Microparticle generation and leucocyte death in Shiga toxin-mediated HUS
Microparticle generation and leucocyte death in Shiga toxin-mediated HUS
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DOI：
10.1093/ndt/gfr748
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发表时间：
2012-07-01
影响因子：
6.1
通讯作者：
von Vietinghoff, Sibylle
中科院分区：
文献类型：
--
作者：
Ge, Shuwang;Hertel, Barbara;von Vietinghoff, Sibylle
滋贺毒素诱导的溶血性尿毒综合征（STEC-HUS）是一种以肾功能衰竭、神经功能障碍、溶血和血管内血栓形成为特征的急性多系统疾病。儿科患者中源自多种细胞类型（包括血小板和白细胞）的循环微粒升高。体外数据也表明滋贺毒素对白细胞死亡的修饰。在这里，我们研究了STEC-HUS成人患者在急性期和恢复期的微粒生成和体内白细胞死亡。多色流式细胞术和免疫荧光用于评估STEC-HUS成人患者在STEC-HUS期间在三级护理中心接受治疗的微粒浓度和血小板微粒接种到白细胞和白细胞死亡的来源。2011年德国暴发HUS，急性STEC-HUS时血小板和白细胞来源的血浆微粒浓度升高。在高比例的单核细胞和粒细胞上检测到血小板微粒（MP）。在治疗干预中，血浆置换降低了白细胞上的血小板标志物表达，补体抑制对循环MP的数量仅产生中度影响，并且未改变血小板微粒与白细胞的结合。与健康对照组相比，STEC-HUS患者中凋亡和坏死的单核细胞和粒细胞的数量显著增加。补体抑制显著增加循环凋亡细胞的数量。在随后分配到血浆置换或入住重症监护室的患者中，入院时单核细胞凋亡明显较高。在STEC-HUS中，检测到循环MP和死亡白细胞数量升高。单核细胞和粒细胞死亡是急性STEC-HUS的新标志物，其可通过释放促炎酶和细胞因子而积极促进组织破坏。
Shiga toxin-induced haemolytic uraemic syndrome (STEC-HUS) is an acute multisystem disorder characterized by renal failure, neurological dysfunction, haemolysis and intravascular thrombosis. Circulating microparticles originating from a number of cell types including thrombocytes and leucocytes are elevated in paediatric patients. In vitro data also suggest modification of leucocyte death by Shiga toxin. Here, we investigated microparticle generation and leucocyte cell death in vivo in adult STEC-HUS patients during acute disease and recovery.Multi-colour flow cytometry and immunofluorescence were used to assess microparticle concentration and provenience thrombocyte microparticle seeding to leucocytes and leucocyte cell death in adult STEC-HUS patients treated at a tertiary care centre during the STEC-HUS outbreak in Germany in 2011.Plasma microparticle concentrations of both platelet and leucocyte origin were elevated during acute STEC-HUS. Platelet microparticles (MP) were detected on a high proportion of monocytes and granulocytes. Among therapeutic interventions, plasma exchange reduced platelet marker expression on leucocytes, inhibition of complement had only moderate impact on the number of circulating MP and did not alter platelet microparticle binding to leucocytes. Numbers of apoptotic and necrotic monocytes and granulocytes were significantly increased in patients with STEC-HUS compared to healthy controls. Complement inhibition significantly increased the number of circulating apoptotic cells. Monocyte apoptosis on admission was significantly higher in patients subsequently assigned to plasma exchange or admitted to the intensive care unit.In STEC-HUS, elevated numbers of circulating MP and dead leucocytes were detected. Monocyte and granulocyte deaths are novel markers of acute STEC-HUS that may actively contribute to tissue destruction by liberation of pro-inflammatory enzymes and cytokines.