The Influence of Chronic <i>Aspergillus fumigatus</i> Exposure on Airway Eosinophilia and Hyperresponsiveness in Rat Asthma Model_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LiuHaixia ¹ ,  JinXianqiao ¹ ^# , ZhengMingrui ¹ , QiaoJianou ²

1. Department of Respiratory Medicine, Shanghai First People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China;
2. ;

Corresponding author：

JinXianqiao, Email: jxq.sh.cn@gmail.com

Keywords：

Airway responsiveness; Asthma; Eosinophil; Rat model; Aspergillus fumigatus

DOI：

10.7507/1671-6205.2014008

Video：

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Objective To explore the effect of Aspergillus fumigatus on airway eosinophilia and hyperresponsiveness in rat model of chronic asthma. Methods Wistar rats were sensitized by intraperitoneal injections with ovalbumin (OVA) followed by chronic inhalation of nebulized OVA or physiologic saline. Rats were administered via the airways with placebo or aerosolized Aspergillus fumigatus spores suspension mimicking chronic Aspergillus fumigatus exposure. The Penh after acetylcholine provocation was detected using WBP system. The concentrations of IL-5 and eotaxin in BALF were measured by ELISA. The extents of eosinophil infiltration were evaluated on hematoxylin and eosin-stained(HE) and Wright-Giemsa stained BALF cells smear. Results Aspergillus fumigatus worsened allergic airway inflammation in OVA-challenged rats,as evidenced by enhanced bronchial responsiveness to inhaled acetylcholine and increased bronchial eosinophilia. Elevated airway eosinophilia corresponded with higher levels of IL-5 and eotaxin in the Aspergillus Fumigatus exposure group. Aspergillus fumigatus,however,did not affect bronchial responses,numbers of eosinophils,IL-5 and eotaxin levels in saline challenged mice. Conclusion The Results show that chronic Aspergillus fumigatus exposure aggravates eosinophilic airway inflammation in asthma rats by enhancing IL-5 and eotaxin production. Aspergillus fumigatus also increases bronchial hyperresponsiveness in asthma rats.

Citation： LiuHaixia, JinXianqiao, ZhengMingrui, QiaoJianou. The Influence of Chronic Aspergillus fumigatus Exposure on Airway Eosinophilia and Hyperresponsiveness in Rat Asthma Model. Chinese Journal of Respiratory and Critical Care Medicine, 2014, 13(1): 28-33. doi: 10.7507/1671-6205.2014008 Copy

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2.	Peng T,Hao L,Madri JA,et al. Role of C5 in the development of airway inflammation,airway hyper-responsiveness,and ongoing airway response. J Clin Invest,2005,115:1590-1600.
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9.	Kurup VP,Choi H,Murali PS,et al. IgE and eosinophil regulation in a murine model of allergic aspergillosis. J Leukoc Biol,1994,56:593-598.
10.	Kauffman HF,Tomee JFC,Marjolein A,et al. Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. J Allergy Clin Immunol,2000,105:1185-1193.
11.	张志红,Kauffman HF,Noordhoek J,等.烟曲霉菌对呼吸道上皮细胞的作用.安徽医科大学学报,2005,40:334-337.
12.	王妍,龙飞,祁卉卉,等. 烟曲霉菌孢子对哮喘大鼠气道炎症和气道反应性的影响.中国呼吸与危重监护杂志,2007,6:185-196.
13.	Foster PS,Rosenberg HF,Asquith KL,et al. Targeting eosinophils in asthma. Curr Mol Med,2008,8:585-590.
14.	Egan RW,Umland SP,Cuss FM,et al. Biology of interleukin-5 and its relevance to allergic disease. Allergy,1996,51:71-81.
15.	Leckie MJ,Brinke A,Khan J,et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils,airway hyper-responsiveness and the late asthmatic response. Lancet,2000,356:2144-2148.
16.	Flood-Page PT,Menzies-Gow AN,KayAB,et al. Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med,2003,167:199-204.
17.	Flood-Page P,Swenson C,Faiferman I,et al. International Mepolizumab StudyGroup. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med,2007,176:1062-1071.
18.	Williams DL. Overview of (1-->3)-beta-D-glucan immunobiology. Mediators Inflamm,1997,6:247-250.
19.	Agarwal R,Khan A,Aggarwal AN,et al. Clinical relevance of peripheral blood eosinophil count in allergic bronchopulmonary aspergillosis.J Infect Public Health,2011,4:235-243.
20.	Greenberger PA.Chapter 18:Allergic bronchopulmonary aspergillosis. Allergy Asthma Pro,2012,33 Suppl 1:S61-S63.

