Rampey Andrew M, Lathers Deanne M R, Woodworth Bradford A, Schlosser Rodney J
Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina and the Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA.
Am J Rhinol. 2007 Jan-Feb;21(1):117-21. doi: 10.2500/ajr.2007.21.2998.
Dendritic cell (DC) activation and antigen presentation to T cells are critical to innate and adaptive immunity. Toll-like receptors (TLRs) are known to bind pathogen-associated molecular patterns in addition to sinonasally secreted surfactant proteins (SP) such as SP-A and SP-D. TLR binding is known to activate DCs. Based on these observations, we sought to establish the presence, in sinonasal mucosa, of DC and the pattern recognition receptors (PRRs), CD14, TLR2, and TLR4.
Sinonasal biopsy specimens were taken from patients with eosinophilic nonatopic nasal polyposis (n = 4), allergic fungal sinusitis (n = 1), and nondiseased patients undergoing cerebrospinal fluid leak repair or pituitary tumor resection (n = 2). Tissue samples were stained immunohistochemically for PRR (CD14, TLR2, and TLR4), mature DC marker (CD208), iDC marker (CD209), or isotype controls.
Immature and mature DC were immunolocalized to the subepithelial stroma and ciliated epithelial surface, respectively. Diffuse staining of CD14 was observed throughout the stroma with additional staining in the ciliated epithelium. The TLR markers showed no staining in the ciliated epithelium. TLR2 primarily localized in stroma immediately deep to the ciliated epithelial surface. TLR4 immunolocalized to submucosal seromucinous gland ductal epithelium. Data from nondiseased patients were mixed, with one patient showing minimal staining of any of the tested cellular markers.
This study indicates progressive DC activation and emigration of mature antigen-presenting cells from the epithelial surfaces of sinonasal mucosa. The presence of TLR known to bind SP-A and SP-D suggests a link between SP expression and immune response in sinonasal mucosa.
树突状细胞(DC)的激活以及向T细胞呈递抗原对于先天性和适应性免疫至关重要。已知Toll样受体(TLR)除了能结合鼻分泌物中的表面活性蛋白(SP),如SP-A和SP-D等病原体相关分子模式。已知TLR结合可激活DC。基于这些观察结果,我们试图确定鼻黏膜中DC以及模式识别受体(PRR)、CD14、TLR2和TLR4的存在情况。
从患有嗜酸性非特应性鼻息肉病的患者(n = 4)、变应性真菌性鼻窦炎患者(n = 1)以及接受脑脊液漏修补术或垂体肿瘤切除术的非患病患者(n = 2)获取鼻活检标本。对组织样本进行免疫组织化学染色,检测PRR(CD14、TLR2和TLR4)、成熟DC标志物(CD208)、未成熟DC标志物(CD209)或同型对照。
未成熟DC和成熟DC分别免疫定位于上皮下基质和纤毛上皮表面。在整个基质中观察到CD14的弥漫性染色,在纤毛上皮中也有额外染色。TLR标志物在纤毛上皮中无染色。TLR2主要定位于紧邻纤毛上皮表面深部的基质中。TLR4免疫定位于黏膜下浆液黏液性腺导管上皮。非患病患者的数据不一,有一名患者对任何测试的细胞标志物染色均极少。
本研究表明鼻黏膜上皮表面存在成熟抗原呈递细胞的渐进性DC激活和迁移。已知能结合SP-A和SP-D的TLR的存在提示了鼻黏膜中SP表达与免疫反应之间的联系。