Hessel E M, Van Oosterhout A J, Hofstra C L, De Bie J J, Garssen J, Van Loveren H, Verheyen A K, Savelkoul H F, Nijkamp F P
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Netherlands.
Eur J Pharmacol. 1995 Dec 7;293(4):401-12. doi: 10.1016/0926-6917(95)90061-6.
To investigate the mechanisms underlying airway hyperresponsiveness a murine model was developed with several important characteristics of human allergic asthma. Mice were intraperitoneally sensitized with ovalbumin and after 4 weeks challenge via an ovalbumin aerosol. After aerosol, lung function was evaluated with a non-invasive forced oscillation technique. The amount of mucosal exudation into the airway lumen and the presence of mast cell degranulation was determined. Tracheal responsiveness was measured at several time points after challenge. At these time points also bronchoalveolar lavage and histology were performed. Sensitization induced high antigen-specific IgE levels in serum. Inhalation of ovalbumin in sensitized mice induced an immediate but no late bronchoconstrictive response. During this immediate phase, respiratory resistance was increased (54%). Within the first hour after ovalbumin inhalation increased mucosal exudation and mast cell degranulation were observed. At 12 and 24 h after ovalbumin challenge, mice showed tracheal hyperresponsiveness (29% and 34%, respectively). However, no apparent inflammation was found in the lungs or bronchoalveolar lavage. From these results it can be concluded that hyperresponsiveness can develop via mechanisms independent of an inflammatory infiltrate. Since mast cell degranulation occurred after ovalbumin exposure, we hypothesize that mast cells are involved in the induction of airway hyperresponsiveness in this model.
为了研究气道高反应性的潜在机制，构建了一种具有人类过敏性哮喘若干重要特征的小鼠模型。用卵清蛋白对小鼠进行腹腔致敏，4周后通过卵清蛋白气雾剂进行激发。气雾剂激发后，采用无创强迫振荡技术评估肺功能。测定气道腔内粘膜渗出量和肥大细胞脱颗粒情况。在激发后的几个时间点测量气管反应性。在这些时间点还进行支气管肺泡灌洗和组织学检查。致敏诱导血清中高抗原特异性IgE水平。在致敏小鼠中吸入卵清蛋白诱导即刻但无迟发性支气管收缩反应。在这个即刻阶段，呼吸阻力增加（54%）。在吸入卵清蛋白后的第一小时内，观察到粘膜渗出增加和肥大细胞脱颗粒。在卵清蛋白激发后12小时和24小时，小鼠出现气管高反应性（分别为29%和34%）。然而，在肺或支气管肺泡灌洗中未发现明显炎症。从这些结果可以得出结论，高反应性可通过独立于炎症浸润的机制发展。由于在暴露于卵清蛋白后发生了肥大细胞脱颗粒，我们推测肥大细胞参与了该模型中气道高反应性的诱导。
