Effects of prolonged Aspergillus fumigatus spores inhalation on airway inflammation and remodeling in rats with chronic obstructive pulmonary disease_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

GAO Fusheng , LONG Fei , QI Huihui , ZHANG Yi ,  JIN Xianqiao

Department of Respiratory Medicine，Shanghai First People’s Hospital Affiliated to Shanghai Jiaotong Univerisity.Shanghai，200080，China Corresponding author：JIN Xian-qiao，E-mail：jinxianqiao@hotmail.com;

Corresponding author：

JIN Xianqiao, Email: jinxianqiao@hotmail.com

Keywords：

Chronic obstructive pulmonary disease; Aspergillus fumigatus; Spore; Airway inflammation; Airway remodeling

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Objective To explore the effects of prolonged Aspergillus fumigatus spores inhalation on airway inflammation and remodeling in rats with chronic obstructive pulmonary disease（COPD）.Methods Fifty Wistar rats were randomly divided into group A，B，C，D and E，(n=10 in each group) and group E was served as normal control.In group A，B，C and D，COPD models were established by intratracheal administration of lipopolysaccharide (LPS) combined with cigarette smoke exposure.The rats in group A，B and C were given intranasal inhalation of 1×106cfu spores，1×103cfu spores and 100 mL saline twice a week for consecutive 5 weeks，respectively，while the rats in group D were given no treatment.Bronchoalveolar lavage fluid(BALF) were collected for total and differential cell count，and interleukin-8（IL-8） and transforming growth factor-b(TGF-b) concentration measurement.The pathologic changes of lung tissue were observed by HE，PAS and Masson stainings.Results Pathological changes characteristic of COPD were found in group D.The total cell count，the percentage of neutrophile and lymphocyte in BALF in group A and B were higher than those in group C and D(all P lt;0.01).IL-8 and TGF-b in BALF in group A and B were higher than those in group C and D(all P lt;0.01).The pathologic score of airway inflammation in group A was higher than those in group B，C and D(all P lt;0.01)：The thickness of airway wall(WAt/Pbm) and airway smooth muscles(WAm/Pbm)，the collagen deposition in the total airway wall(WCt/Pbm) and in the outer airway wall(WCo/Pbm) and the percentage of goblet cells to epithelial cells in group A and B were higher than those in group C and D(all P lt;0.01).In group A and B，IL-8 was positively correlated with the percentage of neutrophile(r=0.856，P lt;0.01)，the pathologic score of airway inflammation(r＝0.884，P lt;0.01)，and the percentage of goblet cells to epithelial cells (r=0.702，P lt;0.05)，respectively.TGF-b was positively correlated with WAt/Pbm，WCt/Pbm，WCo/Pbm and the ratio of goblet cells to epithelial cells (r=0.706，P lt;0.05：r=0.802，P lt;0.01：r=0.876，P lt;0.01：r=0.713，P lt;0.05).Conclusion Prolonged inhalation of Aspergillus fumigatus spores can aggravate the airway inflammation and remodeling in rats with COPD.

Citation： GAO Fusheng,LONG Fei,QI Huihui,ZHANG Yi,JIN Xianqiao. Effects of prolonged Aspergillus fumigatus spores inhalation on airway inflammation and remodeling in rats with chronic obstructive pulmonary disease. Chinese Journal of Respiratory and Critical Care Medicine, 2008, 08(3): 205-209. doi: Copy

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7.	Tang CM，Cohen J，Krausz T，et al.The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis.Infect Immun，1993，61：1650-1656.
8.	钟小宁，白晶，施焕中，等.慢性支气管炎与肺气肿大鼠气道炎症与重塑的实验研究.中华结核和呼吸杂志，2003，26：750-755.
9.	Palmans E，Kips JC，Pauwels RA.Prolonged allergen exposure induces structural airway changes in sensitized rats.Am J Respir Crit Care Med，2000，161：627-635.
10.	Latge JP.Aspergillus fumigatus and aspergillosis.Clin Microbiol Rev，1999，12：310-350.
11.	Rivera A，Hohl T，Pamer EG.Immune response to Aspergillus fumigatus infections.Biol Blood Marrow Transplant，2006，12：47-49.
12.	Garnacho-Monterol J，Amaya-Villar R，Ortiz-Leyba C，et al.Isolation of Aspergillus spp.from the respiratory tract in critically ill patients：risk factors，clinical presentation and outcome.Crit Care，2005，9：R191-R199.
13.	Engelhart S，Hanfland J，Glasmacher A，et al.Impact of portable air filtration units on exposure of hematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions.J Hosp Infect，2003，54：300-304.

1. Wu L，Skinner SJ，Lambie N，et al.Immunohistochemical staining for Chlamydia pneumoniae is increased in lung tissue from subjects with chronic obstructive pulmonary disease.Am J Respir Crit Care Med，2000，162：1148-1151.
2. Retamales I，Elliott WM，Meshi B，et al.Amplification of inflammation in emphysema and its association with latent adenoviral infection.Am J Respir Crit Care Med，2001，164：469-473.
3. Wilkinson TM，Patel IS，Wilks M，et al.Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med，2003，167：1090-1095.
4. Kauffman HF，Tomee JF，van de Riet MA，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.
5. 宋一平，崔德健，茅培英，等.慢性阻塞性肺疾病大鼠模型气道重塑及生长因子的研究.中华结核和呼吸杂志，2001，24：283-287．.
6. 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，2007，6：185-190.
7. Tang CM，Cohen J，Krausz T，et al.The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis.Infect Immun，1993，61：1650-1656.
8. 钟小宁，白晶，施焕中，等.慢性支气管炎与肺气肿大鼠气道炎症与重塑的实验研究.中华结核和呼吸杂志，2003，26：750-755.
9. Palmans E，Kips JC，Pauwels RA.Prolonged allergen exposure induces structural airway changes in sensitized rats.Am J Respir Crit Care Med，2000，161：627-635.
10. Latge JP.Aspergillus fumigatus and aspergillosis.Clin Microbiol Rev，1999，12：310-350.
11. Rivera A，Hohl T，Pamer EG.Immune response to Aspergillus fumigatus infections.Biol Blood Marrow Transplant，2006，12：47-49.
12. Garnacho-Monterol J，Amaya-Villar R，Ortiz-Leyba C，et al.Isolation of Aspergillus spp.from the respiratory tract in critically ill patients：risk factors，clinical presentation and outcome.Crit Care，2005，9：R191-R199.
13. Engelhart S，Hanfland J，Glasmacher A，et al.Impact of portable air filtration units on exposure of hematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions.J Hosp Infect，2003，54：300-304.

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