Saito, H., Matsumoto, K., Denburg, A. E., Crawford, L., Ellis, R., Inman, M. D., Sehmi, R., Takatsu, K., Matthaei, K. I. and Denburg, J. A. (2002) Pathogenesis of murine experimental allergic rhinitis: a study of local and systemic consequences of IL-5 deficiency. Journal of Immunology, 168(6), pp. 3017-3023. (doi: 10.4049/jimmunol.168.6.3017)
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Publisher's URL: http://dx.doi.org/10.4049/jimmunol.168.6.3017
Abstract
Recent studies have demonstrated an important role for IL-5-dependent bone marrow eosinophil progenitors in allergic inflammation. However, studies using anti-IL-5 mAbs in human asthmatics have failed to suppress lower airway hyperresponsiveness despite suppression of eosinophilia; therefore, it is critical to examine the role of IL-5 and bone marrow responses in the pathogenesis of allergic airway disease. To do this, we studied the effects of IL-5 deficiency (IL-5−/−) on bone marrow function as well as clinical and local events, using an established experimental murine model of allergic rhinitis. Age-matched IL-5+/+ and IL-5−/− BALB/c mice were sensitized to OVA followed by 2 wk of daily OVA intranasal challenge. IL-5−/− OVA-sensitized mice had significantly higher nasal mucosal CD4+ cells and basophilic cell counts as well as nasal symptoms and histamine hyperresponsiveness than the nonsensitized group; however, there was no eosinophilia in either nasal mucosa or bone marrow; significantly lower numbers of eosinophil/basophil CFU and maturing CFU eosinophils in the presence of recombinant mouse IL-5 in vitro; and significantly lower expression of IL-5Rα on bone marrow CD34+CD45+ progenitor cells in IL-5−/− mice. These findings suggest that IL-5 is required for normal bone marrow eosinophilopoiesis, in response to specific Ag sensitization, during the development of experimental allergic rhinitis. However, the results also suggest that suppression of the IL-5-eosinophil pathway in this model of allergic rhinitis may not completely suppress clinical symptoms or nasal histamine hyperresponsiveness, because of the existence of other cytokine-progenitor pathways that may induce and maintain the presence of other inflammatory cell populations.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Stewart, Ms Lynn |
Authors: | Saito, H., Matsumoto, K., Denburg, A. E., Crawford, L., Ellis, R., Inman, M. D., Sehmi, R., Takatsu, K., Matthaei, K. I., and Denburg, J. A. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Journal of Immunology |
Publisher: | American Association of Immunologists |
ISSN: | 0022-1767 |
ISSN (Online): | 1550-6606 |
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