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浙江大学学报（医学版）
浙江大学学报（医学版）  2021, Vol. 50 Issue (1): 123-130    DOI: 10.3724/zdxbyxb-2021-0030
综述     
中性粒细胞在哮喘中的地位和作用
陈菲(),虞敏,钟永红,华雯,黄华琼()
浙江大学医学院附属第二医院呼吸与危重症医学科，浙江 杭州310009
The role of neutrophils in asthma
CHEN Fei(),YU Min,ZHONG Yonghong,HUA Wen,HUANG Huaqiong()
Department of Respiratory and Critical Care Medicine，the Second Affiliated Hospital，Zhejiang University School of Medicine，Hangzhou 310009，China
 全文: PDF(2608 KB)   HTML( 14 )
摘要：

支气管哮喘是由多种细胞包括气道的炎性细胞和结构细胞及细胞组分参与的气道慢性炎症性疾病，其特征为气道炎症、气道高反应性、可逆性气道阻塞和气道重塑。以往哮喘被认为主要由2型炎症因子驱动，Th2细胞分泌IL-4、IL-5和IL-13，引起气道嗜酸性粒细胞炎症。随着研究的深入，发现中性粒细胞与哮喘炎症过程也存在密切关系。哮喘患者气道中的中性粒细胞在趋化增加的同时凋亡下降，从而导致中性粒细胞数量增多。中性粒细胞比嗜酸性粒细胞更早到达，通过产生弹性蛋白酶、髓过氧化物酶、中性粒细胞胞外诱捕网、趋化因子和细胞因子等，参与哮喘的发生及发展过程。针对这些效应分子的拮抗剂如抗IL-8受体抗体、抗IL-17抗体，DNA酶显示出对中性粒细胞哮喘的治疗作用，但应用于临床还需要更多的实验数据支持。本文主要就中性粒细胞在哮喘中的地位和作用作一综述。
关键词： 中性粒细胞;  哮喘;  中性粒细胞哮喘;  治疗; 综述    
Abstract:

Bronchial asthma is a chronic respiratory disease，characterized by airway inflammation，airway hyperresponsiveness，reversible airway obstruction and airway remodeling，in which a variety of cells including airway inflammatory cells and structural cells are involved. Previous studies have shown that asthma is mainly driven by Th2 cytokines IL-4，IL-5，and IL-13，leading to airway eosinophil inflammation. With further research，however，it has been found that neutrophils are also closely related to asthma. Numbers of neutrophils are elevated in airway through increased chemotaxis and decreased apoptosis，which is earlier than eosinophils，leading to airway neutrophilic inflammation. Neutrophils can produce elastase，myeloperoxidase，neutrophil extra- cellular traps，chemokines and cytokines，participating in the occurrence and development of asthma. The antagonists against these molecules，such as anti-IL-8 receptor antibody，anti-IL-17 antibody，and DNase，have shown positive effects on neutrophilic asthma，but further studies are needed to support their clinical application. This article mainly reviews the role of neutrophils in asthma and related mechanisms.
Key words: Neutrophils    Asthma    Neutrophilic asthma    Therapy； Review
收稿日期: 2020-09-14 出版日期: 2021-05-14
CLC:  R562.1  
基金资助: 国家重点研发计划（2017YFC131060）; 浙江省自然科学基金（LQ18H010002）
通讯作者: 黄华琼     E-mail: chenfei66@zju.edu.cn;zr_hhq@zju.edu.cn
作者简介: 陈菲，硕士研究生，主要从事呼吸系统慢性疾病研究; E-mail:chenfei66@zju.edu.cn; https://orcid.org/0000-0001-6017-2785
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引用本文:

陈菲,虞敏,钟永红,华雯,黄华琼. 中性粒细胞在哮喘中的地位和作用[J]. 浙江大学学报（医学版）, 2021, 50(1): 123-130.

CHEN Fei,YU Min,ZHONG Yonghong,HUA Wen,HUANG Huaqiong. The role of neutrophils in asthma. J Zhejiang Univ (Med Sci), 2021, 50(1): 123-130.

链接本文:

http://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0030    或    http://www.zjujournals.com/med/CN/Y2021/V50/I1/123

图 1  中性粒细胞在哮喘中的作用机制示意图 香烟烟雾、颗粒物、微生物等刺激气道上皮细胞、树突状细胞、巨噬细胞等产生IL-6、IL-8、GM-CSF等细胞因子，引起中性粒细胞趋化增加及凋亡下降；浸润的中性粒细胞活化可产生活性氧、MMP、NET等，引起气道上皮损伤，损伤的气道上皮可进一步分泌趋化因子及炎症介质等，加重气道炎症反应.IL：白细胞介素；GM-CSF：粒细胞-巨噬细胞集落刺激因子；TNF：肿瘤坏死因子；NET：中性粒细胞胞外诱捕网；MMP：基质金属蛋白酶；ECP：嗜酸性粒细胞阳离子蛋白；TSLP：胸腺基质淋巴细胞生成素；VEGF：血管内皮生长因子.
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