Suicidal erythrocyte death in sepsis
Suicidal erythrocyte death in sepsis
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DOI：
10.1007/s00109-006-0123-8
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发表时间：
2007-03-01
影响因子：
4.7
通讯作者：
Lang, Florian
中科院分区：
文献类型：
--
作者：
Kempe, Daniela S.;Akel, Ahmad;Lang, Florian
败血症的后遗症包括贫血，这可能是由于循环血液中红细胞的加速清除所致。然而，根本的机制迄今仍然难以捉摸。最近的研究表明，增加的胞质Ca 2+活性和神经酰胺都能引发自杀性红细胞死亡（即，红细胞凋亡），其特征在于细胞膜的脂质紊乱，导致磷脂酰丝氨酸暴露在红细胞表面。暴露磷脂酰丝氨酸的红细胞可粘附于血管壁或可被配备有磷脂酰丝氨酸受体的巨噬细胞吞噬。为了探索脓毒症是否导致红细胞增多，将来自健康志愿者的红细胞暴露于患有脓毒症的患者的血浆或暴露于来自产生脓毒症的病原体的上清液。然后，通过流式细胞术测定磷脂酰丝氨酸暴露（膜联蛋白V结合）、细胞体积（前向散射）、细胞溶质Ca2+活性（Fluo3荧光）和神经酰胺形成（抗神经酰胺抗体）。用来自患者的血浆而不是来自健康个体的血浆激发红细胞触发膜联蛋白V结合。患者血浆对红细胞膜联蛋白V结合的影响与神经酰胺的形成和胞浆Ca 2+活性的显着增加平行。红细胞暴露于病原体的上清液同样诱导红细胞凋亡，与鞘磷脂酶活性相关的影响。本研究揭示了脓毒症患者贫血和微循环紊乱的一种新的病理生理机制。暴露于脓毒症患者的血浆会触发磷脂酰丝氨酸暴露，导致粘附于血管壁并从循环血液中清除。
Sequelae of sepsis include anemia which presumably results from accelerated clearance of erythrocytes from circulating blood. The underlying mechanisms, however, remained hitherto elusive. Most recent studies disclosed that increased cytosolic Ca2+ activity and ceramide both trigger suicidal erythrocyte death (i.e., eryptosis), which is characterized by lipid scrambling of the cell membrane leading to phosphatidylserine exposure at the erythrocyte surface. Phosphatidylserine exposing erythrocytes may adhere to vascular walls or may be engulfed by macrophages equipped with phosphatidylserine receptors. To explore whether sepsis leads to eryptosis, erythrocytes from healthy volunteers were exposed to plasma of patients suffering from sepsis, or to supernatants from sepsis producing pathogens. Then, phosphatidylserine exposure (annexin V binding), cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3 fluorescence), and ceramide formation (anti-ceramide antibody) were determined by flow cytometry. Challenge of erythrocytes with plasma from the patients but not with plasma from healthy individuals triggered annexin V binding. The effect of patient plasma on erythrocyte annexin V binding was paralleled by formation of ceramide and a significant increase of cytosolic Ca2+ activity. Exposure of erythrocytes to supernatant of pathogens similarly induced eryptosis, an effect correlating with sphingomyelinase activity. The present observations disclose a novel pathophysiological mechanism leading to anemia and derangement of microcirculation during sepsis. Exposure to plasma from septic patients triggers phosphatidylserine exposure leading to adherence to the vascular wall and clearance from circulating blood.