Key result
AT1a knockout mice exhibited significantly higher levels of OVA-specific IgE, eosinophils, and Th2 cytokines in BAL fluid compared to wild-type mice after OVA inhalation.
Why the study?
Does genetic deletion of AT1a receptors exacerbate allergic airway inflammation in a murine model of asthma?
Does genetic deletion of AT1a receptors exacerbate allergic airway inflammation in a murine model of asthma?
Type 1a angiotensin II receptors may negatively regulate allergic airway inflammation by promoting a Th1-predominant response, suggesting potential implications for the use of AT1 blockers in asthmatic patients.
AT1a deletion exacerbates allergic airway inflammation in mice; leaves open whether AT1 blockade affects human asthma.
BACKGROUND: There has been increasing evidence suggesting the involvement of angiotensin II (Ang II) and type 1 Ang II receptors (AT1) in the pathogenesis of bronchial asthma. However, whether such an involvement would promote or suppress the pathophysiology of asthma is controversial. OBJECTIVE: The aim of this study was to investigate the role of AT1 in the development of allergic airway inflammation. METHODS: Agtr1a+/+ [wild-type C57BL/6 mice (WT)] and Agtr1a-/- mice [AT1a knockout mice (AT1aKO)] with a genetic background of C57BL/6 were systemically sensitized to ovalbumin (OVA), followed by OVA inhalation. OVA-specific IgE in serum obtained just before the inhalation was measured. Bronchoalveolar lavage (BAL) fluid and lung tissues were obtained at various time-points. Cell numbers and differentiation, and cytokine contents in BAL fluids were determined. Peribronchial accumulation of eosinophils and mucus inclusions in the bronchial epithelium were evaluated in lung tissues stained histochemically. Cell numbers and differentiation in BAL fluids of the mice were also determined after lipopolysaccharide (LPS) inhalation. RESULTS: The levels of OVA-specific IgE in AT1aKO were significantly higher than those in WT. The numbers of total cell, eosinophils and lymphocytes in BAL fluids 7 days after OVA inhalation in AT1aKO were significantly higher than those in WT. Airway inflammation in bronchial tissues in terms of eosinophil accumulation and mucus hypersecretion in AT1aKO was also stronger than in WT. The contents of IL-4, IL-5 and IL-13, but not IFN-gamma, in BAL fluids of AT1aKO were significantly higher than those of WT. In contrast, neutrophil accumulation in BAL fluids after LPS inhalation was significantly higher in WT than in AT1aKO. CONCLUSION: AT1a might be involved in the negative regulation of the development of allergic airway inflammation through polarizing the T-helper (Th) balance towards Th1 predominance. Therefore, it would be of clinical importance to investigate the effects of long-term administration of AT1 blockers on the Th1/Th2 balance in hypertensive patients with bronchial asthma.
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Ohwada et al. (2007) studied Allergic asthma (murine model). AT1a knockout (Agtr1a-/-) vs. Wild-type (Agtr1a+/+) was evaluated on OVA-specific IgE levels, cell numbers in BAL fluid, and airway inflammation. AT1a knockout mice exhibited significantly higher levels of OVA-specific IgE, eosinophils, and Th2 cytokines in BAL fluid compared to wild-type mice after OVA inhalation.
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