アレルギー性喘息マウスモデルにおける1型アンジオテンシンII受容体拮抗薬による抗原誘発性気道炎症の抑制

概要

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Chronic airway inflammation and airway hyperresponsiveness (AHR) are prominent features leading to airway narrowing in bronchial asthma. Airway inflammation in asthma is characterized with the accumulation and activation of inflammatory cells such as eosinophils and mast cells, which is orchestrated by a network of Th2 cytokines released mainly from CD4+ T lymphocytes. The peptide hormone angiotensin II (AT II) plays an important role in the regulation of arterial blood pressure. Recently, plasma levels of AT II were reported to be elevated during acute exacerbation of asthma and to be involved in AHR in asthma. However, the pathogenic role of AT II in asthmatic airway inflammation is not fully understood. Here we demonstrated the inhibitory effect of type 1 AT II receptor antagonism on allergen-induced airway inflammation using a murine model of allergic asthma. A type 1 AT II receptor antagonist, TA606, consecutively administered for three days after allergen exposure significantly reduced the numbers of total cells and lymphocytes, but not eosinophils, in bronchoalveolar lavage fluid (BALF) which were increased in BALF of mice exposed to allergen. In contrast, the antagonist did not alter white blood cell counts in the circulation. These data suggest that AT II participates in the induction of airway inflammation through binding to type 1 AT II receptors in asthma.