The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection
The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection
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DOI：
10.1038/nm1407
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发表时间：
2006-06-01
期刊：
影响因子：
82.9
通讯作者：
Brauner, Annelie
中科院分区：
文献类型：
--
作者：
Chromek, Milan;Slamova, Zuzana;Brauner, Annelie
泌尿系统紧邻外界环境发挥作用，但必须保持无微生物定植以避免疾病。在该区域建立抗菌屏障的机制尚未完全清楚。在此，我们分别描述了人源和鼠源泌尿系统上皮细胞中抗菌肽LL - 37及其前体hCAP - 18和其同源物CRAMP的产生及功能。细菌与上皮细胞接触导致相应肽段的快速产生和分泌，并且在人类中LL - 37/hCAP - 18被释放到尿液中。上皮细胞衍生的抗菌肽对泌尿系统免受感染起到重要作用，这通过使用CRAMP缺陷型和中性粒细胞耗竭型小鼠得以证明。此外，对LL - 37更具抗性的临床大肠杆菌菌株比敏感菌株引起更严重的泌尿系统感染。因此，抗菌肽似乎是泌尿系统黏膜免疫的关键因素。
The urinary tract functions in close proximity to the outside environment, yet must remain free of microbial colonization to avoid disease. The mechanisms for establishing an antimicrobial barrier in this area are not completely understood. Here, we describe the production and function of the cathelicidin antimicrobial peptides LL-37, its precursor hCAP-18 and its ortholog CRAMP in epithelial cells of human and mouse urinary tract, respectively. Bacterial contact with epithelial cells resulted in rapid production and secretion of the respective peptides, and in humans LL-37/hCAP-18 was released into urine. Epithelium-derived cathelicidin substantially contributed to the protection of the urinary tract against infection, as shown using CRAMP-deficient and neutrophil-depleted mice. In addition, clinical E. coli strains that were more resistant to LL-37 caused more severe urinary tract infections than did susceptible strains. Thus, cathelicidin seems to be a key factor in mucosal immunity of the urinary tract.