳定。这些变化并没有直接转化为脂质介质(LM)谱,因为花生四烯酸衍生的促炎 LM 水平并没有特异性升高。相反,在 PlaC 和 EV 中检测到几种单羟基途径标志物和功能相关的 LM,包括促炎和抗炎 LM,并且在储存过程中,这两种 LM 的一些代表物质明显积累。通过 Western blot,显示这些途径的关键酶存在于血小板中,在许多情况下还存在于 EV 中。由于 EV 富含 LM 前体在其(磷脂)膜中,含有产生 LM 的酶,包含相关的单羟基途径标志物,并分泌最终的 LM 产物,因此 PlaC 衍生的 EV 可以参与炎症和愈合的调节,从而帮助血小板发挥其基本的生理功能。