Changes in astrocyte shape induced by sublytic concentrations of the cholesterol-dependent cytolysin pneumolysin still require pore-forming capacity.
Changes in astrocyte shape induced by sublytic concentrations of the cholesterol-dependent cytolysin pneumolysin still require pore-forming capacity.
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DOI：
10.3390/toxins3010043
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发表时间：
2011-01
期刊：
影响因子：
4.2
通讯作者：
Iliev AI
中科院分区：
文献类型：
--
作者：
Förtsch C;Hupp S;Ma J;Mitchell TJ;Maier E;Benz R;Iliev AI
肺炎链球菌是一种常见的病原体，可引起各种感染，如败血症和脑膜炎。肺炎链球菌的一个主要致病因素是胆固醇依赖的细胞溶血素，即肺炎溶血素。它在高浓度时产生细胞裂解，在较低浓度时产生凋亡。我们已经证明，亚溶血量的肺炎溶血素诱导人神经母细胞瘤细胞中依赖于GTP酶的肌动蛋白细胞骨架的小重组和微管的稳定，这表现为细胞回缩和细胞形状的改变。在这项研究中，我们利用实时成像方法来分析肺炎溶血素的成孔能力在原代星形胶质细胞肌动蛋白依赖的细胞形状变化中的作用。在最初用野生型毒素攻击后，在20-40分钟内迅速建立了通透性细胞群。在最初的快速通透化之后，通透性种群的规模保持不变，并达到了一个平台期。因此，我们分析了非通透性(非溶解)群体，这些群体表现出被肌动蛋白解聚抑制的回缩和形状变化。尽管肺炎溶血素治疗的性质不是溶解的，但毒素的溶解能力对于启动细胞形状改变仍然至关重要。非裂解性肺炎溶血素突变体W433F-肺炎溶血素和Delta6-肺炎溶血素以与野生型毒素相似的亲和力结合细胞膜，不能引起形状变化。野生型毒素引起的细胞形状改变和细胞收缩不依赖于钙、钠内流和膜去极化，这些都是在细胞受到攻击后发生的，推测是由于溶气素孔的离子通道性质造成的。排除了主要的与孔有关的现象，因为细胞形状变化的启动机制，提出了在肺炎溶血素的成孔能力和肌动蛋白细胞骨架重组之间存在更复杂的关系。
Streptococcus pneumoniae is a common pathogen that causes various infections, such as sepsis and meningitis. A major pathogenic factor of S. pneumoniae is the cholesterol-dependent cytolysin, pneumolysin. It produces cell lysis at high concentrations and apoptosis at lower concentrations. We have shown that sublytic amounts of pneumolysin induce small GTPase-dependent actin cytoskeleton reorganization and microtubule stabilization in human neuroblastoma cells that are manifested by cell retraction and changes in cell shape. In this study, we utilized a live imaging approach to analyze the role of pneumolysin’s pore-forming capacity in the actin-dependent cell shape changes in primary astrocytes. After the initial challenge with the wild-type toxin, a permeabilized cell population was rapidly established within 20-40 minutes. After the initial rapid permeabilization, the size of the permeabilized population remained unchanged and reached a plateau. Thus, we analyzed the non-permeabilized (non-lytic) population, which demonstrated retraction and shape changes that were inhibited by actin depolymerization. Despite the non-lytic nature of pneumolysin treatment, the toxin’s lytic capacity remained critical for the initiation of cell shape changes. The non-lytic pneumolysin mutants W433F-pneumolysin and delta6-pneumolysin, which bind the cell membrane with affinities similar to that of the wild-type toxin, were not able to induce shape changes. The initiation of cell shape changes and cell retraction by the wild-type toxin were independent of calcium and sodium influx and membrane depolarization, which are known to occur following cellular challenge and suggested to result from the ion channel-like properties of the pneumolysin pores. Excluding the major pore-related phenomena as the initiation mechanism of cell shape changes, the existence of a more complex relationship between the pore-forming capacity of pneumolysin and the actin cytoskeleton reorganization is suggested.
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DOI：
10.1152/ajplung.00134.2005
发表时间：
2005-10-01
影响因子：
4.9
作者：
Liu, CQ;Zuo, JM;Janssen, LJ
通讯作者：
Janssen, LJ
DOI：
10.1073/pnas.0608213104
发表时间：
2007-02-20
影响因子：
11.1
作者：
Iliev, Asparouh I.;Djannatian, Jasmin Roya;Wouters, Fred S.
通讯作者：
Wouters, Fred S.
影响因子：
5.5
作者：
Beurg, M;Hafidi, A;Dulon, D
通讯作者：
Dulon, D
影响因子：
2.9
作者：
KIMELBERG, HK;KETTENMANN, H
通讯作者：
KETTENMANN, H
DOI：
10.1016/j.bbrc.2008.01.151
发表时间：
2008-04-11
影响因子：
3.1
作者：
El-Rachkidy, Rana G.;Davies, Noel W.;Andrew, Peter W.
通讯作者：
Andrew, Peter W.