chapter  15
44 Pages

Immunology of Eosinophilic Airway Inflammation: What the Animal Models Teach Us

Asthma is a chronic disorder of the airways in which symptoms such as shortness of breath, cough, and dyspnea are primarily related to airway obstruction. Increased airway responsiveness to provocative stimuli, termed airway hyperresponsiveness (AHR), and mucus hypersecretion by goblet cells are two of the principal causes of airway obstruction observed in asthma patients. Although asthma is a very complex disorder, our understanding of the pathogenesis of this diseasehas evolved substantially over the past decade.Following bronchial allergen exposure in atopic individuals, cross-linking of IgE on mast cells leads to immediate degranulation of mast cells and to synthesis of prostaglandins, leukotrienes, and cytokines (Fig. 1). Mast cells release a variety of preformed mediators known to directly constrict bronchial smooth muscle, irritate local nerve endings, dilate blood vessels, and increase leakage of plasma into the airways, leading to the occurrence of airway narrowing within 15min after challenge.This form of IgE-mediated allergy is classically called type I immediate hypersensitivity according to the classi¢cation of Gell and Coombs. In about 50% of challenged individuals, this early response is followed by a second, late bronchoconstrictive response that occurs 4^8 h after challenge and is characterized by tissue in¢ltration with mononuclear cells,Tcells, and eosinophils (Fig. 2). It is now believed that this late-phase response (LPR) of cellular in£ammation is mediated byT lymphocytes. Cytokines produced byT-helper (Th) cells promote the activation of in£ammatory cells and their recruitment to

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