Hutson P A, Church M K, Clay T P, Miller P, Holgate S T
Immunopharmacology Group, Southhampton General Hospital, United Kingdom.
Am Rev Respir Dis. 1988 Mar;137(3):548-57. doi: 10.1164/ajrccm/137.3.548.
We describe a guinea pig model of asthma in which animals were sensitized and challenged by inhalation of aerosolized ovalbumin. Challenge was performed under cover of mepyramine (10 mg/kg) to allow a high enough concentration of ovalbumin to elicit consistent late responses. Airway resistance and thoracic gas volume of conscious guinea pigs was assessed by whole body plethysmography before and at regular intervals for as long as 72 h after challenge. At the same time points, cellular changes in the lung were assessed by both examination of cells recovered by bronchoalveolar lavage (BAL) and lung histology. There were no significant changes in specific airway conductance (SGaw), BAL cell content or lung histology in animals challenged with saline control. Challenge with 2% ovalbumin caused an early fall in SGaw, which peaked at 2 h and amounted to a 43.7 +/- 4.1% fall from baseline. This was followed by 2 late responses, the first reaching maximum at 17 h with a 46.9 +/- 4.5% decrease in SGaw from baseline and the second at 72 h with a 39.0 +/- 3.5% fall in SGaw. Examination of BAL fluid revealed a 7-fold increase in neutrophils at 6 h and a 17-fold increase at 17 h, after which numbers decreased to baseline. Eosinophilia developed more slowly, being insignificant at 6 h and 6-fold at 17 h; by 72 h, eosinophils constituted 48.9 +/- 6.9% of the total cells recovered. No changes in mononuclear cells or lymphocytes were observed. Histologic examination of the lung revealed a progressive eosinophil infiltration of the airways, but not alveoli or vascular bed. Electron microscopy showed degranulation of eosinophils recovered by BAL and discharge of mucus from goblet cells in the trachea. Because these changes are similar to those that occur after allergen challenge in human asthma, we suggest that this represents a useful animal model in which to study the mechanism of early and late bronchoconstriction responses.
我们描述了一种哮喘豚鼠模型，其中动物通过吸入雾化卵清蛋白进行致敏和激发。在吡拉明（10mg/kg）的掩护下进行激发，以使足够高浓度的卵清蛋白引发一致的迟发反应。在激发前以及激发后长达72小时的定期时间点，通过全身体积描记法评估清醒豚鼠的气道阻力和胸内气体容积。在同一时间点，通过支气管肺泡灌洗（BAL）回收的细胞检查和肺组织学评估肺中的细胞变化。用盐水对照激发的动物在特定气道传导率（SGaw）、BAL细胞含量或肺组织学方面没有显著变化。用2%卵清蛋白激发导致SGaw早期下降，在2小时达到峰值，相对于基线下降了43.7±4.1%。随后出现2个迟发反应，第一个在17小时达到最大值，SGaw相对于基线下降46.9±4.5%，第二个在72小时，SGaw下降39.0±3.5%。对BAL液的检查显示，中性粒细胞在6小时增加了7倍，在17小时增加了17倍，之后数量降至基线。嗜酸性粒细胞增多发展较慢，在6小时不显著，在17小时为6倍；到72小时，嗜酸性粒细胞占回收的总细胞的48.9±6.9%。未观察到单核细胞或淋巴细胞的变化。肺组织学检查显示气道有进行性嗜酸性粒细胞浸润，但肺泡或血管床没有。电子显微镜显示BAL回收的嗜酸性粒细胞脱颗粒以及气管杯状细胞分泌黏液。因为这些变化与人类哮喘变应原激发后发生的变化相似，我们认为这代表了一种有用的动物模型，可用于研究早期和迟发性支气管收缩反应的机制。
