Santing R E, Olymulder C G, Zaagsma J, Meurs H
Department of Pharmacology and Therapeutics, University Centre for Pharmacy, Groningen, The Netherlands.
J Allergy Clin Immunol. 1994 Jun;93(6):1021-30. doi: 10.1016/s0091-6749(94)70051-6.
The relationship among allergen-induced early asthmatic reactions (EARs) and late asthmatic reactions (LARs), early (between EAR and LAR) and late (after LAR) changes in bronchial reactivity to histamine and infiltration of inflammatory cells into the airways were investigated with a new model of chronically instrumented, unrestrained, and ovalbumin-sensitized guinea pigs. Two different provocation strategies were examined. With the use of stepwise increasing allergen concentrations, all 21 animals responded with an EAR, which in 15 animals (71%) was followed by an LAR. By inhalation of a single allergen concentration for up to 15 minutes, 11 of 14 animals showed an EAR, which in 10 animals (71%) was followed by an LAR. One animal did not respond, whereas the remaining two showed only an LAR. At 6 hours (after the EAR) and 24 hours (after the LAR) after allergen provocation, a significant bronchial hyperreactivity (BHR) toward histamine aerosol was observed in the dual responding animals (both protocols), but not significant changes were observed in animals with a single EAR or a single LAR. Significant correlations were found between the initial increase in airway obstruction after allergen provocation and the severity of the EAR and LAR, as well as the early and late BHR; in addition, a significant correlation was found between the early and late BHR. In contrast, the severity of the LAR did not correlate with the BHR at 6 hours and 24 hours. At 6 hours, there was a marked tendency to an increase in the number of eosinophils and a significant increase in the number of neutrophils in the bronchoalveolar lavage. At 24 hours after provocation, the number of eosinophils and neutrophils was significantly enhanced. These data suggest that early activation of mast cells and/or inflammatory leukocytes may determine the development of the LAR, as well as the early and late BHR, although there appears to be no causal relationship between the BHR at both time points and the severity of the LAR. The relationships among allergen-induced EAR and LAR, early and late BHR, and airway inflammation observed in this new guinea pig model are strikingly similar to those observed in patients with asthma.
采用一种新的长期植入仪器、不受束缚且对卵清蛋白致敏的豚鼠模型，研究了变应原诱导的早期哮喘反应（EARs）与迟发哮喘反应（LARs）之间的关系，以及支气管对组胺反应性的早期（EAR与LAR之间）和晚期（LAR之后）变化，还有炎性细胞向气道的浸润情况。研究了两种不同的激发策略。使用逐步增加变应原浓度的方法，所有21只动物均出现EAR，其中15只动物（71%）随后出现LAR。通过吸入单一变应原浓度长达15分钟，14只动物中的11只出现EAR，其中10只动物（71%）随后出现LAR。1只动物无反应，而其余2只仅出现LAR。在变应原激发后6小时（EAR后）和24小时（LAR后），在双重反应动物（两种方案）中观察到对组胺气雾剂有显著的支气管高反应性（BHR），但在仅有单一EAR或单一LAR的动物中未观察到显著变化。变应原激发后气道阻塞的初始增加与EAR和LAR的严重程度以及早期和晚期BHR之间存在显著相关性；此外，早期和晚期BHR之间也存在显著相关性。相比之下，LAR的严重程度与6小时和24小时时的BHR无关。在6小时时，支气管肺泡灌洗中嗜酸性粒细胞数量有明显增加趋势，中性粒细胞数量显著增加。激发后24小时，嗜酸性粒细胞和中性粒细胞数量显著增加。这些数据表明，肥大细胞和/或炎性白细胞的早期激活可能决定LAR以及早期和晚期BHR的发展，尽管两个时间点的BHR与LAR的严重程度之间似乎没有因果关系。在这个新的豚鼠模型中观察到的变应原诱导的EAR和LAR、早期和晚期BHR以及气道炎症之间的关系与哮喘患者中观察到的关系惊人地相似。
