Cottrill Elizabeth E, Chen Bei, Adappa Nithin D, Palmer James N, Kennedy David W, Lee Robert J, Cohen Noam A
Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Philadelphia Veterans Administration Medical Center Surgical Services, Philadelphia, PA.
Int Forum Allergy Rhinol. 2017 Feb;7(2):154-159. doi: 10.1002/alr.21851. Epub 2016 Sep 21.
Antimicrobial peptides (AMPs) produced by the epithelium are important for innate immune defense. In 2001, a novel AMP dermcidin (DCD) was described with no homology to other AMPs and an expression pattern restricted to eccrine sweat glands. In contrast to other AMPs, DCD expression has not been shown to be induced under inflammatory conditions in the skin. After identifying DCD by mass spectrometry in a protein sample isolated from human nasal secretions, we sought to determine the role of DCD in innate defense of the sinonasal airway.
After institutional review board approval, sinonasal mucosal tissue specimens were acquired from residual clinical material obtained during sinonasal surgery and used to grow cultures in an air-liquid interface environment. After stimulation of the cultures with various bitter compounds and phosphate-buffered saline, airway surface liquid was collected, and a DCD-specific enzyme-linked immunoassay was used to quantify DCD in each sample. To localize DCD expression, ALI cultures were fixed and immunofluorescence performed against DCD, β-tubulin IV, and Muc-5A.
Enzyme-linked immunoassay showed DCD in air-surface liquid and in clinical nasal secretion samples at concentrations comparable to eccrine sweat. There was no evidence of inducible expression with any of the tested stimulants. Confocal microscopy revealed DCD expression in sinonasal mucosal goblet cells.
This is the first report of the presence of DCD in nasal mucosa and demonstration of DCD in clinical samples of human nasal secretions at clinically relevant concentrations, which may represent a novel arm of sinonasal airway innate defense.
上皮细胞产生的抗菌肽（AMPs）对先天性免疫防御很重要。2001年，一种新型抗菌肽——皮肤杀菌肽（DCD）被发现，它与其他抗菌肽无同源性，且表达模式局限于外分泌汗腺。与其他抗菌肽不同，尚未发现DCD的表达在皮肤炎症条件下会被诱导。在通过质谱法从人鼻分泌物中分离的蛋白质样品中鉴定出DCD后，我们试图确定DCD在鼻气道先天性防御中的作用。
经机构审查委员会批准后，从鼻手术期间获得的残余临床材料中获取鼻黏膜组织标本，并用于在气液界面环境中培养。在用各种苦味化合物和磷酸盐缓冲盐水刺激培养物后，收集气道表面液体，并使用DCD特异性酶联免疫测定法对每个样品中的DCD进行定量。为了定位DCD的表达，将气液界面培养物固定并用针对DCD、β-微管蛋白IV和粘蛋白5A进行免疫荧光检测。
酶联免疫测定显示气道表面液体和临床鼻分泌物样品中的DCD浓度与外分泌汗液相当。没有证据表明任何测试刺激物可诱导其表达。共聚焦显微镜显示鼻黏膜杯状细胞中有DCD表达。
这是关于鼻黏膜中存在DCD以及在人鼻分泌物临床样品中以临床相关浓度证明DCD存在的首次报告，这可能代表鼻气道先天性防御的一个新分支。
