Role of eosinophils and muscarinic receptors in paradoxical airway hyperreactivity associated with antigen challenge

This work identifies a novel inhibitory role for muscarinic receptors on human and guinea pig eosinophils and demonstrates their functional importance in vivo. Muscarinic signaling reduced eosinophil activation in vitro, while muscarinic blockade during antigen challenge increased eosinophil activation and vagally mediated airway hyperreactivity through mechanisms involving eosinophils and nerve growth factor (NGF). These findings reveal an alternative eosinophil‑dependent pathway for airway hyperreactivity that operates independently of M2 receptor dysfunction and may involve NGF‑driven neural plasticity. The results provide a mechanistic explanation for the limited effectiveness of anticholinergics in chronic asthma and highlight a bidirectional regulatory loop between parasympathetic nerves and eosinophils with clinical implications for asthma therapy.