title: Attenuation of antigen-induced airway hyperresponsiveness in CGRP-deficient mice.
abstract: Bronchial hyperresponsiveness and eosinophilia are major characteristics of asthma. Calcitonin gene-related peptide (CGRP) is a neuropeptide that has various biological actions. In the present study, we questioned whether CGRP might have pathophysiological roles in airway hyperresponsiveness and eosinophilia in asthma. To determine the exact roles of endogenous CGRP in vivo, we chose to study antigen-induced airway responses using CGRP gene-disrupted mice. After ovalbumin sensitization and antigen challenge, we assessed airway responsiveness and measured proinflammatory mediators. In the sensitized CGRP gene-disrupted mice, antigen-induced bronchial hyperresponsiveness was significantly attenuated compared with the sensitized wild-type mice. Antigen challenge induced eosinophil infiltration in bronchoalveolar lavage fluid, whereas no differences were observed between the wild-type and CGRP-mutant mice. Antigen-induced increases in cysteinyl leukotriene production in the lung were significantly reduced in the CGRP-disrupted mice. These findings suggest that CGRP could be involved in the antigen-induced airway hyperresponsiveness, but not eosinophil infiltration, in mice. The CGRP-mutant mice may provide appropriate models to study molecular mechanisms underlying CGRP-related diseases.
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Aoki-Nagase
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Oh-Hashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shindo
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Tomita
authors.forename: Eijiro
authors.initials: E
authors.lastname: Ohga
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurihara
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
mesh_terms: D000818:Animals; D000941:Antigens; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015698:Genomic Library; D005838:Genotype; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology*
chemical_list: D000941:Antigens; D016210:Methacholine Chloride; D010047:Ovalbumin; D004247:DNA; D015740:Calcitonin Gene-Related Peptide