Unconventional apoptosis of polymorphonuclear neutrophils (PMN): staurosporine delays exposure of phosphatidylserine and prevents phagocytosis by MΦ‐2 macrophages of PMN
Unconventional apoptosis of polymorphonuclear neutrophils (PMN): staurosporine delays exposure of phosphatidylserine and prevents phagocytosis by MΦ‐2 macrophages of PMN
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多形核中性粒细胞 (PMN) 的非常规凋亡：星形孢菌素延迟磷脂酰丝氨酸的暴露并阻止 PMN Mδ2 巨噬细胞的吞噬作用
DOI：
10.1111/cei.12412
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发表时间：
2015
影响因子：
4.6
通讯作者：
Schiller M
中科院分区：
文献类型：
--
作者：
Franz S;Munoz LE;Heyder P;Herrmann M;Schiller M
多形核中性粒细胞（PMN）的凋亡和随后的“沉默”清除代表了炎症消退的重要检查点。PMN清除失败导致继发性坏死驱动的组织损伤与慢性炎症和自身免疫性疾病有关。凋亡的中性粒细胞经历了深刻的生物物理变化，保证他们的有效识别和吞噬细胞吸收之前褪色到继发性坏死。在这项研究中，我们证明，staurosporine（STS），一个非选择性的，但有效的抑制剂细胞周期蛋白依赖性激酶和蛋白激酶C，对中性粒细胞凋亡产生了巨大的影响。经STS处理的PMN经历了一种非常规形式的细胞死亡，其特征在于延迟暴露的氨基磷脂，包括磷脂酰丝氨酸（PS）和磷脂酰乙醇胺和增加暴露的新聚糖。STS导致受损的细胞碎片和加速DNA碎片。经STS处理的表面缺乏PS的PMN的吞噬作用显著降低，这突出了PS对于清除凋亡的PMN的重要性。免疫复合物的特异性调理作用完全恢复STS处理的PMN的吞噬作用，证明了在没有PS暴露的情况下备份清除途径的效率。
Apoptosis of polymorphonuclear neutrophils (PMN) and subsequent ‘silent’ removal represents an important check-point for the resolution of inflammation. Failure in PMN clearance resulting in secondary necrosis-driven tissue damage has been implicated in conditions of chronic inflammation and autoimmunity. Apoptotic PMN undergo profound biophysical changes that warrant their efficient recognition and uptake by phagocytes before fading to secondary necrosis. In this study, we demonstrate that staurosporine (STS), a non-selective but potent inhibitor of cyclin-dependent kinase and protein kinase C, exerts a drastic impact on PMN apoptosis. PMN treated with STS underwent an unconventional form of cell death characterized by a delayed exposure of aminophospholipids, including phosphatidylserine (PS) and phosphatidylethanolamine and an increased exposure of neo-glycans. STS caused an impaired cellular fragmentation and accelerated DNA fragmentation. Phagocytosis of STS-treated PMN lacking PS on their surfaces was decreased significantly, which highlights the importance of PS for the clearance of apoptotic PMN. Specific opsonization with immune complexes completely restored phagocytosis of STS-treated PMN, demonstrating the efficiency of back-up clearance pathways in the absence of PS exposure.
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影响因子：
7.2
作者：
Hochreiter-Hufford, Amelia;Ravichandran, Kodi S.
通讯作者：
Ravichandran, Kodi S.
中性粒细胞凋亡的温度依赖性抑制
影响因子：
4.8
作者：
J. Pryde;A. Walker;A. Rossi;S. Hannah;C. Haslett
通讯作者：
C. Haslett
中性粒细胞凋亡期间白唾液酸蛋白 (CD43) 下调、膜起泡和磷脂扰乱涉及不同的信号通路*
影响因子：
4.8
作者：
P. Nusbaum;C. Lainé;M. Bouaouina;S. Seveau;E. Cramer;J. Massé;P. Lesavre;L. Halbwachs‐Mecarelli
通讯作者：
L. Halbwachs‐Mecarelli
影响因子：
3.7
作者：
Orlando, KA;Stone, NL;Pittman, RN
通讯作者：
Pittman, RN
影响因子：
15.9
作者：
Huynh, MLN;Fadok, VA;Henson, PM
通讯作者：
Henson, PM