LOCALIZATION OF EOSINOPHILS TO AIRWAY NERVES AND EFFECT ON NEURONAL M-2 MUSCARINIC RECEPTOR FUNCTION

Neuronal M-2 muscarinic receptors inhibit acetylcholine release from p ulmonary parasympathetic nerves but are dysfunctional in antigen-chall enged animals and asthmatics. Depletion of pulmonary eosinophils prote cts 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 challenge d animals compared with controls (0.75 +/- 0.05 vs. 0.28 +/- 0.05 eosi nophils/nerve). In antigen-challenged animals, eosinophil density was greatest around airway nerves, suggesting recruitment to the nerves. M t receptor function was inversely correlated with the number of eosino phils per nerve, thus eosinophils are associated with airway nerves in antigen-challenged guinea pigs, where they impair M-2 receptor functi on. In airways from three patients with fatal asthma, 196 of 637 eosin ophils (30%) were associated with nerves, and release of eosinophil ma jor 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 ne rves in patients with asthma.