title: Regulation of airway hyperresponsiveness by calcitonin gene-related peptide in allergen sensitized and challenged mice.
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.
authors.affiliation: Division of Cell Biology and Pulmonary Medicine, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Arihiko
authors.initials: A
authors.lastname: Kanehiro
authors.forename: Mika J
authors.initials: MJ
authors.lastname: Mäkelä
authors.forename: Joan E
authors.initials: JE
authors.lastname: Loader
authors.forename: Gary L
authors.initials: GL
authors.lastname: Larsen
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001980:Bronchi / Q000737:chemistry / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D004558:Electric Stimulation; D004804:Eosinophils / Q000473:pathology; D007114:Immunization; D007150:Immunohistochemistry; D007249:Inflammation; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008168:Lung / Q000737:chemistry / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000485:Allergens; D000906:Antibodies; D039041:Integrin alpha4beta1; D016023:Integrins; D015848:Interleukin-5; D016201:Receptors, Lymphocyte Homing; D010047:Ovalbumin; D015740:Calcitonin Gene-Related Peptide