A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation.
Proc Natl Acad Sci U S A
; 103(44): 16418-23, 2006 Oct 31.
Article
in En
| MEDLINE
| ID: mdl-17060636
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 (Deltadbl-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 Deltadbl-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bronchial Hyperreactivity
/
Receptors, Chemokine
/
Chemokines, CC
/
Eosinophils
Type of study:
Prognostic_studies
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2006
Document type:
Article
Affiliation country:
Estados Unidos