Attenuation of antigen-induced airway hyperresponsiveness in CGRP-deficient mice.
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.
Aoki-Nagase
Tomoko
T
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Nagase
Takahide
T
Oh-Hashi
Yoshio
Y
Shindo
Takayuki
T
Kurihara
Yukiko
Y
Yamaguchi
Yasuhiro
Y
Yamamoto
Hiroshi
H
Tomita
Tetsuji
T
Ohga
Eijiro
E
Nagai
Ryozo
R
Kurihara
Hiroki
H
Ouchi
Yasuyoshi
Y
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*
D000941:Antigens; D016210:Methacholine Chloride; D010047:Ovalbumin; D004247:DNA; D015740:Calcitonin Gene-Related Peptide