Pseudomonas aeruginosa vesicles associate with and are internalized by human lung epithelial cells.
Pseudomonas aeruginosa vesicles associate with and are internalized by human lung epithelial cells.
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DOI：
10.1186/1471-2180-9-26
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发表时间：
2009-02-03
期刊：
影响因子：
4.2
通讯作者：
Kuehn MJ
中科院分区：
文献类型：
--
作者：
Bauman SJ;Kuehn MJ
铜绿假单胞菌是囊性纤维化（CF）患者慢性和最终致死性肺部感染的主要病原体。为了研究铜绿假单胞菌衍生的囊泡如何导致肺部疾病，我们探索了它们与人类肺细胞相关的能力。纯化的囊泡与肺细胞相关，并以时间和剂量依赖性方式内化。来自CF分离株的囊泡与肺细胞的相关性是来自实验室菌株PAO 1的囊泡的3- 4倍。囊泡内化是温度依赖性的，并抑制高渗蔗糖和环糊精。表面结合囊泡很少与网格蛋白共定位。内化的囊泡与内质网（ER）标记物TRAPα以及霍乱毒素和转铁蛋白的ER定位池共定位。铜绿假单胞菌的CF分离物大量分泌PaAP（PA 2939），其是一种与囊泡表面缔合的氨肽酶。来自PaAP敲除菌株的囊泡表现出细胞缔合减少40%。同样，来自PAO 1过表达PaAP的囊泡显示细胞缔合显著增加。这些数据表明，PaAP促进囊泡与肺细胞的关联。总之，这些结果表明，铜绿假单胞菌囊泡可以与肺上皮细胞相互作用并被其内化，并有助于感染期间的炎症反应。
Pseudomonas aeruginosa is the major pathogen associated with chronic and ultimately fatal lung infections in patients with cystic fibrosis (CF). To investigate how P. aeruginosa-derived vesicles may contribute to lung disease, we explored their ability to associate with human lung cells. Purified vesicles associated with lung cells and were internalized in a time- and dose-dependent manner. Vesicles from a CF isolate exhibited a 3- to 4-fold greater association with lung cells than vesicles from the lab strain PAO1. Vesicle internalization was temperature-dependent and was inhibited by hypertonic sucrose and cyclodextrins. Surface-bound vesicles rarely colocalized with clathrin. Internalized vesicles colocalized with the endoplasmic reticulum (ER) marker, TRAPα, as well as with ER-localized pools of cholera toxin and transferrin. CF isolates of P. aeruginosa abundantly secrete PaAP (PA2939), an aminopeptidase that associates with the surface of vesicles. Vesicles from a PaAP knockout strain exhibited a 40% decrease in cell association. Likewise, vesicles from PAO1 overexpressing PaAP displayed a significant increase in cell association. These data reveal that PaAP promotes the association of vesicles with lung cells. Taken together, these results suggest that P. aeruginosa vesicles can interact with and be internalized by lung epithelial cells and contribute to the inflammatory response during infection.
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影响因子：
4.9
作者：
Kadurugamuwa, JL;Beveridge, TJ
通讯作者：
Beveridge, TJ
影响因子：
2.1
作者：
Keenan, J;Day, T;Bagshaw, P
通讯作者：
Bagshaw, P
DOI：
10.1152/ajplung.00322.2004
发表时间：
2005-02-01
影响因子：
4.9
作者：
Malloy, JL;Veldhuizen, RAW;Wright, JR
通讯作者：
Wright, JR
影响因子：
3.2
作者：
HANCOCK, REW;NIKAIDO, H
通讯作者：
NIKAIDO, H
影响因子：
2.8
作者：
Nouwens, AS;Beatson, SA;Cordwell, SJ
通讯作者：
Cordwell, SJ