Modulation of cytosolic Ca(2+) concentration in airway epithelial cells by Pseudomonas aeruginosa.

Modulation of cytosolic Ca(2+) concentration in airway epithelial cells by Pseudomonas aeruginosa.
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铜绿假单胞菌对气道上皮细胞胞浆 Ca(2) 浓度的调节。

DOI:
10.1128/iai.70.11.6399-6408.2002
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发表时间:
2002
影响因子:
3.1
通讯作者:
Machen,TerryE
Machen,TerryE
中科院分区:
医学2区
文献类型:
--
作者:
Jacob,Tobias;Lee,RebeccaJ;Engel,JoanneN;Machen,TerryE

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调节胞浆内Ca 2+浓度(Cai)可能是气道上皮细胞暴露于铜绿假单胞菌时重要的宿主反应。我们测量了Caiin Calu-3细胞从顶侧或基底侧表面暴露于细胞毒性和非细胞毒性菌株的P。铜绿。在3小时的时间内,顶端添加非细胞毒性菌株或细胞毒性菌株均未影响Cai,在基底外侧添加非细胞毒性菌株后也未观察到变化。相比之下,基底外侧添加细胞毒性菌株导致Cai从100 nM缓慢增加到200至400 nM。这种增加开始后20至50分钟,并持续了额外的30至75分钟,在这个时候,细胞变得nonviable.P. aerobosa-induced Cai的增加被阻断的Ca通道阻滞剂La 3+的基底侧,但不顶室。同样,用无钙溶液替换基底外侧培养基而不是顶侧培养基可以预防P。aerodynosa-mediated的变化在蔡。与PA 103的同基因突变体,我们证明了III型分泌装置,III型分泌的效应ExoU,和IV型皮利是必要的增加蔡。我们认为ExoU通过极化的气道上皮细胞的基底外侧表面通过III型分泌器的易位导致储存在内质网中的Ca的释放和上皮细胞基底外侧膜中的Ca通道的激活。
Modulation of cytosolic (intracellular) Ca2+concentration (Cai) may be an important host response when airway epithelial cells are exposed toPseudomonas aeruginosa. We measured Caiin Calu-3 cells exposed from the apical or basolateral surface to cytotoxic and noncytotoxic strains ofP. aeruginosa. Apical addition of either noncytotoxic strains or cytotoxic strains failed to affect Caiover a 3-h time period, nor were changes observed after basolateral addition of noncytotoxic strains. In contrast, basolateral addition of cytotoxic strains caused a slow increase in Caifrom 100 nM to 200 to 400 nM. This increase began after 20 to 50 min and persisted for an additional 30 to 75 min, at which time the cells became nonviable.P. aeruginosa-induced increases in Caiwere blocked by the addition of the Ca channel blocker La3+to the basolateral but not to the apical chamber. Likewise, replacing the basolateral but not the apical medium with Ca-free solution preventedP. aeruginosa-mediated changes in Cai. With isogenic mutants of PA103, we demonstrated that the type III secretion apparatus, the type III-secreted effector ExoU, and type IV pili were necessary for increased Cai. We propose that translocation of ExoU through the basolateral surface of polarized airway epithelial cells via the type III secretion apparatus leads to release of Ca stored in the endoplasmic reticulum and activation of Ca channels in the basolateral membranes of epithelial cells.
DOI: 10.1073/pnas.95.23.13899
发表时间: 1998-11-10
影响因子: 11.1
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