Localization of eosinophils to airway nerves and effect on neuronal M-2 muscarinic receptor function

Neuronal M-2 muscarinic receptors inhibit acetylcholine release from pulmonary parasympathetic nerves but are dysfunctional in antigen-challenged animals and asthmatics. Depletion of pulmonary eosinophils protects M-2 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. Mt 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 M-2 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.