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Comparison of allergic lung disease in three mouse strains after systemic or mucosal sensitization with ovalbumin antigen

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Abstract

Murine models of allergic lung disease have many similar traits to asthma in humans and can be used to investigate mechanisms of allergic sensitization and susceptibility factors associated with disease severity. The purpose of this study was to determine strain differences in allergic airway inflammation, immunoglobulin production, and changes in respiratory responses between systemic and mucosal sensitization routes in BALB/cJ, FVB/NJ, and C57BL/6J, and to provide correlations between immune and pathophysiological endpoints. After a single intranasal ovalbumin (OVA) challenge, all three strains of mice systemically sensitized with OVA and adjuvant exhibited higher airflow limitation than non-sensitized mice. No changes were seen in mice that were pre-sensitized via the nose with OVA. Systemic sensitization resulted in an elevated response to methacholine (MCH) in BALB/cJ and FVB/NJ mice and elevated total and OVA-specific IgE levels and pulmonary eosinophils in all three strains. The mucosal sensitization and challenge produced weaker responses in the same general pattern with the C57BL/6J strain producing less serum IgE, IL5, IL13, and eosinophils in lung fluid than the other two strains. The converse was found for IL6 where the C57BL/6J mice had more than twice the amount of this cytokine. The results show that the FVB/NJ and BALB/cJ mice are higher Th2-responders than the C57BL/6J mice and that the levels of pulmonary eosinophilia and cytokines did not fully track with MCH responsiveness. These differences illustrate the need to assess multiple endpoints to provide clearer associations between immune responses and type and severity of allergic lung disease.

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Acknowledgments & EPA disclosure

We thank Mary Daniels, Elizabeth Boykin James Lehmann and Judy Richards for their technical assistance. The project described was supported by CEMALB of UNC-CA through a cooperative agreement with the U.S. EPA (#R82952201). Its content are solely the responsibility of the authors and do not necessarily represent the official views of the U.S. EPA. This paper has been reviewed by the U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use.

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Authors and Affiliations

  1. Center for Environmental Medicine, Asthma & Lung Biology, The University of North Carolina at Chapel Hill, 104 Mason Farm Road, CB 7310, Chapel Hill, NC, 27599-7310, USA

    Weiyan Zhu

  2. Immunotoxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environment Protection Agency, Research Triangle Park, Durham, NC, 27711, USA

    M. Ian Gilmour

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  1. Weiyan Zhu
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  2. M. Ian Gilmour
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Correspondence to M. Ian Gilmour.

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Zhu, W., Gilmour, M.I. Comparison of allergic lung disease in three mouse strains after systemic or mucosal sensitization with ovalbumin antigen. Immunogenetics 61, 199–207 (2009). https://doi.org/10.1007/s00251-008-0353-8

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  • DOI: https://doi.org/10.1007/s00251-008-0353-8

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