Eotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity
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Yang, Ming; Hogan, Simon; Mahalingam, Surendran; Pope, Samuel; Zimmermann, Nives; Fulkerson, Patricia; Dent, Lindsay; Young, Ian; Matthaei, Klaus; Rothenberg, Marc E; Foster, Paul S
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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.author | Yang, Ming | |
---|---|---|
dc.contributor.author | Hogan, Simon | |
dc.contributor.author | Mahalingam, Surendran | |
dc.contributor.author | Pope, Samuel | |
dc.contributor.author | Zimmermann, Nives | |
dc.contributor.author | Fulkerson, Patricia | |
dc.contributor.author | Dent, Lindsay | |
dc.contributor.author | Young, Ian | |
dc.contributor.author | Matthaei, Klaus | |
dc.contributor.author | Rothenberg, Marc E | |
dc.contributor.author | Foster, Paul S | |
dc.date.accessioned | 2015-12-13T23:14:15Z | |
dc.date.available | 2015-12-13T23:14:15Z | |
dc.identifier.issn | 0091-6749 | |
dc.identifier.uri | http://hdl.handle.net/1885/88514 | |
dc.description.abstract | 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 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.publisher | Mosby Inc | |
dc.source | Journal of Allergy and Clinical Immunology | |
dc.subject | Keywords: 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.title | Eotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.description.refereed | Yes | |
local.identifier.citationvolume | 112 | |
dc.date.issued | 2003 | |
local.identifier.absfor | 110701 - Allergy | |
local.identifier.ariespublication | MigratedxPub18222 | |
local.type.status | Published Version | |
local.contributor.affiliation | Yang, Ming, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Hogan, Simon, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Mahalingam, Surendran, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Pope, Samuel, Cincinnati Children's Hospital Medical Center | |
local.contributor.affiliation | Zimmermann, Nives, University of Cincinnati | |
local.contributor.affiliation | Fulkerson, Patricia, University of Cincinnati | |
local.contributor.affiliation | Dent, Lindsay, University of Adelaide | |
local.contributor.affiliation | Young, Ian, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Matthaei, Klaus, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Rothenberg, Marc E, University of Cincinnati | |
local.contributor.affiliation | Foster, Paul S, College of Medicine, Biology and Environment, ANU | |
local.bibliographicCitation.startpage | 935 | |
local.bibliographicCitation.lastpage | 943 | |
local.identifier.doi | 10.1016/j.jaci.2003.08.010 | |
dc.date.updated | 2015-12-12T08:37:56Z | |
local.identifier.scopusID | 2-s2.0-0242467200 | |
Collections | ANU Research Publications |
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