A Study On The Immunologic Mechanisms Of Asthma Exacerbation Induced By Chronic Aspergillus Fumigatus Exposure

Chapter 1: Effects of Aspergillus fumigatus Spor es Inhalation on Air way Inflammation, Air way Responsiveness and Total Ser um IgE in Asthmatic RatsObjective: To explore the effects of Aspergillus fumigatus(A. fumigatus) exposure on airway eosinophilic inflammation, airway hyper-responsiveness and total serum IgE in asthmatic rats.Methods: Eighteen male Wistar rats were randomly divided into three groups: a normal control group, an asthmatic model group, and an A. fumigatus spores inhalation group. The rats in asthmatic model group and the A. fumigatus spores inhalation group were sensititized and challenged with ovalbumin to establish asthmatic model. After establishment of asthmatic model, the rats in the A. fumigatus spores inhalation group were treated with repeated A. fumigatus spores inhalation. Subsequently, airway responsiveness/ sensitivity to Mch(methacholine), airway inflammation and the level of total serum IgE were assessed and compared among the three groups.Results:Compared with the asthmatic rats, the rats treated with A. fumigatus inhalation showed higher airway responsiveness(Penh/ baseline value was substantially increased, especially at the Mch concentration of 12.5, 25 and 50 mg/ml), increased inflammatory cells infiltration in pulmonary tissue and increased total serum IgE level(P < 0. 05). Most importantly, serum IgE level was found in close relationship with PC100 which was defined as the dose of Mch causing 100% increase of Penh(enhance pause) value without Mch challenge(r=- 0. 873, P <0. 01). Total serum IgE level was also closely related to the percentage of eosinophils in BALF(r =0. 937, P <0. 01).Conclusions : Repeated A. fumigatus spore inhalation aggravates airway eosinophilic inflammation, bronchial hyperresponsiveness and serum IgE level in asthmatic rats. IgE may play an important role in facilitating the development of eosinophilic inflammation and bronchial responsiveness. Chapter 2: Regulation of glucocor ticoid r eceptor expr ession by chr onic stimulation with Aspergillus fumigatus spor es pr omotes r at asthmatic exacer bationObjective: Whether Aspergillus fumigatus effects the expression of glucocorticoid receptors(GR) in the asthmatic rat lung and leads to steroid resistance for asthmatic exacerbation remains unknown. The aim of this study was to investigate the change of GR expression after A. fumigatus stimulation in a rat asthmatic model.Methods: A classical ovalbumin(OVA)-induced rat asthma model was first established, followed by chronic inhalational stimulation with A. fumigatus spores. The fungi spore-induced asthmatic exacerbation was evaluated by airway inflammation and hyperresponsiveness, and the GR expression by real-time quantitative polymerase chain reaction and Western blot.Results: Repeated stimulation with A. fumigates spores significantly enhanced preexisting OVA-induced airway inflammation and hyperresponsiveness(P<0.05). There is significantly decreased GR expression(P<0.05) in the asthmatic rats treated with repeated Aspergillus fumigatus spores stimulation.Conclusion: The A. fumigatus spore stimulation decreased the GR expression in the asthmatic rat lung, which may contribute to asthmatic exacerbation and steroid-resistance.