Effects of Staphylococcus aureus-hemolysin A on calcium signalling in immortalized human airway epithelial cells
Effects of Staphylococcus aureus-hemolysin A on calcium signalling in immortalized human airway epithelial cells
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DOI：
10.1016/j.ceca.2008.09.001
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发表时间：
2009-02-01
期刊：
影响因子：
4
通讯作者：
Hildebrandt, Jar-Peter
中科院分区：
文献类型：
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作者：
Eichstaedt, Stefanie;Gaebler, Karoline;Hildebrandt, Jar-Peter
支气管上皮对细菌定植的先天防御的一部分是盐和水的分泌，这通常依赖于受体介导的camp和钙信号的协调作用。金黄色葡萄球菌毒力因子干扰宿主细胞内源性信号的假设是通过测量激动剂介导的[Ca2+]变化，在S9细胞中与细菌分泌产物预先孵育。S9细胞对machr激活的反应是细胞内储存的钙释放和容性钙内流。用金黄色葡萄球菌（COL）培养上清液或重组α溶血素（Hla）处理细胞可导致[Ca2+]的时间和浓度依赖性变化(i)。高浓度的Hla （2000 ng/ml）导致钙内流加速引起的[Ca2+](i)升高。然而，没有发生一般hla介导的S9细胞膜对小分子的通透性。较低浓度的Hla （200 ng/ml）在受体介导的钙信号传导的持续平台期诱导[Ca2+](i)-水平的降低，这是通过用carboxyeosin（一种质膜钙- atp酶抑制剂）预先孵育细胞而消除的。这表明低浓度的Hla通过加速泵驱动的Ca2+离子挤压改变钙信号。在体内，这种机制可能导致钙介导的细胞防御功能的衰减和细菌粘附支气管上皮的促进。(C) 2008 Elsevier Ltd版权所有。
Part of the innate defence of bronchial epithelia against bacterial colonization is secretion of salt and water which generally depends on coordinated actions of receptor-mediated CAMP-and calcium signalling. The hypothesis that Staphylococcus aureus-virulence factors interfere with endogenous signals in host cells was tested by measuring agonist-mediated changes in [Ca2+], in S9 cells upon pre-incubation with bacterial secretory products. S9 cells responded to mAChR-activation with calcium release from intracellular stores and capacitative calcium influx. Treatment of cells with culture supernatants of S. aureus (COL) or with recombinant alpha-hemolysin (Hla) resulted in time- and concentration-dependent changes in [Ca2+](i). High concentrations of Hla (2000 ng/ml) resulted in elevations in [Ca2+](i) elicited by accelerated calcium influx. A general Hla-mediated permeabilization of S9 cell membranes to small molecules, however, did not occur. Lower concentrations of Hla (200 ng/ml) induced a reduction in [Ca2+](i)-levels during the sustained plateau phase of receptor-mediated calcium signalling which was abolished by pre-incubation of cells with carboxyeosin, an inhibitor of the plasma membrane calcium-ATPase. This indicates that low concentrations of Hla change calcium signalling by accelerating pump-driven extrusion of Ca2+ ions. In vivo, such a mechanism may result in attenuation of calcium-mediated cellular defence functions and facilitation of bacterial adherence to the bronchial epithelium. (C) 2008 Elsevier Ltd. All rights reserved.