Gundel R H, Gerritsen M E, Wegner C D
Department of Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.
Am Rev Respir Dis. 1989 Sep;140(3):629-33. doi: 10.1164/ajrccm/140.3.629.
A method of inducing sustained airway eosinophilia and airway hyperresponsiveness in primates has been developed. Our method utilizes a series of intratracheal instillations of Ascaris suum-coated sepharose 4B beads (3 x 10(5] administered once a week for four weeks. Five cynomolgus monkeys (Macaca fascicularis) demonstrating a naturally occurring skin and respiratory sensitivity to Ascaris suum extract were studied. Airway cell composition was measured by bronchoalveolar lavage (BAL), and airway responsiveness was determined as the bronchoconstrictor response to inhaled methacholine. Ascaris suum bead administration resulted in a transient increase in total cells recovered by BAL (2.4 +/- 0.4 to 8.7 +/- 2.5 x 10(5) cells/ml, p less than 0.05) and a selective increase in BAL eosinophils (17 +/- 6 to 916 +/- 158 x 10(3) cells/ml, p less than 0.05). Increases in airway responsiveness were concurrent with the increase in airway eosinophils. These observations show that airway eosinophilia is associated with airway hyperresponsiveness in primates. Furthermore, this new model is a novel experimental system in which the underlying mechanisms in the pathogenesis of airway hyperresponsiveness can be investigated.
已开发出一种在灵长类动物中诱导持续性气道嗜酸性粒细胞增多和气道高反应性的方法。我们的方法利用一系列气管内滴注猪蛔虫包被的琼脂糖4B珠(每周一次给予3×10⁵个,共四周)。对五只对猪蛔虫提取物表现出天然皮肤和呼吸道敏感性的食蟹猴(猕猴)进行了研究。通过支气管肺泡灌洗(BAL)测量气道细胞组成,并将气道反应性确定为对吸入乙酰甲胆碱的支气管收缩反应。给予猪蛔虫珠导致BAL回收的总细胞数短暂增加(从2.4±0.4至8.7±2.5×10⁵个细胞/毫升,p<0.05),且BAL嗜酸性粒细胞选择性增加(从17±6至916±158×10³个细胞/毫升,p<0.05)。气道反应性的增加与气道嗜酸性粒细胞的增加同时发生。这些观察结果表明,气道嗜酸性粒细胞增多与灵长类动物的气道高反应性相关。此外,这个新模型是一种新颖的实验系统,可用于研究气道高反应性发病机制的潜在机制。