Localization of eosinophils to airway nerves and effect on neuronal M₂ muscarinic receptor function

Neuronal M₂ muscarinic receptors inhibit acetylcholine release from pulmonary parasympathetic nerves but are dysfunctional in antigen-challenged animals and asthmatics. Depletion of pulmonary eosinophils protects M₂ receptor function in antigen-challenged guinea pigs. Therefore, the association of eosinophils with airway nerves was investigated. Nerve- associated eosinophils were significantly increased in challenged animals compared with controls (0.75 ± 0.05 vs. 0.28 ± 0.05 eosinophils/nerve). In antigen-challenged animals, eosinophil density was greatest around airway nerves, suggesting recruitment to the nerves. M₂ receptor function was inversely correlated with the number of eosinophils per nerve, thus eosinophils are associated with airway nerves in antigen-challenged guinea pigs, where they impair M₂ receptor function. In airways from three patients with fatal asthma, 196 of 637 eosinophils (30%) were associated with nerves and release of eosinophil major basic protein was evident; conversely, in three control patients 1 of 11 (9%) eosinophils were in contact with nerves. Thus eosinophils and their granule proteins are also seen in association with airway nerves in patients with asthma.