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Am J Physiol Lung Cell Mol Physiol 283: L963-L970, 2002. First published June 21, 2002; doi:10.1152/ajplung.00130.2002
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Vol. 283, Issue 5, L963-L970, November 2002

Attenuation of antigen-induced airway hyperresponsiveness in CGRP-deficient mice

Tomoko Aoki-Nagase1, Takahide Nagase1, Yoshio Oh-Hashi2, Takayuki Shindo2, Yukiko Kurihara2, Yasuhiro Yamaguchi1, Hiroshi Yamamoto1, Tetsuji Tomita1, Eijiro Ohga1, Ryozo Nagai2, Hiroki Kurihara3, and Yasuyoshi Ouchi1

1 Departments of Geriatric Medicine and 2 Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655; and 3 Division of Integrative Cell Biology, Department of Embryogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 862-0976, Japan

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.

asthma; bronchial hyperreactivity; eosinophilia; leukotriene; knockout mouse


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