A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation

Patricia C. Fulkerson, Christine A. Fischetti, Melissa L. McBride, Lynn M. Hassman, Simon P. Hogan, Marc E. Rothenberg

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

To clarify the role and regulation of eosinophils, we subjected several key eosinophil-related genetically engineered mice to a chronic model of allergic airway inflammation aiming to identify results that were independent of the genetic targeting strategy. In particular, mice with defects in eosinophil development (Δdbl-GATA) and eosinophil recruitment [mice deficient in CCR3 (CCR3 knockout) and mice deficient in both eotaxin-1 and eotaxin-2 (eotaxin-1/2 double knockout)] were subjected to Aspergillus fumigatus-induced allergic airway inflammation. Allergen-induced eosinophil recruitment into the airway was abolished by 98%, 94%, and 99% in eotaxin-1/2 double knockout, CCR3 knockout, and Δdbl-GATA mice, respectively. Importantly, allergen-induced type II T helper lymphocyte cytokine production was impaired in the lungs of eosinophil- and CCR3-deficient mice. The absence of eosinophils correlated with reduction in allergen-induced mucus production. Notably, by using global transcript expression profile analysis, a large subset (29%) of allergen-induced genes was eosinophil- and CCR3-dependent; pathways downstream from eosinophils were identified, including in situ activation of coagulation in the lung. In summary, we present multiple lines of independent evidence that eosinophils via CCR3 have a central role in chronic allergic airway disease.

Original languageEnglish
Pages (from-to)16418-16423
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number44
DOIs
StatePublished - Oct 31 2006

Keywords

  • Allergy
  • Asthma
  • Chemokine
  • Cytokine

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