Effects of <i>Aspergillus fumigatus</i> on Airway Inflammation, Airway Responsiveness and Total Serum IgE in Asthmatic Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZhengMingrui ¹ , LiuHaixia ² , DangYajie ¹ ,  JinXianqiao ³

1. Department of Respiratory Medicine, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China;
2. ;
3. ;

Corresponding author：

JinXianqiao, Email: jinxianqiao@aliyun.com

Keywords：

Aspergillus fumigatus; Asthma; IgE; Airway hyperresponsiveness; Eosinophils

DOI：

10.7507/1671-6205.2015008

Video：

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Objective To explore the effects of Aspergillus fumigatus (A. fumigatus) on airway inflammation, airway responsiveness and total serum IgE in asthmatic rats. Methods Eighteen male Wistar rats were divided into three groups randomly, ie. a normal control group, an asthmatic model group, and an A. fumigatus group. The rats in the model group and the A.fumigatus group were sensititized and challenged with ovalbumin to establish asthmatic model. After establishment of asthmatic model, the rats in the A. fumigatus group were treated with chronic A. fumigatus spores inhalation. Subsequently, airway responsiveness/sensitivity to methacholine(Ach), levels of serum IgE and airway inflammation were assessed and compared among three groups. Results Compared with the asthmatic rats, the rats treated with A. fumigatus showed higher airway responsiveness (Penh/baselin value was significantly increased at the Mch concentration of 12.5, 25 and 50 mg/mL), increased inflammatory cells infiltration in pulmonary tissue slices and increased serum IgE level (P < 0.05). Most importantly, serum IgE level was detected in close relationship with PC100 which was defined as the dose of Mch causing 100% increase of enhance pause (Penh) value without Mch challenge (r=-0.873, P < 0.01). Serum IgE level was also closely related to the percentage of eosinophils in bronchoalveolar lavage fluid (r=0.937, P < 0.01). Conclusions Chronic A. fumigatus inhalation aggravates airway inflammation, bronchial hyperresponsiveness and serum IgE level in asthma. IgE may play an important role in facilitating the development of bronchial responsiveness and eosinophilic inflammation.

Citation： ZhengMingrui, LiuHaixia, DangYajie, JinXianqiao. Effects of Aspergillus fumigatus on Airway Inflammation, Airway Responsiveness and Total Serum IgE in Asthmatic Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2015, 14(1): 27-31. doi: 10.7507/1671-6205.2015008 Copy

1.	Knutsen AP, Bush RK, Demain JG, et al.Fungi and allergic lower respiratory tract diseases.J Allergy Clin Immunol, 2012, 129:280-291.
2.	Pandey S, Hoselton SA, Schuh JM.The impact of Aspergillus fumigatus viability and sensitization to its allergens on the murine allergic asthma phenotype.Biomed Res Int, 2013, 2013:619614.
3.	Fairs A, Agbetile J, Hargadon B, et al.IgE sensitization to aspergillus fumigatus is associated with reduced lung function in asthma.Am J Respir Crit Care Med, 2010, 182:1362-1368.
4.	Chaudhary N, Marr KA.Impact of Aspergillus fumigatus in allergic airway diseases.Clin Transl Allergy, 2011, 1:4.
5.	Guilbert TW, Denlinger LC.Role of infection in the development and exacerbation of asthma.Expert Rev Respir Med, 2010, 4:71-83.
6.	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.
7.	李斌恺, 赖克方, 洪燕华, 等.支气管哮喘小鼠气道反应性无创检测方法的建立.中华哮喘杂志(电子版), 2009, 3:243-247.
8.	Wark PA, Tooze M, Powell H, et al.Viral and bacterial infection in acute asthma and chronic obstructive pulmonary disease increases the risk of readmission.Respirology, 2013, 18:996-1002.
9.	Greenberg S.Asthma exacerbations:Predisposing factors and prediction rules.Curr Opin Allergy Clin Immunol, 2013, 13:225-236.
10.	Gao FS, Qiao JO, Zhang Y, et al.Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodelling in asthmatic rats.Respirology, 2009, 14:360-370.
11.	高福生, 金先桥, 乔建瓯, 等.慢性烟曲霉暴露对哮喘大鼠气道上皮细胞损伤及表皮生长因子受体表达的影响.中国呼吸与危重监护杂志, 2010, 9:115-121.
12.	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.
13.	Liu H, Zheng M, Qiao J, et al.Role of prostaglandin d2/crth2 pathway on asthma exacerbation induced by Aspergillus fumigatus.Immunology, 2014, 142:78-88.
14.	李明华, 殷凯生, 朱桂丽, 主编.哮喘病学.北京:人民卫生出版社, 2005, 185.
15.	Zubairi AB, Azam I, Awan S, et al.Association of airborne Aspergillus with asthma exacerbation in southern Pakistan.Asia Pac Allergy, 2014, 4:91-98.
16.	Kim BS, Jin HS, Kim HB, et al.Airway hyperresponsiveness is associated with total serum immunoglobulin E and sensitization to aeroallergens in Korean adolescents.Pediatr Pulmonol, 2010, 45:1220-1227.
17.	Burrows B, Sears MR, Flannery EM, et al.Relationships of bronchial responsiveness assessed by methacholine to serum IgE, lung function, symptoms, and diagnoses in 11-year-old New Zealand children.J Allergy Clin Immunol, 1992, 90:376-385.
18.	Kono M, Mochizuki H, Arakawa H, et al.Age-dependent relationship between bronchial hyperresponsiveness to methacholine and total serum IgE level in asthmatic children.Ann Allergy Asthma Immunol, 2001, 87:33-38.
19.	Sears MR, Burrows B, Flannery EM, et al.Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children.N Engl J Med, 1991, 325:1067-1071.
20.	Mizutani N, Nabe T, Yoshino S.IgE/antigen-mediated enhancement of IgE production is a mechanism underlying the exacerbation of airway inflammation and remodeling in mice.Immunology, 2014, 189:897-902.
21.	Coyle AJ, Wagner K, Bertrand C, et al.Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production:inhibition by a non-anaphylactogenic anti-IgE antibody.J Exp Med, 1996, 183:1303-1310.
22.	Mizutani N, Nabe T, Yoshino S.Interleukin-33 and alveolar macrophages contribute to the mechanisms underlying the exacerbation of IgE-mediated airway inflammation and remodelling in mice.Immunology, 2013, 139:205-218.

