Eosinophil recruitment to the airway nerves

Increased vagal reflexes contribute to bronchoconstriction in asthma, Antig en challenge of sensitized animals induces vagal hyperresponsiveness. This review will discuss the evidence that eosinophils increase release of acety lcholine from the parasympathetic nerves. After antigen challenge, eosinoph ils are actively recruited to the airway nerves, possibly through expressio n of chemotactic substances and adhesion molecules by the nerves. Tachykini ns acting on neurokinin 1 receptors activate the eosinophils. Activated eos inophils release eosinophil major basic protein (MBP), which is an endogeno us antagonist for Mt muscarinic receptors. The M-2 muscarinic receptors on the parasympathetic nerves in the lungs normally inhibit release of acetylc holine. When Mt receptors are blocked by MBP, acetylcholine release is incr eased, resulting in hyperresponsiveness. Neutralization of MBP with polyani onic substances restores Mt receptor function and eliminates hyperresponsiv eness. Antibodies to MBP prevent Mt receptor dysfunction and hyperresponsiv eness, as do antibodies to the adhesion molecule very late antigen 4, which prevent eosinophil migration. A low dose of dexamethasone, which does not affect total eosinophil influx into the lungs and airways, prevents eosinop hils from clustering around the nerves and prevents antigen-induced Mt dysf unction and hyperresponsiveness. Furthermore, animal studies show that vira l infections, which are important precipitants of asthma attacks, and expos ure to air pollutants such as ozone can also activate airway eosinophils, l eading to a chain of events similar to that seen after antigen challenge. F inally, a similar clustering of eosinophils around airway nerves, as well a s release of MBP onto the nerves, is seen in fatal asthma, suggesting that similar mechanisms may be involved in human airway hyperresponsiveness.