Pathophysiological role of Adrenomedullin on the etiology of bronchial asthma and pulmonary fibrosis

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16590737
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: YAMAMOTO Hiroshi The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (10361487)
• Co-Investigator(Kenkyū-buntansha): NAGASE Takahide The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (40208004) ; SHINDO Takayuki Shinshu University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (90345215)
• Project Period (FY): 2004 – 2005
• Keywords: bronchial asthma / pulmonary fibrosis / adrenomedullin

Research Abstract

Heterozygous Adrenomedullin (AM) gene deficient (AMKO) mice and their litter mate control (Wild type) were applied for this study. OVA-induced murine asthma model mice were introduced ; hence they showed greater responsiveness to Methacholine (MCh) inhalation challenge than the wild type (EC200RL : saline-treated AM^<+/+>, 16.81 ± 2.01mg/ml ; saline-treated AM^<+/->, 16.73± 2.34mg/ml ; OVA-treated AM^<+/+>, 7.95 ± 0.98mg/ml ; OVA-treated AM^<+/->, 2.41 ± 0.63^*mg/ml, respectively, ^*P<0.05 vs. the other groups). Immunoreactive AM in the lung tissue of AMKO mice before and after MCh challenge was significantly lower than the wild type. Tissue AM insufficiency might affect enhance airway responsiveness Morphometrical analysis of the sampled lung tissue sections revealed significant airway narrowing, owing to the trophic change of airway smooth muscle cells and/or the swelling of airway epithelial cells. Peribronchial infiltration by eosinophils, airway hypersecretion or goblet cell hyperplasia, TH1, Th2 cytokines, leukotrienes were assessed, but no significant difference between AMKO mice and wild type mice.