血激肽素-1 可刺激巨噬细胞产生 C-C 基序趋化因子配体 24，从而增强鼻息肉中的嗜酸性粒细胞炎症。
Hemokinin-1 stimulates C-C motif chemokine ligand 24 production in macrophages to enhance eosinophilic inflammation in nasal polyps.
机构信息
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
出版信息
Int Forum Allergy Rhinol. 2019 Nov;9(11):1334-1345. doi: 10.1002/alr.22430. Epub 2019 Sep 23.
BACKGROUND
The mechanisms underlying mucosal eosinophilia in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly clarified. The nervous system and neuropeptides play an important role in the regulation of immune response. Herein we explore the expression and function of hemokinin-1 (HK-1), a newly identified tachykinin, along with its receptor neurokinin 1 receptor (NK1R) in CRSwNP.
METHODS
HK-1, NK1R, and C-C motif chemokine ligand 24 (CCL24) expression in nasal tissues (53 eosinophilic CRSwNP, 32 non-eosinophilic CRSwNP, and 33 controls) was investigated by quantitative reverse transcript polymerase chain reaction (RT-PCR) and immunofluorescence staining. THP-1, a human monocytic leukemia cell line, and eosinophilic polyp tissues were stimulated with HK-1. Cells, tissues, and culture supernatants were subsequently collected for detection of the production of various inflammatory cytokines and chemokines by quantitative RT-PCR and enzyme-linked immunoassay.
RESULTS
HK-1 and NK1R mRNA and protein expression were upregulated in eosinophilic and non-eosinophilic nasal polyps compared with control tissues, with eosinophilic polyps demonstrating a higher upregulation compared with that of non-eosinophilic polyps. Eosinophils constituted the major source of HK-1, whereas macrophages were the predominant cell type exhibiting NK1R in eosinophilic polyps. HK-1 induced CCL24 production from macrophages differentiated from THP-1 cells; this was abolished by an NK1R antagonist. HK-1 also induced CCL24 production from ex vivo-cultured eosinophilic nasal polyps. CCL24 was expressed by macrophages in eosinophilic but not non-eosinophilic polyps. The expression level of HK-1 correlated with CCL24 expression and tissue eosinophilia in eosinophilic nasal polyps.
CONCLUSION
Eosinophil-derived HK-1 induces CCL24 production from macrophages and therefore exaggerates eosinophilic inflammation in CRSwNP.
背景
慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）黏膜嗜酸性粒细胞增多的机制仍不清楚。神经系统和神经肽在调节免疫反应中发挥重要作用。在此，我们研究了一种新发现的速激肽——血啡肽-1（HK-1）及其受体神经激肽 1 受体（NK1R）在 CRSwNP 中的表达和功能。
方法
通过定量逆转录聚合酶链反应（RT-PCR）和免疫荧光染色，检测鼻组织（53 例嗜酸性粒细胞性 CRSwNP、32 例非嗜酸性粒细胞性 CRSwNP 和 33 例对照）中 HK-1、NK1R 和 C-C 基序趋化因子配体 24（CCL24）的表达。用 HK-1 刺激 THP-1 人单核白血病细胞系和嗜酸性息肉组织。随后收集细胞、组织和培养上清液，通过定量 RT-PCR 和酶联免疫吸附试验检测各种炎症细胞因子和趋化因子的产生。
结果
与对照组织相比，HK-1 和 NK1R 的 mRNA 和蛋白表达在嗜酸性和非嗜酸性鼻息肉中均上调，且嗜酸性息肉的上调程度高于非嗜酸性息肉。嗜酸性粒细胞是 HK-1 的主要来源，而巨噬细胞是嗜酸性息肉中 NK1R 的主要表达细胞类型。HK-1 诱导 THP-1 细胞分化的巨噬细胞产生 CCL24；这一过程被 NK1R 拮抗剂所阻断。HK-1 还诱导体外培养的嗜酸性鼻息肉产生 CCL24。CCL24 仅在嗜酸性息肉的巨噬细胞中表达，而非嗜酸性息肉中不表达。HK-1 的表达水平与嗜酸性鼻息肉中 CCL24 的表达和组织嗜酸性粒细胞增多相关。
结论
嗜酸性粒细胞衍生的 HK-1 诱导巨噬细胞产生 CCL24，从而加重 CRSwNP 中的嗜酸性粒细胞炎症。
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