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Eotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity

Yang, Ming; Hogan, Simon; Mahalingam, Surendran; Pope, Samuel; Zimmermann, Nives; Fulkerson, Patricia; Dent, Lindsay; Young, Ian; Matthaei, Klaus; Rothenberg, Marc E; Foster, Paul S

Description

Background: Eotaxin-2 is a member of the eotaxin subfamily of CC chemokines that display eosinophil-specific, chemotactic properties and has been associated with allergic disorders. However, the contribution of eotaxin-2 to the development of defined pathogenic features of allergic disease remains to be defined. Objective: We sought to determine whether eotaxin-2 was a cofactor with IL-5 for the regulation of pulmonary eosinophilia and to identify the combined role of these molecules in the...[Show more]

dc.contributor.authorYang, Ming
dc.contributor.authorHogan, Simon
dc.contributor.authorMahalingam, Surendran
dc.contributor.authorPope, Samuel
dc.contributor.authorZimmermann, Nives
dc.contributor.authorFulkerson, Patricia
dc.contributor.authorDent, Lindsay
dc.contributor.authorYoung, Ian
dc.contributor.authorMatthaei, Klaus
dc.contributor.authorRothenberg, Marc E
dc.contributor.authorFoster, Paul S
dc.date.accessioned2015-12-13T23:14:15Z
dc.date.available2015-12-13T23:14:15Z
dc.identifier.issn0091-6749
dc.identifier.urihttp://hdl.handle.net/1885/88514
dc.description.abstractBackground: Eotaxin-2 is a member of the eotaxin subfamily of CC chemokines that display eosinophil-specific, chemotactic properties and has been associated with allergic disorders. However, the contribution of eotaxin-2 to the development of defined pathogenic features of allergic disease remains to be defined. Objective: We sought to determine whether eotaxin-2 was a cofactor with IL-5 for the regulation of pulmonary eosinophilia and to identify the combined role of these molecules in the induction of phenotypic characteristics of allergic lung disease. Methods: We instilled recombinant eotaxin-2 into the airways of wild-type mice that had been treated systemically with IL-5 or into IL-5-transgenic mice and characterized pulmonary eosinophil numbers, IL-13 production, and airway hyperreactivity (AHR) to methacholine. Mice deficient in the IL-4 receptor α-chain, IL-13, and signal transducers and activators of transcription 6 or mice treated with anti-CCR3 monoclonal antibody were also used. Results: Eotaxin-2 and IL-5 cooperatively promoted eosinophil accumulation, IL-13 production, and AHR to methacholine. Neither eotaxin-2 nor IL-5 alone induced these features of allergic disease. IL-13 production was critically dependent on eotaxin-2- and IL-5-regulated eosinophilia, which predisposed to the development of AHR. AHR was dependent on IL-13 and signaling through the IL-4R α-chain and signal transducers and activators of transcription 6 pathways and the presence of eosinophils in the lung. Conclusion: These investigations demonstrate important cooperativity between eotaxin-2, IL-5, and IL-13 signaling systems and eosinophils for the development of hallmark features of allergic disease of the lung.
dc.publisherMosby Inc
dc.sourceJournal of Allergy and Clinical Immunology
dc.subjectKeywords: beta chemokine; eotaxin; eotaxin 2; interleukin 13; interleukin 4 receptor; interleukin 4 receptor alpha; interleukin 5; methacholine; monoclonal antibody; monoclonal antibody ccr3; STAT6 protein; unclassified drug; allergic disease; animal cell; animal e Airway hyperreactivity; Cell recruitment; Eosinophils; Eotaxin-2; Interleukins-5 and -13; Mouse model
dc.titleEotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume112
dc.date.issued2003
local.identifier.absfor110701 - Allergy
local.identifier.ariespublicationMigratedxPub18222
local.type.statusPublished Version
local.contributor.affiliationYang, Ming, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationHogan, Simon, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMahalingam, Surendran, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationPope, Samuel, Cincinnati Children's Hospital Medical Center
local.contributor.affiliationZimmermann, Nives, University of Cincinnati
local.contributor.affiliationFulkerson, Patricia, University of Cincinnati
local.contributor.affiliationDent, Lindsay, University of Adelaide
local.contributor.affiliationYoung, Ian, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMatthaei, Klaus, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationRothenberg, Marc E, University of Cincinnati
local.contributor.affiliationFoster, Paul S, College of Medicine, Biology and Environment, ANU
local.bibliographicCitation.startpage935
local.bibliographicCitation.lastpage943
local.identifier.doi10.1016/j.jaci.2003.08.010
dc.date.updated2015-12-12T08:37:56Z
local.identifier.scopusID2-s2.0-0242467200
CollectionsANU Research Publications

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