The Pseudomonas toxin pyocyanin inhibits the dual oxidase-based antimicrobial system as it imposes oxidative stress on airway epithelial cells.
The Pseudomonas toxin pyocyanin inhibits the dual oxidase-based antimicrobial system as it imposes oxidative stress on airway epithelial cells.
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DOI：
10.4049/jimmunol.181.7.4883
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发表时间：
2008-10-01
期刊：
影响因子：
--
通讯作者：
Leto TL
中科院分区：
文献类型：
--
作者：
Rada B;Lekstrom K;Damian S;Dupuy C;Leto TL
双氧化酶-硫氰酸盐-乳酸过氧化物酶（Duox/SCN−/LPO）系统利用从气道上皮顶端表面释放的LPO、硫氰酸盐和Duox衍生的过氧化氢，在气道表面液体中产生杀微生物氧化剂次硫氰酸盐。该系统对感染囊性纤维化和其他免疫功能低下患者气道的几种微生物有效。我们在这里表明，长期培养获得的铜绿假单胞菌暴露于气道上皮细胞可抑制duox1依赖性过氧化氢释放，表明某些微生物因子抑制Duox活性。这些抑制作用在缺乏花青素的铜绿假单胞菌PA14 Phz1/2中没有发现。我们发现纯化的pyocyanin，一种由P. aeruginosa产生的氧化还原活性毒力因子，通过消耗细胞内NADPH的储存来抑制人气道细胞Duox活性，因为它产生细胞内超氧化物。长期暴露于pyocyanin的人气道（原代正常人支气管和NCI-H292）细胞也会阻断Th2细胞因子（IL-4, IL-13）对Duox1的诱导，而抗氧化剂谷胱甘肽和n -乙酰半胱氨酸可以阻止这种诱导。此外，我们发现低浓度的pyocyanin阻断了Duox/SCN-/LPO系统对野生型铜绿假单胞菌原代正常人支气管上皮细胞的杀伤作用。因此，pyocyanin可以破坏假单胞菌被基于duo的系统杀死，因为它对宿主施加氧化应激。我们还表明，乳过氧化物酶可以氧化花青素，从而降低其细胞毒性。这些数据表明，通过病原体和宿主之间的竞争性氧化还原反应，pyocyanin在铜绿假单胞菌在人气道中的生存中发挥了新的作用。
The dual oxidase-thiocyanate-lactoperoxidase (Duox/SCN−/LPO) system generates the microbicidal oxidant hypothiocyanite in the airway surface liquid by using LPO, thiocyanate, and Duox-derived hydrogen peroxide released from the apical surface of the airway epithelium. This system is effective against several microorganisms that infect airways of cystic fibrosis and other immunocompromised patients. We show here that exposure of airway epithelial cells to Pseudomonas aeruginosa obtained from long-term cultures inhibits Duox1-dependent hydrogen peroxide release, suggesting some microbial factor suppresses Duox activity. These inhibitory effects were not seen with the pyocyanin-deficient P. aeruginosa strain, PA14 Phz1/2. We showed that purified pyocyanin, a redox-active virulence factor produced by P. aeruginosa, inhibits human airway cell Duox activity by depleting intracellular stores of NADPH, as it generates intracellular superoxide. Long-term exposure of human airway (primary normal human bronchial and NCI-H292) cells to pyocyanin also blocks induction of Duox1 by Th2 cytokines (IL-4, IL-13), which was prevented by the anti-oxidants glutathione and N-acetylcysteine. Furthermore, we showed that low concentrations of pyocyanin blocked killing of wild-type P. aeruginosa by the Duox/SCN-/LPO system on primary normal human bronchial epithelial cells. Thus, pyocyanin can subvert Pseudomonas killing by the Duox-based system as it imposes oxidative stress on the host. We also show that lactoperoxidase can oxidize pyocyanin, thereby diminishing its cytotoxicity. These data establish a novel role for pyocyanin in the survival of Pseudomonas aeruginosa in human airways through competitive redox-based reactions between the pathogen and host.
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影响因子：
--
作者：
LENANDERLUMIKARI, M
通讯作者：
LENANDERLUMIKARI, M
DOI：
10.1165/ajrcmb.22.6.3980
发表时间：
2000-06-01
影响因子：
6.4
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1164/ajrccm.164.6.2012139
发表时间：
2001-09-15
影响因子：
24.7
作者：
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通讯作者：
Chapman, KR