Concurrent dual allergen exposure and its effects on airway hyperresponsiveness, inflammation and remodeling in mice

Abstract

SUMMARYExperimental mouse models of asthma have broadened our understanding of the mechanisms behind allergen-induced asthma. Typically, mouse models of allergic asthma explore responses to a single allergen; however, patients with asthma are frequently exposed to, and tend to be allergic to, more than one allergen. The aim of the current study was to develop a new and more relevant mouse model of asthma by measuring the functional, inflammatory and structural consequences of chronic exposure to a combination of two different allergens, ovalbumin (OVA) and house dust mite (HDM), in comparison with either allergen alone. BALB/c mice were sensitized and exposed to OVA, HDM or the combination of HDM and OVA for a period of 10 weeks. Following allergen exposure, airway responsiveness was measured using the flexiVent small animal ventilator, and mice were assessed for indices of airway inflammation and remodeling at both 24 hours and 4 weeks after the final allergen exposure. Mice exposed to the HDM-OVA combination exhibited increased numbers of inflammatory cells in the bronchoalveolar lavage (BAL) when compared with mice exposed to a single allergen. Mice exposed to HDM-OVA also exhibited an elevated level of lung tissue mast cells compared with mice exposed to a single allergen. Following the resolution of inflammatory events, mice exposed to the allergen combination displayed an elevation in the maximal degree of total respiratory resistance (Max R RS ) compared with mice exposed to a single allergen. Furthermore, trends for increases in indices of airway remodeling were observed in mice exposed to the allergen combination compared with a single allergen. Although concurrent exposure to HDM and OVA resulted in increased aspects of airway hyperresponsiveness, airway inflammation and airway remodeling when compared with exposure to each allergen alone, concurrent exposure did not result in a substantially more robust mouse model of allergic asthma than exposure to either allergen alone.

Lung Pathologies in a Chronic Inflammation Mouse Model Are Independent of Eosinophil Degranulation

“…This lack of concordance has typically been explained as either a limitation of mouse models (reviewed in Reference 54), shortcomings linked with available allergens administered to mice (55), and/or the allergen challenge protocols themselves (56,57). The data presented here provocatively showed that the loss of either MBP-1 or EPX had only nominal (if any) effects on many of the agedependent pulmonary pathologies occurring in I5/hE2 mice, including the breakdown of alveolar septa and pulmonary fibrosis.…”

Protease-Mediated House Dust Mite Allergen-Induced Reactive Oxygen Species Production by Neutrophils

“…It is widely accepted that HDM allergens and their specific IgE molecules bind to FcεRI, resulting in the activation of mast cells in HDM-sensitized individuals [16,17]. FcεRI has been shown to be expressed not only on the surface of mast cells and basophils but also on monocytes, platelets, eosinophils, dendritic cells, and Langerhans cells [18].…”

LPS Exposure in Early Life Protects Against Mucus Hypersecretion in Ovalbumin-Induced Asthma by Down-Regulation of the IL-13 and JAK-STAT6 Pathways

“…Mucous cell hyperplasia can be observed in the airways of almost every asthma patient and airway mucus plugging can affect the progression or aggravation in asthma or even lead to death [16]. However, there is no good treatment for mucus hypersecretion in asthma, thus specific drugs is required.…”