Regulation of airway hyperresponsiveness by calcitonin gene-related peptide in allergen sensitized and challenged mice

被引:58
作者
Dakhama, A [1 ]
Kanehiro, A [1 ]
Mäkelä, MJ [1 ]
Loader, JE [1 ]
Larsen, GL [1 ]
Gelfand, EW [1 ]
机构
[1] Natl Jewish Med & Res Ctr, Dept Pediat, Div Cell Biol & Pulm Med, Denver, CO 80206 USA
关键词
calcitonin gene-related peptide; airway hyperresponsiveness; allergen;
D O I
10.1164/ajrccm.165.8.2109058
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Sensory neuropeptides are localized to airway nerves and endocrine cells in both human and animal species and may participate in the development of airway inflammation and hyperresponsiveness (AHR). We used a mouse model to identify the changes that occur in calcitonin gene-related peptide (CGRP) expression in the airways during development of allergic inflammation and to investigate the potential role of this neuropeptide in modulating AHR. In sensitized mice, allergen challenge induced eosinophilic airway inflammation and AHR and resulted in considerable depletion of CGRP in neuroepithelial bodies and submucosal nerve plexuses without altering the overall density of airway nerve fibers. This depletion was subsequent to the development of airway inflammation and was prevented by anti-very late antigen-4 and anti-interleukin-5 treatments, which blocked airway eosinophilia and abolished AHR. Administration of CGRP to sensitized and challenged mice resulted in the normalization of airway responsiveness to inhaled methacholine, an effect that was neutralized by the receptor antagonist CGRP(8-37). These data demonstrate that replacement of CGRP following its depletion in allergic mice can reverse the changes in airway responsiveness and suggest that CGRP may have potential for the treatment of allergic AHR.
引用
收藏
页码:1137 / 1144
页数:8
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