Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, University Medical Center Groningen, Hanzeplein 1, NL-9713GZ Groningen, The Netherlands.
Thorax. 2012 Jun;67(6):488-95. doi: 10.1136/thoraxjnl-2011-200606. Epub 2011 Dec 13.
House dust mite (HDM) allergens have been reported to increase airway epithelial permeability, thereby facilitating access of allergens and allergic sensitisation.
The authors aimed to understand which biochemical properties of HDM are critical for epithelial immune and barrier responses as well as T helper 2-driven experimental asthma in vivo.
Three commercially available HDM extracts were analysed for endotoxin levels, protease and chitinase activities and effects on transepithelial resistance, junctional proteins and pro-inflammatory cytokine release in the bronchial epithelial cell line 16HBE and normal human bronchial cells. Furthermore, the effects on epithelial remodelling and airway inflammation were investigated in a mouse model.
The different HDM extracts varied extensively in their biochemical properties and induced divergent responses in vitro and in vivo. Importantly, the Greer extract, with the lowest serine protease activity, induced the most pronounced effects on epithelial barrier function and CCL20 release in vitro. In vivo, this extract induced the most profound epithelial E-cadherin delocalisation and increase in CCL20, CCL17 and interleukin 5 levels, accompanied by the most pronounced induction of HDM-specific IgE, goblet cell hyperplasia, eosinophilic inflammation and airway hyper-reactivity.
This study shows the ability of HDM extracts to alter epithelial immune and barrier responses is related to allergic sensitisation but independent of serine/cysteine protease activity.
屋尘螨（HDM）过敏原已被报道可增加气道上皮通透性，从而使过敏原和过敏致敏更容易进入。
作者旨在了解 HDM 的哪些生化特性对于上皮免疫和屏障反应以及体内 T 辅助 2 驱动的实验性哮喘至关重要。
分析了三种市售的 HDM 提取物的内毒素水平、蛋白酶和几丁质酶活性以及对支气管上皮细胞系 16HBE 和正常人支气管细胞的跨上皮电阻、连接蛋白和促炎细胞因子释放的影响。此外，还在小鼠模型中研究了它们对上皮重塑和气道炎症的影响。
不同的 HDM 提取物在生化特性上差异很大，在体外和体内引起了不同的反应。重要的是，具有最低丝氨酸蛋白酶活性的 Greer 提取物在体外诱导上皮屏障功能和 CCL20 释放方面的作用最为显著。在体内，这种提取物诱导上皮 E-钙黏蛋白最明显的去定位和 CCL20、CCL17 和白细胞介素 5 水平的增加，同时伴随着最显著的 HDM 特异性 IgE、杯状细胞增生、嗜酸性粒细胞炎症和气道高反应性的诱导。
这项研究表明，HDM 提取物改变上皮免疫和屏障反应的能力与过敏致敏有关，但与丝氨酸/半胱氨酸蛋白酶活性无关。
