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

Azzeddine Dakhama, Arihiko Kanehiro, Mika J. Mäkelä, Joan E. Loader, Gary L. Larsen, Erwin W. Gelfand

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1137-1144
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume165
Issue number8
DOIs
Publication statusPublished - Apr 15 2002

Keywords

  • Airway hyperresponsiveness
  • Allergen
  • Calcitonin gene-related peptide

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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