McMillan, S.J. & Lloyd, C.M. Prolonged allergen challenge in mice leads to persistent airway remodelling. Clin. Exp. Allergy 34, 497-507

Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, London, UK.
Clinical & Experimental Allergy (Impact Factor: 4.77). 04/2004; 34(3):497-507. DOI: 10.1111/j.1365-2222.2004.01895.x
Source: PubMed


Inflammatory infiltrates, airway hyper-responsiveness, goblet cell hyperplasia and subepithelial thickening are characteristic of chronic asthma. Current animal models of allergen-induced airway inflammation generally concentrate on the acute inflammation following allergen exposure and fail to mimic all of these features.
The aim of this study was to use a murine model of prolonged allergen-induced airway inflammation in order to characterize the cells and molecules involved in the ensuing airway remodelling. Moreover, we investigated whether remodelling persists in the absence of continued allergen challenge.
Acute pulmonary eosinophilia and airways hyper-reactivity were induced after six serial allergen challenges in sensitized mice (acute phase). Mice were subsequently challenged three times a week with ovalbumin (OVA) (chronic phase) up to day 55. To investigate the persistence of pathology, one group of mice were left for another 4 weeks without further allergen challenge (day 80).
The extended OVA challenge protocol caused significant airway remodelling, which was absent in the acute phase. Specifically, remodelling was characterized by deposition of collagen as well as airway smooth muscle and goblet cell hyperplasia. Importantly, these airway changes, together with tissue eosinophilia were sustained in the absence of further allergen challenge. Examination of cytokines revealed a dramatic up-regulation of IL-4 and tumour growth factor-beta1 during the chronic phase. Interestingly, while IL-4 levels were significantly increased during the chronic phase, levels of IL-13 fell. Levels of the Th1-associated cytokine IFN-gamma also increased during the chronic phase.
In conclusion, we have demonstrated that prolonged allergen challenge results in persistent airway wall remodelling.

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Available from: Clare M Lloyd, Mar 24, 2014
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    • "A chronic model of asthma was established according to a modification of a model of prolonged allergen-induced airway inflammation described in [2]. Mice were exposed daily to 5% OVA aerosol in saline or saline only using a Pari LC Star nebuliser (PARI GmbH, Starnberg, Germany) in an aerosol cabin for 20 min between days 17 and 23. "
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    • "There are three isoforms of TGF-β in the normal human lung, and TGF-β1 is associated with bronchial epithelial cells, smooth muscle cells, fibroblast-like cells, and the airway extracellular matrix (ECM) [38–41]. TGF-β1 level is increased in BALF of asthmatic patients [42], and asthmatic animal models also show increased levels of TGF-β1 in BALF and tissue [43, 44]. Mice treated with anti-TGF-β antibody significantly reduce the deposition of peribronchial ECM, proliferation of airway smooth muscle cell, and mucus production in lung [45]. "
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    • "Our study expands on these investigations by performing comprehensive analysis of both inflammatory and remodelling parameters. It has been proposed that the cessation of allergen exposure does not completely attenuate airway remodelling [1], [14], [31], [32]. In the studies by McMillan et al. and by Kumar et al. four weeks of allergen cessation was not sufficient to fully resolve airway remodelling [14], [31]. "
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