Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Division of Rhinology, Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Int Forum Allergy Rhinol. 2021 May;11(5):877-884. doi: 10.1002/alr.22695. Epub 2020 Oct 11.
Solitary chemosensory cells (SCCs) in the murine nasal epithelium are discrete specialized cells that respond to irritants and activate trigeminal nerve fibers through the release of acetylcholine (ACh), resulting in local neurogenic inflammation. In addition to releasing ACh, SCCs are the exclusive epithelial source of interleukin (IL)-25. In humans, SCCs are significantly expanded in sinonasal polyps (NPs). However, the SCC-trigeminal synapse has yet to be demonstrated in human sinonasal epithelium.
Immunofluorescence for trigeminal nerve fiber markers, nicotinic ACh receptors (nChR), and SCC markers was performed in vibratome sections from polyp and healthy turbinate tissue. Quantitative polymerase chain reaction and immunofluorescence of cultured epithelial cells were used to evaluate the expansion of SCCs. Last, intracellular calcium imaging was used to demonstrate cholinergic signaling in sinonasal epithelial cells.
Calcitonin gene-related peptide (CGRP) immunostaining was used to identify cholinergic nerve endings, which were only evident in sections from the inferior turbinate and intertwined with SCCs (α-gustducin-positive cells). CGRP-positive nerve endings were not identified in sections from NPs. Human SCCs expressed nChR as well as the ACh synthetic enzyme choline acetyltransferase. Live cell calcium imaging demonstrated functionally active cholinergic signaling in discrete sinonasal epithelial cells, consistent with SCCs. Finally, SCC-specific genes were dramatically upregulated with pretreatment with IL-13 and nicotinic agonists.
SCCs are innervated by trigeminal nerve endings in healthy turbinate tissue but not in NPs. SCCs express ACh receptors as well as choline acetyltransferase and, in the setting of a type 2 inflammatory environment, denervated SCCs dramatically expand with nicotinic stimulation.
鼠类鼻上皮中的单个化学感觉细胞（SCCs）是离散的特化细胞，通过释放乙酰胆碱（ACh）来响应刺激物并激活三叉神经纤维，导致局部神经源性炎症。除了释放 ACh 之外，SCC 还是白细胞介素（IL）-25 的唯一上皮来源。在人类中，SCC 在鼻息肉（NP）中显著扩张。然而，SCC-三叉神经突触尚未在人类鼻上皮中得到证明。
在鼻息肉和健康鼻甲组织的振动切片上进行三叉神经纤维标志物、烟碱型乙酰胆碱受体（nChR）和 SCC 标志物的免疫荧光染色。使用定量聚合酶链反应和培养的上皮细胞免疫荧光评估 SCC 的扩张。最后，使用细胞内钙成像来证明鼻上皮细胞中的胆碱能信号。
降钙素基因相关肽（CGRP）免疫染色用于鉴定胆碱能神经末梢，仅在鼻甲的切片中可见，并且与 SCC（α- gustducin 阳性细胞）交织在一起。在 NP 的切片中未发现 CGRP 阳性神经末梢。人类 SCC 表达 nChR 以及 ACh 合成酶胆碱乙酰转移酶。活细胞钙成像显示离散的鼻上皮细胞中存在功能活跃的胆碱能信号，与 SCC 一致。最后，用 IL-13 和烟碱激动剂预处理后，SCC 特异性基因显著上调。
SCC 由健康鼻甲组织中的三叉神经末梢支配，但在 NP 中没有。SCC 表达 ACh 受体以及胆碱乙酰转移酶，并且在 2 型炎症环境中，去神经支配的 SCC 在烟碱刺激下会剧烈扩张。
