Eosinophils and airway nerves in asthma

In the lungs, neuronal M-2 muscarinic receptors limit the release of acetyl choline from postganglionic cholinergic nerves. However, these receptors ar e not functional under certain circumstances in animal models of hyperreact ivity such as occurs after exposure of sensitised animals to an allergen or during a respiratory tract virus infection. This loss of M-2 receptor func tion leads to an increase in acetylcholine release from cholinergic nerves and thus is a mechanism for the vagally mediated hyperreactivity seen in th ese animals. Studies in animal models of hyperreactivity have shown that eo sinophils localise to the airway nerves of sensitised animals after antigen challenge. Inhibiting this localisation of eosinophils either with an anti body to the eosinophil survival cytokine IL-5 or the eosinophil adhesion mo lecule VLA-4 prevents loss of M-2 muscarinic receptor function. It is Likel y that eosinophil MBP is responsible for the loss of M-2 receptor function, since inhibiting eosinophil MBP with an antibody or neutralising MBP with heparin prevents this loss of function. These data are also supported by li gand binding studies where it has been shown that eosinophil MBP is an allo steric antagonist at neuronal M-2 muscarinic receptors. Loss of function of lung neuronal M-2 muscarinic receptors may also occur under certain circum stances in patients with asthma, although the mechanisms are not yet establ ished.