Eotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity.
J Allergy Clin Immunol
; 112(5): 935-43, 2003 Nov.
Article
em En
| MEDLINE
| ID: mdl-14610483
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 alpha-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 alpha-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.
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Bases de dados:
MEDLINE
Assunto principal:
Eosinofilia Pulmonar
/
Interleucina-5
/
Hiper-Reatividade Brônquica
/
Interleucina-13
/
Quimiocinas CC
/
Pulmão
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2003
Tipo de documento:
Article