Mast cell exocytosis in airway inflammation

The central role of mast cell activation in acute allergic reactions, including asthma, is well known (1,2). Increasingly, the participation of mast cells in perpetuating the chronic phase of allergic inflammation is being recognized (3,4). For these reasons, suppression of mast cell function is an important part of the treatment of allergic inflammation. However, protective roles of mast cells in initiating host defense against bacterial pathogens have recently been identified (5). Thus, therapeutic suppression of mast cell function should be selective so that maladaptive and troublesome allergic activation is eliminated without impairing essential defense functions. Mast cells are activated both through a specific IgE-mediated immune mechanism as well as through innate mechanisms mediated by complement (6), lectins (7), and other pathways (8). Since it appears that there is no important protective role of IgE-dependent immunity of the airways in contemporary Western societies (9), whereas the protective roles of mast cells appear to all be mediated by innate immune mechanisms (10), therapeutic targeting of IgE-dependent mast cell activation is an attractive strategy being pursued by several pharmaceutical companies (see Chap. 43). However, this strategy is only partially effective (11), possibly because mast cells are also activated by non-IgE-dependent mediators in allergic inflammation, such as adenosine (see Chap. 31). An alternative strategy would be to target signal Adachi et al.328.