Mucosal exposure to cockroach extract induces allergic sensitization and allergic airway inflammation

Narcy G Arizmendi,Harissios Vliagoftis,Lakshmi Puttagunta,Muhammad Asaduzzaman,Courtney Davidson,Paul Forsythe,Melanie Abel,Khalil Karimi

doi:10.1186/1710-1492-7-22

Narcy G Arizmendi, Harissios Vliagoftis + Show 6 more

Open Access

https://doi.org/10.1186/1710-1492-7-22

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Abstract

BackgroundAllergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens. Allergic sensitization may lead to the development of asthma, which is characterized by chronic airway inflammation. The objective of this study is to describe in detail a model of mucosal exposure to cockroach allergens in the absence of an exogenous adjuvant.MethodsCockroach extract (CE) was administered to mice intranasally (i.n.) daily for 5 days, and 5 days later mice were challenged with CE for 4 consecutive days. A second group received CE i.n. for 3 weeks. Airway hyperresponsiveness (AHR) was assessed 24 h after the last allergen exposure. Allergic airway inflammation was assessed by BAL and lung histology 48 h after the last allergen exposure. Antigen-specific antibodies were assessed in serum. Lungs were excised from mice from measurement of cytokines and chemokines in whole lung lysate.ResultsMucosal exposure of Balb/c mice to cockroach extract induced airway eosinophilic inflammation, AHR and cockroach-specific IgG1; however, AHR to methacholine was absent in the long term group. Lung histology showed patchy, multicentric damage with inflammatory infiltrates at the airways in both groups. Lungs from mice from the short term group showed increased IL-4, CCL11, CXCL1 and CCL2 protein levels. IL4 and CXCL1 were also increased in the BAL of cockroach-sensitized mice in the short-term protocol.ConclusionsMucosal exposure to cockroach extract in the absence of adjuvant induces allergic airway sensitization characterized by AHR, the presence of Th2 cytokines in the lung and eosinophils in the airways.

Highlights

Allergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens
We have developed a model for mucosal sensitization of mice using whole body cockroach extract
To extend the duration of exposure to allergen we sensitized another group of mice with 50 μg of Cockroach extract (CE) intranasally 5 days a week for 3 weeks, and for 2 consecutive days on the fourth week before evaluation for Airway hyperresponsiveness (AHR) and allergic airway inflammation as before (Figure 1A - long term protocol)

Summary

Introduction

Allergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens. Allergic sensitization may lead to the development of asthma, which is characterized by chronic airway inflammation. Animal models of asthma have a number of limitations, including the physiological relevance of the allergen used and potential differences between humans and animals in the development of allergic immune responses. There is controversy regarding the utility of murine models of asthma as predictors of the response of human asthma to therapeutics [3]. Some of these difficulties arise from inadequacies of the murine models we use. Other differences come from the way we use murine models and the kinds of responses we expect them to predict

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