A sthma affects millions of people worldwide, and its re-ported incidence is increasing dramatically in many developed nations; the human and economic costs of this disorder, in morbidity, health care expenses, lost productivity, and, most tragically, even mortality, are staggering (1, 2). It is now generally thought that asthma is a syndrome, typically characterized by the three cardinal features of intermittent and reversible airway obstruction, airway hyperresponsiveness, and airway inflammation, that may arise as a result of interactions between multiple genetic and environmental factors (1-4). Nevertheless, most cases of the disorder (the so-called" atopic" or" allergic" asthma) occur in subjects whom also exhibit immediate hypersensitivity responses to defined environmental allergens, and challenge of the airways of these subjects with such allergens can produce reversible airway obstruction (1-5). It is also known that the overall incidence of asthma in several different populations exhibits a strong positive correlation with serum concentrations of IgE, which, in humans, is the main (if not the only) Ig isotype that can mediate immediate hypersensitivity responses (1, 5). Moreover, it has been demonstrated that mast cells, derivatives of hematopoietic precursor cells that undergo their terminal stages of differentiation/maturation in the peripheral tissues in which they reside (6, 7), express cell surface receptors (Fcd~ I) that permit them to bind the Fc portion of IgE with high affinity, and also that such lgE-sensitized mast cells, upon encounter with specific antigen that is recognized by their FcdkI-bound IgE, secrete a broad panel of bioactive mediators, including:(a) preformed mediators that are stored in the cell's cytoplasmic granules (eg, histamine, heparin, and neutral proteases),(b) newly synthesized lipid products (eg, prosta-glandin D 2 and leukotriene C4), and (c) diverse cytokines (4, 6, 8, 9). Finally, several lines of evidence indicate that many of these potentially mast cell-derived mediators can promote reversible airway obstruction, bronchial hyperreactivity, and/or airway inflammation (see reviews in references 2-4, 8, and 9).

In light of these findings, it was once widely believed that atopic or allergic asthma is a disease that primarily reflects the consequences of IgE-and allergen-dependent mast cell activation. Yet several observations have called into question the central role of mast cells in asthma. These include the demonstration that additional cell types, including eosinophils (10) and Th2 lymphocytes (11), both of which are well represented in the chronic inflammatory