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Pathogenesis of Murine Experimental Allergic Rhinitis: A Study of Local and Systemic Consequences of IL-5 Deficiency

Saito, Hiroko; Matsumoto, Koichiro; Denburg, Avram; Crawford, Lynn; Ellis, Russ; Inman, Mark; Sehmi, Roma; Takatsu, Kiyoshi; Matthaei, Klaus; Denburg, Judah

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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...[Show more]

dc.contributor.authorSaito, Hiroko
dc.contributor.authorMatsumoto, Koichiro
dc.contributor.authorDenburg, Avram
dc.contributor.authorCrawford, Lynn
dc.contributor.authorEllis, Russ
dc.contributor.authorInman, Mark
dc.contributor.authorSehmi, Roma
dc.contributor.authorTakatsu, Kiyoshi
dc.contributor.authorMatthaei, Klaus
dc.contributor.authorDenburg, Judah
dc.date.accessioned2015-12-10T23:22:13Z
dc.identifier.issn0022-1767
dc.identifier.urihttp://hdl.handle.net/1885/66442
dc.description.abstractRecent 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.
dc.publisherAmerican Association of Immunologists
dc.sourceJournal of Immunology
dc.subjectKeywords: CD4 antigen; histamine; interleukin 5; ovalbumin; recombinant interleukin 5; allergic rhinitis; allergy; animal cell; animal experiment; animal model; animal tissue; article; asthma; basophil; bronchus hyperreactivity; cell count; cell differentiation; ce
dc.titlePathogenesis of Murine Experimental Allergic Rhinitis: A Study of Local and Systemic Consequences of IL-5 Deficiency
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume168
dc.date.issued2002
local.identifier.absfor110705 - Humoural Immunology and Immunochemistry
local.identifier.ariespublicationMigratedxPub1284
local.type.statusPublished Version
local.contributor.affiliationSaito, Hiroko, McMaster University
local.contributor.affiliationMatsumoto, Koichiro, McMaster University
local.contributor.affiliationDenburg, Avram, McMaster University
local.contributor.affiliationCrawford, Lynn, McMaster University
local.contributor.affiliationEllis, Russ, McMaster University
local.contributor.affiliationInman, Mark, McMaster University
local.contributor.affiliationSehmi, Roma, McMaster University
local.contributor.affiliationTakatsu, Kiyoshi, University of Tokyo
local.contributor.affiliationMatthaei, Klaus, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationDenburg, Judah, McMaster University
local.description.embargo2037-12-31
local.bibliographicCitation.issue(6)
local.bibliographicCitation.startpage3017
local.bibliographicCitation.lastpage3023
dc.date.updated2015-12-10T10:29:14Z
local.identifier.scopusID2-s2.0-0037087251
CollectionsANU Research Publications

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