Eosinophils and CCR3 regulate interleukin-13 transgene-induced pulmonary remodeling

Am J Pathol. 2006 Dec;169(6):2117-26. doi: 10.2353/ajpath.2006.060617.


Interleukin (IL)-13 transgene overexpression in the lung induces features of chronic inflammatory lung disorders, including an eosinophil-rich inflammatory cell infiltration, airway hyper-reactivity, and remodeling of the airway (eg, subepithelial fibrosis, goblet cell metaplasia, and smooth muscle hypertrophy and hyperplasia). Here, we aimed to define the role of eosinophils and eosinophil signaling molecules [eg, eotaxins and CC chemokine receptor (CCR) 3] in IL-13-mediated airway disease. To accomplish this, we mated IL-13-inducible lung transgenic mice with mice deficient in eosinophil chemoattractant molecules (eotaxin-1, eotaxin-2, and their receptor CCR3) and with mice genetically deficient in eosinophils (Deltadbl-GATA). We report that in the absence of eotaxin-2 or CCR3, there was a profound reduction in IL-13-induced eosinophil recruitment into the lung lumen. In contrast, in the absence of eotaxin-1, there was a fourfold increase in IL-13-mediated eosinophil recruitment into the airway. IL-13 transgenic mice deficient in CCR3 had a 98% reduction in lung eosinophils. Furthermore, the reduction in pulmonary eosinophils correlated with attenuation in IL-13-induced mucus cell metaplasia and collagen deposition. Mechanistic analysis identified alterations in pulmonary protease and transforming growth factor-beta1 expression in eosinophil-deficient mice. Taken together, these data definitively identify a functional contribution by eosinophils on the effects of chronic IL-13 expression in the lung.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Asthma / chemically induced
  • Asthma / immunology
  • Asthma / metabolism
  • Chemokine CCL11
  • Chemokines, CC / metabolism
  • Collagen / metabolism
  • Eosinophils / physiology*
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interleukin-13 / genetics
  • Interleukin-13 / physiology*
  • Ligands
  • Lung / enzymology
  • Lung / metabolism
  • Lung / pathology*
  • Mice
  • Mice, Transgenic
  • Mucus / metabolism
  • Peptide Hydrolases / metabolism
  • Pulmonary Eosinophilia / immunology
  • Pulmonary Eosinophilia / metabolism
  • Pulmonary Eosinophilia / pathology*
  • Receptors, CCR3
  • Receptors, Chemokine / metabolism*
  • Receptors, Chemokine / physiology


  • Ccl11 protein, mouse
  • Ccr3 protein, mouse
  • Chemokine CCL11
  • Chemokines, CC
  • Interleukin-13
  • Ligands
  • Receptors, CCR3
  • Receptors, Chemokine
  • Collagen
  • Peptide Hydrolases