1. Green RH,Brightling CE,McKenna S,et al. Asthma exacerbations and sputum eosinophil counts:a randomised controlled trial. Lancet,2002,360:1715-1721.
2. Peng T,Hao L,Madri JA,et al. Role of C5 in the development of airway inflammation,airway hyper-responsiveness,and ongoing airway response. J Clin Invest,2005,115:1590-1600.
3. Denning DW,O'Driscoll BR,Hogaboam CM,et al. The link between fungi and severe asthma:a summary of the evidence. Eur Respir J,2006,27:615-626.
4. Gao FS,Qiao JO,Jin XQ,et al. Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodeling in asthmatic rats. Respirology,2009,14:360-370.
5. 龙飞,高福生,丁星,等. 烟曲霉菌提取物对人支气管上皮细胞粒-巨噬细胞刺激因子表达的影响. 第二军医大学学报,2008,29:917-920.
6. 高福生,龙飞,祁卉卉,等. 吸入烟曲霉孢子对哮喘大鼠气道上皮重构和MUC5AC表达的影响. 上海交通大学学报:医学版,2008,28:1095-1099.
7. Wasylnka JA,Moore MM. Adhesion of Aspergillus species to extracellular matrix proteins:Evidence for involvement of negatively charged carbohydrates on the conidial surface. Infect Immun,2000,68:3377-3384.
8. Madan T,Priyadarsiny P,Vaid M,et al. Use of a synthetic peptide epitope of Asp f 1,a major allergen or antigen of Aspergillus fumigatus,for improved immunodiagnosis of allergic bronchopulmonary aspergillosis. Clin Diagn Lab Immunol,2004,11:552-558.
9. Kurup VP,Choi H,Murali PS,et al. IgE and eosinophil regulation in a murine model of allergic aspergillosis. J Leukoc Biol,1994,56:593-598.
10. Kauffman HF,Tomee JFC,Marjolein A,et al. Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. J Allergy Clin Immunol,2000,105:1185-1193.
11. 张志红,Kauffman HF,Noordhoek J,等.烟曲霉菌对呼吸道上皮细胞的作用.安徽医科大学学报,2005,40:334-337.
12. 王妍,龙飞,祁卉卉,等. 烟曲霉菌孢子对哮喘大鼠气道炎症和气道反应性的影响.中国呼吸与危重监护杂志,2007,6:185-196.
13. Foster PS,Rosenberg HF,Asquith KL,et al. Targeting eosinophils in asthma. Curr Mol Med,2008,8:585-590.
14. Egan RW,Umland SP,Cuss FM,et al. Biology of interleukin-5 and its relevance to allergic disease. Allergy,1996,51:71-81.
15. Leckie MJ,Brinke A,Khan J,et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils,airway hyper-responsiveness and the late asthmatic response. Lancet,2000,356:2144-2148.
16. Flood-Page PT,Menzies-Gow AN,KayAB,et al. Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med,2003,167:199-204.
17. Flood-Page P,Swenson C,Faiferman I,et al. International Mepolizumab StudyGroup. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med,2007,176:1062-1071.
18. Williams DL. Overview of (1-->3)-beta-D-glucan immunobiology. Mediators Inflamm,1997,6:247-250.
19. Agarwal R,Khan A,Aggarwal AN,et al. Clinical relevance of peripheral blood eosinophil count in allergic bronchopulmonary aspergillosis.J Infect Public Health,2011,4:235-243.
20. Greenberger PA.Chapter 18:Allergic bronchopulmonary aspergillosis. Allergy Asthma Pro,2012,33 Suppl 1:S61-S63.

Chinese Journal of Respiratory and Critical Care Medicine

The Influence of Chronic Aspergillus fumigatus Exposure on Airway Eosinophilia and Hyperresponsiveness in Rat Asthma Model

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