毒蕈碱型乙酰胆碱受体激活在调节鼻黏膜免疫细胞活性中的作用。
Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosa.
机构信息
Department of Otolaryngology, Head & Neck Surgery, the First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
出版信息
Allergy. 2010 Aug;65(8):969-77. doi: 10.1111/j.1398-9995.2009.02281.x. Epub 2009 Nov 27.
BACKGROUND
The prevalence of airway inflammatory disorders keeps rising; its pathogenic mechanism is still not fully understood.
OBJECTIVE
The present study aimed to investigate the role of muscarinic receptor (M receptor) in regulating the immune cell activity in nasal mucosa by using surgical removed nasal mucosa from patients with nasal polyposis (NP) as a study platform.
METHODS
Human nasal mucosal sample was collected from inferior turbinectomy of 86 patients with NP or/and allergic rhinitis. Expression of tumor necrosis factor alpha (TNF-alpha), M receptor, OX40 ligand was measured in nasal mucosa by enzyme-linked immunosorbent assay, flow cytometry, and Western blotting assay.
RESULTS
When compared with non-NP (nNP) nasal mucosa, contents of TNF-alpha and TNF-alpha+ cells markedly increased in NP nasal mucosa; immune staining colocalized M3 receptor+ and TNF-alpha+ cells in NP nasal mucosa; exposure of isolated CD4+ T cells to methacholine induced the release of TNF-alpha. We also found CD11c+/M3 receptor+ cells in NP nasal mucosa. Methacholine increased the expression of OX40L in dendritic cells. Staphylococcal (S) aureus and S. enterotoxin B (SEB) were detected in NP nasal mucosa. Exposure of dendritic cells or naïve CD4+ T cells to SEB initiated the expression of M3 receptor at mRNA and protein levels.
CONCLUSIONS
The present data demonstrate that parasympathetic activity has the capacity to activate dendritic cells to release OX40 ligand, the latter induces CD4+ T cells to produce IL-4 and TNF-alpha that may further contribute to the pathogenesis of NP.
背景
气道炎症性疾病的患病率不断上升，但其发病机制尚不完全清楚。
目的
本研究旨在通过使用手术切除鼻息肉（NP）患者的鼻黏膜作为研究平台，探讨毒蕈碱受体（M 受体）在调节鼻黏膜免疫细胞活性中的作用。
方法
从 86 例 NP 或/和变应性鼻炎患者的下鼻甲切除术采集人鼻黏膜标本。通过酶联免疫吸附试验、流式细胞术和 Western blot 检测鼻黏膜中肿瘤坏死因子-α（TNF-α）、M 受体、OX40 配体的表达。
结果
与非 NP（nNP）鼻黏膜相比，NP 鼻黏膜中 TNF-α和 TNF-α+细胞含量明显增加；免疫染色显示 NP 鼻黏膜中 M3 受体+和 TNF-α+细胞共定位；分离的 CD4+T 细胞暴露于乙酰甲胆碱可诱导 TNF-α释放。我们还发现 NP 鼻黏膜中有 CD11c+/M3 受体+细胞。乙酰甲胆碱增加树突状细胞中 OX40L 的表达。NP 鼻黏膜中检测到金黄色葡萄球菌（S）和肠毒素 B（SEB）。SEB 暴露于树突状细胞或幼稚 CD4+T 细胞可引发 M3 受体在 mRNA 和蛋白水平上的表达。
结论
本研究数据表明，副交感神经活动具有激活树突状细胞释放 OX40 配体的能力，后者诱导 CD4+T 细胞产生 IL-4 和 TNF-α，这可能进一步导致 NP 的发病机制。
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