Antimicrobial activity of PLUNC protects against Pseudomonas aeruginosa infection.
Antimicrobial activity of PLUNC protects against Pseudomonas aeruginosa infection.
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DOI：
10.4049/jimmunol.1001769
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
Di YP
中科院分区：
文献类型：
--
作者：
Lukinskiene L;Liu Y;Reynolds SD;Steele C;Stripp BR;Leikauf GD;Kolls JK;Di YP
上皮抗微生物活性可保护肺免受吸入病原体的侵害。杀菌/渗透性增加蛋白家族已在体外显示出抗微生物活性。PLC 1（腭、肺和鼻上皮癌相关）是一种25 kDa分泌蛋白，与杀菌/渗透性增加蛋白具有同源性，并在鼻咽和呼吸道上皮中表达。本研究的目的是确定是否可以限制铜绿假单胞菌感染的小鼠。产生转基因小鼠（Scgb 1a 1-hPLC 1），其中人PLC 1（hPLC 1）与Scgb 1a 1启动子定向至气道上皮。在整个气管和支气管气道的上皮细胞以及支气管肺泡灌洗液（BALF）中检测到人PLL 1蛋白（hPLL 1）。转基因小鼠BALF的体外抗菌活性高于野生型小鼠。在体内铜绿假单胞菌攻击后，Scgb 1a 1-hPLC 1转基因小鼠显示出增强的细菌清除。这伴随着中性粒细胞浸润和细胞因子水平的降低。更重要的是，在Scgb 1a 1-hPL转基因小鼠气道中过表达的hPL显著提高了小鼠抵抗铜绿假单胞菌诱导的呼吸道感染的存活率。这些数据表明，血小板是一种新的抗菌蛋白，可能在气道上皮介导的先天性免疫反应中起关键作用。
Epithelial antimicrobial activity may protect the lung against inhaled pathogens. The bactericidal/permeability-increasing protein family has demonstrated antimicrobial activity in vitro. PLUNC (palate, lung and nasal epithelium carcinoma associated) is a 25 kDa secreted protein that shares homology with bactericidal/permeability-increasing proteins and is expressed in nasopharyngeal and respiratory epithelium. The objective of this study was to determine whether PLUNC can limit Pseudomonas aeruginosa infection in mice. Transgenic mice (Scgb1a1-hPLUNC) were generated in which human PLUNC (hPLUNC) was directed to the airway epithelium with the Scgb1a1 promoter. The human PLUNC protein (hPLUNC) was detected in the epithelium throughout the trachea and bronchial airways and in bronchoalveolar lavage fluid (BALF). BALF from transgenic mice exhibited higher antibacterial activity than that from wild type littermates in vitro. Following in vivo P. aeruginosa challenge, Scgb1a1-hPLUNC transgenic mice displayed enhanced bacterial clearance. This was accompanied by a decrease in neutrophil infiltration and cytokine levels. More importantly, the over-expressed hPLUNC in Scgb1a1-hPLUNC transgenic mouse airway significantly enhanced mouse survival against P. aeruginosa induced respiratory infection. These data indicate that PLUNC is a novel antibacterial protein that likely plays a critical role in airway epithelium mediated innate immune response.
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影响因子：
3.1
作者：
HORWITZ, AH;WILLIAMS, RE;NOWAKOWSKI, G
通讯作者：
NOWAKOWSKI, G
影响因子：
4.4
作者：
LeClair, EE;Nomellini, V;Bingle, CD
通讯作者：
Bingle, CD
DOI：
10.1165/rcmb.2003-0142oc
发表时间：
2004-02-01
影响因子：
6.4
作者：
Campos, MA;Abreu, AR;Whitney, PL
通讯作者：
Whitney, PL
DOI：
10.1016/j.bbapap.2004.01.001
发表时间：
2004-06-01
影响因子：
3.2
作者：
Ghafouri, B;Kihlström, E;Lindahl, M
通讯作者：
Lindahl, M
影响因子：
4.4
作者：
Chu, Hong Wei;Thaikoottathil, Jyoti;Martin, Richard J.
通讯作者：
Martin, Richard J.