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CLC number: R562.2

On-line Access: 2015-07-03

Received: 2014-10-23

Revision Accepted: 2015-02-01

Crosschecked: 2015-06-15

Cited: 2

Clicked: 1637

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Hui-ying Wang

http://orcid.org/0000-0001-8630-2592

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Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.7 P.622-631

http://doi.org/10.1631/jzus.B1400285


Anti-CD69 monoclonal antibody treatment inhibits airway inflammation in a mouse model of asthma


Author(s):  Hui-ying Wang, Yu Dai, Jiao-li Wang, Xu-yan Yang, Xin-guo Jiang

Affiliation(s):  Department of Allergy, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; more

Corresponding email(s):   marywang@zju.edu.cn

Key Words:  Cluster of differentiation 69 (CD69), Eosinophil, Interleukin-5 (IL-5), Asthma


Hui-ying Wang, Yu Dai, Jiao-li Wang, Xu-yan Yang, Xin-guo Jiang. Anti-CD69 monoclonal antibody treatment inhibits airway inflammation in a mouse model of asthma[J]. Journal of Zhejiang University Science B, 2015, 16(7): 622-631.

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author="Hui-ying Wang, Yu Dai, Jiao-li Wang, Xu-yan Yang, Xin-guo Jiang",
journal="Journal of Zhejiang University Science B",
volume="16",
number="7",
pages="622-631",
year="2015",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1400285"
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%A Hui-ying Wang
%A Yu Dai
%A Jiao-li Wang
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A1 - Hui-ying Wang
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DOI - 10.1631/jzus.B1400285


Abstract: 
Objective: Airway inflammation and airway hyper-responsiveness (AHR) are principle pathological manifestations of asthma. cluster of differentiation 69 (CD69) is a well-known co-stimulatory factor associated with the activation, proliferation as well as apoptosis of immune cells. This study aims to examine the effect of anti-CD69 monoclonal antibody (mAb) on the pathophysiology of a mouse model of asthma. Methods: A murine model of ovalbumin (OVA)-induced allergic airway inflammation was used in this study. Briefly, mice were injected with 20 μg chicken OVA intraperitoneally on Days 0 and 14, followed by aerosol provocation with 1% (0.01 g/ml) OVA on Days 24, 25, and 26. Anti-CD69 mAb or isotype IgG was injected intraperitoneally after OVA challenge; dexamethasone (DXM) was administrated either before or after OVA challenge. AHR, mucus production, and eosinophil infiltration in the peribronchial area were examined. The levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) in bronchoalveolar lavage fluid (BALF) were also assayed as indices of airway inflammation on Day 28 following OVA injection. Results: Pretreatment with DXM together with anti-CD69 mAb treatment after OVA provocation completely inhibited AHR, eosinophil infiltration and mucus overproduction, and significantly reduced BALF IL-5. However, treatment with DXM alone after OVA challenge only partially inhibited AHR, eosinophil infiltration and mucus overproduction, and did not diminish BALF IL-5. Treatment with either DXM or anti-CD69 mAb did not alter the concentration of BALF GM-CSF. Conclusions: Anti-CD69 mAb treatment inhibits established airway inflammation as effectively as DXM pretreatment. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma and its exacerbation.

抗CD69单克隆抗体对哮喘小鼠的气道炎症抑制作用研究

目的:气道慢性炎症和高反应性是哮喘最主要的病理生理表现,CD69是一种与免疫细胞活化、增殖及凋亡密切相关的共刺激分子,本研究旨在观察抗CD69单克隆抗体在哮喘小鼠模型中抑制气道炎症和高反应性的作用及机制探讨。
创新点:(1)与大多数关于哮喘的药物研究多为造模前提前用药以阻断炎症的进展相比,本研究将抗CD69单抗作用于气道已经形成的炎症,与临床上哮喘的治疗更接近;(2)抗CD69单抗的独特作用在于它特异性地作用于气道活化的炎症细胞,与已有的哮喘药物以糖皮质激素相比,可能的全身反应少。
方法:鸡卵白蛋白致敏激发制备哮喘模型(图1),Buxco系统测试哮喘小鼠的气道高反应性(图6)。
结论:抗CD69单克隆抗体可抑制哮喘小鼠已经形成的气道炎症,其作用效果与地塞米松预处理相当。本研究为临床哮喘的急性发作治疗和管理提供了新的可能靶点。

关键词:分化抗原簇69(CD69);白介素-5;哮喘;嗜酸性粒细胞

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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