Department of Otolaryngology, Emory University, Atlanta, GA 30308, USA.
Int Forum Allergy Rhinol. 2013 Aug;3(8):630-5. doi: 10.1002/alr.21168. Epub 2013 Apr 16.
Epithelial permeability is highly dependent upon the integrity of tight junctions, which are cell-cell adhesion complexes located at the apical aspect of the lateral membrane of polarized epithelial cells. We hypothesize that sinonasal epithelial exposure to Der p 1 house dust mite antigen decreases expression of tight junction proteins (TJPs), representing a potential mechanism for increased permeability and presentation of antigens across the sinonasal epithelial layer.
Confluent cultured primary human sinonasal epithelial cells were exposed to recombinant Der p 1 antigen vs control, and transepithelial resistance measurements were performed over 24 hours. Antibody staining for a panel of TJPs was examined with immunofluorescence/confocal microscopy and Western blotting. Tissue for these experiments was obtained from 4 patients total.
Der p 1 exposed sinonasal cells showed a marked decrease in transepithelial resistance when compared to control cells. In addition, results of Western immunoblot and immunofluorescent labeling demonstrated decreased expression of TJPs claudin-1 and junction adhesion molecule-A (JAM-A) in Der p 1-exposed cultured sinonasal cells vs controls.
Der p 1 antigen exposure decreases sinonasal epithelium TJP expression, most notably seen in JAM-A and claudin-1 in these preliminary experiments. This decreased TJP expression likely contributes to increased epithelial permeability and represents a potential mechanism for transepithelial antigen exposure in allergic rhinitis.
上皮细胞通透性高度依赖于紧密连接的完整性,而紧密连接是位于极化上皮细胞侧膜顶侧的细胞-细胞粘附复合物。我们假设鼻黏膜上皮暴露于 Der p 1 屋尘螨抗原会降低紧密连接蛋白 (TJPs) 的表达,这代表了一种增加通透性和抗原呈递穿过鼻黏膜上皮层的潜在机制。
将培养的原代人鼻黏膜上皮细胞暴露于重组 Der p 1 抗原与对照,然后在 24 小时内进行跨上皮电阻测量。通过免疫荧光/共聚焦显微镜和 Western 印迹检查针对 TJPs 进行的抗体染色。这些实验的组织总共来自 4 位患者。
与对照细胞相比,暴露于 Der p 1 的鼻黏膜细胞的跨上皮电阻明显降低。此外,Western 免疫印迹和免疫荧光标记的结果表明,暴露于 Der p 1 的培养鼻黏膜细胞中 TJPs 紧密连接蛋白-1 (claudin-1) 和连接黏附分子-A (JAM-A) 的表达减少。
Der p 1 抗原暴露会降低鼻黏膜上皮 TJPs 的表达,在这些初步实验中,JAM-A 和 claudin-1 最为明显。这种 TJPs 表达的减少可能导致上皮通透性增加,并代表变应性鼻炎中跨上皮抗原暴露的潜在机制。