The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface
The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface
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DOI：
10.1073/pnas.95.16.9541
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Wilson, JM
中科院分区：
文献类型：
--
作者：
Bals, R;Wang, XR;Wilson, JM
气道表面是宿主抵抗肺部感染的重要屏障。具有抗菌活性的蛋白质从上皮细胞分泌到气道表面上代表了这种先天免疫系统的重要组成部分。防御素是最具特征的上皮源性肽类抗生素。最近从人类骨髓中发现了另一个肽类抗生素家族的成员，称为cathelicidins。我们在这篇论文中表明，这种名为LL-37/hCAP-18的人肽也可能在人肺的先天免疫中发挥作用。原位杂交将高水平的LL-37/hCAP-18 RNA定位于传导气道的表面上皮细胞以及粘膜下腺体的浆液和粘液细胞。具有抗微生物活性的LL-37/hCAP-18肽部分地从来自人肺和人支气管异种移植模型的气道表面流体中纯化。合成肽LL-37表现出针对包括铜绿假单胞菌在内的许多革兰氏阴性和革兰氏阳性生物体的抗生素活性; LL-37的细菌杀伤对NaCl敏感并且与乳铁蛋白和溶菌酶协同。总之，我们表明LL-37/hCAP-18是一种具有广泛抗微生物活性的肽，其从人肺的上皮细胞分泌到气道表面上。
The airway surface is an important host defense against pulmonary infection. Secretion of proteins with antimicrobial activity from epithelial cells onto the airway surface represents an important component of this innate immune system. Defensins are the best characterized epithelial-derived peptide antibiotics. A member of another family of peptide antibiotics called cathelicidins recently was identified from human bone marrow. We show in this paper that this human peptide named LL-37/hCAP-18 also may play a role in innate immunity of the human lung. In situ hybridization localized high levels of LL-37/hCAP-18 RNA to surface epithelial cells of the conducting airway as well as serous and mucous cells of the submucosal glands. LL-37/hCAP-18 peptide with antimicrobial activity was partially purified from airway surface fluid from human lung and a human bronchial xenograft model, The synthetic peptide LL-37 demonstrated antibiotic activity against a number of Gram-negative and Gram-positive organisms including Pseudomonas aeruginosa; bacterial killing of LL-37 was sensitive to NaCl and was synergistic with lactoferrin and lysozyme. In summary, we show that LL-37/hCAP-18 is a peptide with broad antimicrobial activity that is secreted onto the airway surface from epithelial cells of the human lung.