Leukotrienes and other mast cell mediators cause asthmatic airway obstruction

Summary From an evolutionary perspective, bronchoconstriction is a highly conserved mechanism for defence against stimuli that are noxious for the lung and airways. The presence of mast cells in all layers of the airways makes them ideally situated to function as sensors of environmental changes that require such a host defence reaction. In addition to being activated by high affinity IgE receptors, many other trigger factors are known to activate signal transduction pathways leading to mast cell degranulation. This includes changes in the physical and chemical composition of the environment, exposure to endotoxin and other microbial factors acting on Toll‐like receptors [ 1 ], intake of certain drugs and in particular virtually all nonsteroidal anti‐inflammatory drugs (NSAIDs) in subjects with the peculiar syndrome aspirin‐intolerant asthma (AIA) [ 2 ]. Irrespective of the trigger, the consequence of mast cell activation is release of biologically active smooth muscle stimulating mediators as well as the secretion of cytokines, chemotactic factors and enzymes that are believed to trigger further cascades contributing to long‐term tissue remodelling and chronic airway inflammation.