Eosinophils are Dispensable for Allergic Remodeling and Immunity in a Model of House Dust Mite-Induced Airway Disease.

Authors: Fattouh, R  Al-Garawi, A  Fattouh, M  Arias, K  Walker, TD  Goncharova, S  Coyle, AJ  Humbles, AA  Jordana, M 
Citation: Fattouh R, etal., Am J Respir Crit Care Med. 2010 Aug 23.
Pubmed: (View Article at PubMed) PMID:20732990
DOI: Full-text: DOI:10.1164/rccm.200905-0736OC

RATIONALE: Current thinking accredits eosinophils with preeminent contributions to allergic airway responses including a major role in the development of airway remodeling, a process thought to significantly contribute to airway dysfunction. However, direct evidence in support of this notion is limited and often controversial. OBJECTIVES: Here, we elucidated the requirement for eosinophils in the generation of allergic sensitization, airway inflammation and remodeling in a model involving chronic respiratory exposure to house dust mite (HDM). METHODS: We employed three methods to selectively eliminate eosinophils, a depleting antibody (anti-CCR3) and two strains of eosinophil-deficient mice (DeltadblGATA and the transgenic line PHIL). MEASUREMENTS AND MAIN RESULTS: We report that anti-CCR3 treatment markedly reduced pulmonary eosinophilia (>80%) over the course of HDM exposure, but had no effect on the remaining inflammatory response, extent of lung Th2 cells or development of remodeling-associated changes including subepithelial collagen deposition and smooth muscle thickening. In addition, we observed that, despite the complete absence of eosinophils, HDM-exposed GATA mice mounted robust airway/lung inflammation and hyperresponsiveness, and a remodeling response equivalent to that observed in wild-type mice. Moreover, these mice had similar serum HDM-specific IgE levels and Th2-associated splenocyte cytokine production as HDM-exposed wild-type controls. Similar observations were made in PHIL eosinophil-deficient mice subjected to chronic HDM exposure, although slight decreases in airway mononuclear cells, but not lung Th2 cells, and remodeling were noted. CONCLUSIONS: Collectively, these data demonstrate that, at variance with the prevailing paradigm, eosinophils play negligible roles in the generation of HDM-induced allergic immunity and airway remodeling.


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CRRD Object Information
CRRD ID: 4145617
Created: 2010-11-10
Species: All species
Last Modified: 2010-11-10
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.