Autophagic vesicles on mature human reticulocytes explain phosphatidylserine-positive red cells in sickle cell disease
Autophagic vesicles on mature human reticulocytes explain phosphatidylserine-positive red cells in sickle cell disease
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DOI：
10.1182/blood-2015-04-637702
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发表时间：
2015-10-08
期刊：
影响因子：
20.3
通讯作者：
Anstee, David J.
中科院分区：
文献类型：
--
作者：
Mankelow, Tosti J.;Griffiths, Rebecca E.;Anstee, David J.
在成熟为红细胞的过程中，网织红细胞必须清除任何残留的细胞器，减少其表面积和体积。在这里，我们表明，这涉及到一个新的过程中，大，完整的，由内而外的磷脂酰丝氨酸（PS）暴露的自噬囊泡被挤出。细胞表面PS是启动吞噬作用的良好表征的凋亡信号。在脾切除术后或镰状细胞病（SCD）患者的外周血中，暴露于其表面PS的循环红细胞数量增加。我们发现，在这些患者中，PS是存在于红细胞的细胞表面上的大（类似于1.4 μ m）离散区域对应于自噬囊泡。在网织红细胞上发现的自噬囊泡与在脾切除个体和SCD患者的红细胞上观察到的自噬囊泡相同。我们的数据表明，与脾切除术相关的血栓形成风险增加，血红蛋白病患者的循环成熟网织红细胞表达由内而外PS暴露的自噬囊泡，因为无脾细胞水平增加的可能后果。
During maturation to an erythrocyte, a reticulocyte must eliminate any residual organelles andreduce itssurface area and volume. Here we show this involves a novel process where by large, intact, inside-out phosphatidylserine (PS)-exposed autophagic vesicles are extruded. Cell surface PS is a well-characterized apoptotic signal initiating phagocytosis. In peripheral blood from patients after splenectomy or in patients with sickle cell disease (SCD), the number of circulating red cells exposing PS on their surface is elevated. We show that in these patients PS is present on the cell surface of red cells in large (similar to 1.4 mu m) discrete areas corresponding to autophagic vesicles. The autophagic vesicles found on reticulocytes are identical to those observed on red cells from splenectomized individuals and patients with SCD. Our data suggest the increased thrombotic risk associated with splenectomy, and patients with hemoglobinopathies is a possible consequence of increased levels of circulating mature reticulocytes expressing inside-out PS-exposed autophagic vesicles because of asplenia.