Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Massachusetts, USA.
Am J Pathol. 2012 Sep;181(3):845-57. doi: 10.1016/j.ajpath.2012.05.020. Epub 2012 Jul 13.
Asthma may be triggered by multiple mediators, including allergen-IgE cross-linking and non-IgE mechanisms. Several clinical studies have shown acute ethanol consumption exacerbates asthma, yet no animal model exists to study this process. We developed a model of ethanol-triggered asthma in allergen-sensitized mice to evaluate the mechanisms of ethanol inducing asthma-like responses. Outbred mice were exposed to cockroach allergens on Days 0 and 14; and on Day 21, mice received ethanol by oral gavage. Tracer studies confirmed alcohol aspiration did not occur. Within 30 minutes, alcohol induced degranulation of over 74% of mast cells, and multiple parameters of asthma-like pulmonary inflammation were triggered. Ethanol-gavaged mice had a fivefold increased production of eotaxin-2 (534 pg/mL) and a sevenfold increase in bronchoalveolar eosinophils (70,080 cells). Ethanol induced a 10-fold increase in IL-13, from 84 pg/mL in sensitized mice to 845 pg/mL in ethanol-gavaged sensitized mice. In cockroach allergen-sensitized mice, ethanol triggered asthma-like changes in respiratory physiology and a significant fivefold increase in airway mucin production. Importantly, none of these asthmatic exacerbations were observed in normal mice gavaged with ethanol. Cromolyn sodium effectively stabilized mast cells, yet increased mucin production and bronchoalveolar eosinophil recruitment. Together, these data show a single oral alcohol exposure will trigger asthma-like pulmonary inflammation in allergen-sensitized mice, providing a novel asthma model.
哮喘可能由多种介质引发，包括过敏原-IgE 交联和非 IgE 机制。几项临床研究表明，急性乙醇消耗会加重哮喘，但目前尚不存在研究该过程的动物模型。我们开发了一种过敏原致敏小鼠的乙醇诱发哮喘模型，以评估乙醇诱导哮喘样反应的机制。杂合小鼠在第 0 天和第 14 天暴露于蟑螂过敏原；第 21 天，通过口服灌胃给予小鼠乙醇。示踪研究证实没有发生酒精吸入。在 30 分钟内，酒精诱导超过 74%的肥大细胞脱颗粒，并且引发了多种哮喘样肺部炎症参数。乙醇灌胃的小鼠产生的 eotaxin-2（534pg/mL）增加了五倍，肺泡灌洗液中的嗜酸性粒细胞增加了七倍（70,080 个细胞）。乙醇诱导 IL-13 增加了 10 倍，从致敏小鼠中的 84pg/mL 增加到乙醇灌胃致敏小鼠中的 845pg/mL。在蟑螂过敏原致敏的小鼠中，乙醇引发了呼吸生理的哮喘样变化，并导致气道粘蛋白产生显著增加五倍。重要的是，在给予乙醇的正常小鼠中没有观察到这些哮喘加重。色甘酸钠有效地稳定了肥大细胞，但增加了粘蛋白的产生和肺泡灌洗液中的嗜酸性粒细胞募集。总之，这些数据表明单次口服酒精暴露会在过敏原致敏的小鼠中引发哮喘样肺部炎症，为哮喘模型提供了新的研究方向。
