Mechanisms of cholinergic hyperfunction induced by IgE in human airways

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In this study, we examined the effect of IgE on human airway cholinergic nerve function both in vitro and in vivo.In vitro study, human bronchi were obtained from 20 patients undergoing lung resection. Cholinergic contractile responses were induced by electrical field stimulation (EFS) or exogenous acetylcholine (ACh). Incubation with IgE significantly enhanced EFS-induced bronchial contraction and ACh release compared with those of control tissues. Autoreceptor M2 function was also impaired by IgE incubation. These in vitro results suggest that IgE itself can enhance cholinergic contraction via ACh release from the nerves possibly by M2 dysfunction.In vivo study, 36 allergic rhinitis patients [17 with low serum IgE (titer was (]SY.ltoreq.[) 250) and 19 with high serum IgE (250<) ] without lower respiratory tract diseases and 11 healthy subjects were enrolled in the study. We compared their bronchodilator responses to inhalation anti-cholinergic and beta<@D22@>D2-adrenergic agents. Air … More way caliber was assessed by forced expiratory volume in one second (FEV<@D21@>D2). %FEV<@D21@>D2 values of all patients were greater than 80% , but were negatively correlated with serum IgE levels (P<0.01). Submaximal doses of the anti-cholinergic agent caused small but significant bronchodilation in both healthy and allergic rhinitis subjects. The increase in FEV<@D21@>D2 was significantly greater in allergic rhinitis patients with high serum IgE(155 (]SY.+-。[)20ml mean(]SY.+-。[)SEM,P<0.05) than in healthy subjects (64(]SY.+-。[))21 ml) and those with allergic rhinitis but low serum IgE (82 (]SY.+-。[)) 21 ml, P<0.05). In contrast, the effects of the beta<@D22@>D2-adrenergic agent were not significantly different among the three groups. We concluded that higher serum IgE levels were correlated with lower FEV<@D21@>D2 values, and that the anti-cholinergic agent but not the beta<@D22@>D2-adrenergic agent causes more pronounced bronchodilation in high IgE subjects than in low IgE allergic rhinitis patients and healthy subjects. These in vivo data suggest that serum IgE may be one of the factors that determine the airway caliber via cholinergic mechanisms. Less