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This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 102/6/2361    most recent 00615.2006v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Yamamoto, H. Articles by Ouchi, Y. Search for Related Content PubMed PubMed Citation Articles by Yamamoto, H. Articles by Ouchi, Y.

Adrenomedullin insufficiency increases allergen-induced airway hyperresponsiveness in mice

Departments of ¹Geriatric Medicine, ²Respiratory Medicine, and ⁴Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, Tokyo; and ³Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Nagano, Japan

Submitted 2 June 2006 ; accepted in final form 25 February 2007

Adrenomedullin (ADM), a newly identified vasodilating peptide, is reported to be expressed in lungs and have a bronchodilating effect. We hypothesized whether ADM could be involved in the pathogenesis of bronchial asthma. We examined the role of ADM in airway responsiveness using heterozygous ADM-deficient mice (AM^+/–) and their littermate control (AM^+/+). Here, we show that airway responsiveness is enhanced in ADM mutant mice after sensitization and challenge with ovalbumin (OVA). The immunoreactive ADM level in the lung tissue after methacholine challenge was significantly greater in the wild-type mice than that in the mutant. However, the impairment of ADM gene function did not affect immunoglobulins (OVA-specific IgE and IgG1), T helper 1 and 2 cytokines, and leukotrenes. Thus the conventional mechanism of allergen-induced airway responsiveness is not relevant to this model. Furthermore, morphometric analysis revealed that eosinophilia and airway hypersecretion were similarly found in both the OVA-treated ADM mutant mice and the OVA-treated wild-type mice. On the other hand, the area of the airway smooth muscle layer of the OVA-treated mutant mice was significantly greater than that of the OVA-treated wild-type mice. These results suggest that ADM gene disruption may be associated with airway smooth muscle hyperplasia as well as enhanced airway hyperresponsiveness. ADM mutant mice might provide novel insights to study the pathophysiological role of ADM in vivo.

asthma; airway hyperresponsiveness; remodeling; adrenomedullin; knockout mouse