1. Knutsen AP, Bush RK, Demain JG, et al.Fungi and allergic lower respiratory tract diseases.J Allergy Clin Immunol, 2012, 129:280-291.
2. Pandey S, Hoselton SA, Schuh JM.The impact of Aspergillus fumigatus viability and sensitization to its allergens on the murine allergic asthma phenotype.Biomed Res Int, 2013, 2013:619614.
3. Fairs A, Agbetile J, Hargadon B, et al.IgE sensitization to aspergillus fumigatus is associated with reduced lung function in asthma.Am J Respir Crit Care Med, 2010, 182:1362-1368.
4. Chaudhary N, Marr KA.Impact of Aspergillus fumigatus in allergic airway diseases.Clin Transl Allergy, 2011, 1:4.
5. Guilbert TW, Denlinger LC.Role of infection in the development and exacerbation of asthma.Expert Rev Respir Med, 2010, 4:71-83.
6. 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.
7. 李斌恺, 赖克方, 洪燕华, 等.支气管哮喘小鼠气道反应性无创检测方法的建立.中华哮喘杂志(电子版), 2009, 3:243-247.
8. Wark PA, Tooze M, Powell H, et al.Viral and bacterial infection in acute asthma and chronic obstructive pulmonary disease increases the risk of readmission.Respirology, 2013, 18:996-1002.
9. Greenberg S.Asthma exacerbations:Predisposing factors and prediction rules.Curr Opin Allergy Clin Immunol, 2013, 13:225-236.
10. Gao FS, Qiao JO, Zhang Y, et al.Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodelling in asthmatic rats.Respirology, 2009, 14:360-370.
11. 高福生, 金先桥, 乔建瓯, 等.慢性烟曲霉暴露对哮喘大鼠气道上皮细胞损伤及表皮生长因子受体表达的影响.中国呼吸与危重监护杂志, 2010, 9:115-121.
12. 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.
13. Liu H, Zheng M, Qiao J, et al.Role of prostaglandin d2/crth2 pathway on asthma exacerbation induced by Aspergillus fumigatus.Immunology, 2014, 142:78-88.
14. 李明华, 殷凯生, 朱桂丽, 主编.哮喘病学.北京:人民卫生出版社, 2005, 185.
15. Zubairi AB, Azam I, Awan S, et al.Association of airborne Aspergillus with asthma exacerbation in southern Pakistan.Asia Pac Allergy, 2014, 4:91-98.
16. Kim BS, Jin HS, Kim HB, et al.Airway hyperresponsiveness is associated with total serum immunoglobulin E and sensitization to aeroallergens in Korean adolescents.Pediatr Pulmonol, 2010, 45:1220-1227.
17. Burrows B, Sears MR, Flannery EM, et al.Relationships of bronchial responsiveness assessed by methacholine to serum IgE, lung function, symptoms, and diagnoses in 11-year-old New Zealand children.J Allergy Clin Immunol, 1992, 90:376-385.
18. Kono M, Mochizuki H, Arakawa H, et al.Age-dependent relationship between bronchial hyperresponsiveness to methacholine and total serum IgE level in asthmatic children.Ann Allergy Asthma Immunol, 2001, 87:33-38.
19. Sears MR, Burrows B, Flannery EM, et al.Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children.N Engl J Med, 1991, 325:1067-1071.
20. Mizutani N, Nabe T, Yoshino S.IgE/antigen-mediated enhancement of IgE production is a mechanism underlying the exacerbation of airway inflammation and remodeling in mice.Immunology, 2014, 189:897-902.
21. Coyle AJ, Wagner K, Bertrand C, et al.Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production:inhibition by a non-anaphylactogenic anti-IgE antibody.J Exp Med, 1996, 183:1303-1310.
22. Mizutani N, Nabe T, Yoshino S.Interleukin-33 and alveolar macrophages contribute to the mechanisms underlying the exacerbation of IgE-mediated airway inflammation and remodelling in mice.Immunology, 2013, 139:205-218.

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Effects of Aspergillus fumigatus on Airway Inflammation, Airway Responsiveness and Total Serum IgE in Asthmatic Rats

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