期刊
FUNGAL BIOLOGY
卷 115, 期 1, 页码 21-29出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.funbio.2010.09.013
关键词
Allergic asthma; Aspergillus fumigatus; Inhalation challenge model
类别
资金
- NIH/NCRR [2P20 RR015566]
- NIH/NIAID [1R15AI69061]
- NDSU (NSF) [HRD-0811239]
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR015566] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R15AI069061] Funding Source: NIH RePORTER
Allergic asthma is a debilitating disease of the airways characterized by airway hyperresponsiveness, eosinophilic inflammation, goblet cell metaplasia with associated mucus hypersecretion, and airway wall remodelling events, particularly subepithelial fibrosis and smooth muscle cell hyperplasia. Animal models that accurately mimic these hallmarks of allergic airways disease are critical for studying mechanisms associated with the cellular and structural changes that lead to disease pathogenesis. Aspergillus fumigatus, is a common aeroallergen of human asthmatics. The intratracheal (IT) delivery of A. fumigatus conidia into the airways of sensitized mice has been described as a model of allergic disease. Here, we compared the IT model with a newly developed inhalation (IH) challenge model. The IH model allowed multiple fungal exposures, which resulted in an exacerbation to the allergic asthma phenotype. Increased recruitment of eosinophils and lymphocytes, the hallmark leukocytes of asthma, was noted with the IH model as compared to the IT model in which macrophages and neutrophils were more prominent. Immunoglobulin E (IgE) production was significantly greater after IH challenge, while that of IgG(2a) was higher after IT challenge. Airway wall remodelling was pronounced in IH-treated mice, particularly after multiple allergen challenges. Although the IT model may be appropriate for the examination of the played by innate cells in the acute response to fungus, it fails to consistently reproduce the chronic remodelling hallmarks of allergic asthma. The ability of the IH challenge to mimic these characteristics recommends it as a model suited to study these important events. (C) 2010 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
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