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.

• Authors: Ramzi Fattouh, Amal Al-Garawi, Marcia Fattouh, Katherine Arias, Tina D Walker, Susanna Goncharova, Anthony J Coyle, Alison A Humbles, Manel Jordana
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 183 Issue 2 Pg. 179-88 (Jan 15 2011) ISSN: 1535-4970 [Electronic] United States
• PMID: 20732990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin E
• Collagen

Topics

• Animals
• Bronchoalveolar Lavage Fluid (immunology)
• Collagen (immunology, metabolism)
• Disease Models, Animal
• Eosinophils (immunology)
• Female
• Immunoglobulin E (blood, immunology)
• Inflammation (etiology, immunology)
• Mice
• Mice, Inbred BALB C
• Pyroglyphidae (immunology)
• Respiratory Hypersensitivity (complications, immunology, metabolism)
• Respiratory Mucosa (immunology, metabolism)