Nabe T, Shinoda N, Yamashita K, Yamamura H, Kohno S
Dept of Pharmacology, Kyoto Pharmaceutical University, Japan.
Eur Respir J. 1998 Mar;11(3):636-42.
Recently, we reported a reproducible model of asthma in guinea-pigs in vivo, which developed a late asthmatic response (LAR) as well as an early response. In this study, time-related changes in the occurrence of the LAR and leucocyte kinesis were assessed. Furthermore, the state of the activation of eosinophils that migrated into the lower airways was characterized in vitro. Guinea-pigs were alternately sensitized/challenged by inhalation with aerosolized ovalbumin adsorbed on aluminium hydroxide and ovalbumin alone, once every 2 weeks. At defined times before and after the fifth challenge, airway resistance was measured, blood was drawn and bronchoalveolar lavage (BAL) and nasal cavity lavage (NCL) were performed. Superoxide anion (.O2-) production of eosinophils was measured with cytochrome c. Occurrence of LAR and considerable increases in circulating eosinophils coincided with each other 5-7 h after the challenge. After 7 h, eosinophil infiltrations into bronchoalveolar spaces were observed. The capacity of eosinophils from the sensitized animals to produce .O2- was higher than those from the non-sensitized ones, when eosinophils were stimulated by platelet-activating factor. Although an increased number of eosinophils in the NCL fluid was observed, it was much less than that in the BAL fluid. Thus, it has been concluded that eosinophilia in the blood and the lung may participate in the occurrence of the late asthmatic response, which is thought to be preferentially evoked in the lower airways in guinea-pigs in vivo.
最近，我们报道了一种可重复的豚鼠体内哮喘模型，该模型出现了迟发性哮喘反应（LAR）以及早期反应。在本研究中，评估了LAR发生的时间相关变化和白细胞动力学。此外，还在体外对迁移至下呼吸道的嗜酸性粒细胞的活化状态进行了表征。豚鼠每隔2周通过吸入吸附在氢氧化铝上的雾化卵清蛋白和单独的卵清蛋白交替进行致敏/激发。在第五次激发前后的特定时间，测量气道阻力、采血，并进行支气管肺泡灌洗（BAL）和鼻腔灌洗（NCL）。用细胞色素c测量嗜酸性粒细胞的超氧阴离子（.O2-）生成量。激发后5-7小时，LAR的出现与循环嗜酸性粒细胞的显著增加同时发生。7小时后，观察到嗜酸性粒细胞浸润至支气管肺泡间隙。当嗜酸性粒细胞受到血小板活化因子刺激时，致敏动物的嗜酸性粒细胞产生.O2-的能力高于未致敏动物。尽管在NCL液中观察到嗜酸性粒细胞数量增加，但其数量远少于BAL液中的数量。因此，得出结论，血液和肺中的嗜酸性粒细胞增多可能参与迟发性哮喘反应的发生，迟发性哮喘反应被认为在豚鼠体内的下呼吸道中优先诱发。
