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Role of Interleukin-5 and Eosinophils in Allergen-Induced Airway Remodeling in Mice

Department of Pharmacology, Gifu Pharmaceutical University, Gifu; Department of Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; and Allergy Research Laboratory, Centre de Recherche du Centre Hospitalier Université de Montréal (CHUM), Notre-Dame Hospital, University of Montreal, Montreal, Québec, Canada

Address correspondence to: Prof. Hiroichi Nagai, Ph.D., Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan. E-mail: nagai{at}gifu-pu.ac.jp

Asthma is a chronic inflammatory disease characterized by variable bronchial obstruction, hyperresponsiveness, and by tissue damage known as airway remodeling. In the present study we demonstrate that interleukin (IL)-5 plays an obligatory role in the airway remodeling observed in experimental asthma. BALB/c mice sensitized by intraperitoneal injections of ovalbumin and exposed daily to aerosol of ovalbumin for up to 3 wk, develop eosinophilic infiltration of the bronchi and subepithelial and peribronchial fibrosis. The lesions are associated with increased amounts of hydroxyproline in the lungs and elevated levels of eosinophils and transforming growth factor (TGF)-ß1 in the bronchoalveolar lavage fluid. After 1 wk of allergen challenge, TGF-ß is mainly produced by eosinophils accumulated in the peribronchial and perivascular lesions. At a later stage of the disease, the main source of TGF-ß is myofibroblasts, identified by -smooth muscle actin mAb. We show that all these lesions, including fibrosis, are abolished in sensitized and allergen-exposed IL-5 receptor–null mice, whereas they are markedly accentuated in IL-5 transgenic animals. More importantly, treatment of wild-type mice with neutralizing anti–IL-5 antibody, administered before each allergen challenge, almost completely prevented subepithelial and peribronchial fibrosis. These findings demonstrated that eosinophils are involved in allergen-induced subepithelial and peribronchial fibrosis probably by producing a fibrogenic factor, TGF-ß1.

Abbreviations: bronchoalveolar lavage, BAL • BAL fluid, BALF • hydroxyproline, HP • interleukin, IL • ovalbumin, OVA • phosphate-buffered saline, PBS • receptor chain, R • transgenic, Tg • transforming growth factor, TGF

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