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Eosinophils are dispensable for allergic remodeling and immunity in a model of house dust mite-induced airway disease.

Abstract：

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: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 used three methods to selectively eliminate eosinophils, a depleting antibody (anti-CCR3), and two strains of eosinophil-deficient mice (ΔdblGATA and the transgenic line PHIL). MEASUREMENTS AND MAIN RESULTS:Anti-CCR3 treatment markedly reduced pulmonary eosinophilia (> 80%) over the course of HDM exposure but had no effect on the remaining inflammatory response, the extent of lung Th2 cells, or the development of remodeling-associated changes, including subepithelial collagen deposition and smooth muscle thickening. In addition, we observed that, despite the absence of eosinophils, HDM-exposed GATA mice mounted robust airway and lung inflammation and hyperresponsiveness and showed 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 control mice. 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.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Fattouh R,Al-Garawi A,Fattouh M,Arias K,Walker TD,Goncharova S,Coyle AJ,Humbles AA,Jordana M

doi

10.1164/rccm.200905-0736OC

subject

Has Abstract

pub_date

2011-01-15 00:00:00

pages

179-88

issue

eissn

1073-449X

issn

1535-4970

pii

200905-0736OC

journal_volume

183

pub_type

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Eosinophils are dispensable for allergic remodeling and immunity in a model of house dust mite-induced airway disease.