O'Sullivan S, Roquet A, Dahlén B, Dahlén S, Kumlin M
Experimental Asthma & Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Clin Exp Allergy. 1998 Nov;28(11):1332-9. doi: 10.1046/j.1365-2222.1998.00368.x.
It is generally accepted that the early asthmatic response to inhaled allergen is a result of IgE-mediated mast cell activation. In contrast, the underlying mechanism of the late asthmatic response is much less clear.
In order to investigate the pattern of mediator release during the early and late asthmatic responses to allergen, measurements of the urinary excretion of the mast cell markers 9alpha,11beta-PGF2 and Ntau-methylhistamine were made. In addition, urinary levels of eosinophil protein X (EPX) and leukotriene E4 (LTE4) were measured.
Twelve mild atopic asthmatics participated in the study. On the study day, pulmonary function was recorded at baseline and for 12 h after inhalation of allergen. Urine was collected prior to challenge and thereafter at 1 h intervals. Measurements of 9alpha, 11beta-PGF2 and LTE4 were made with enzyme-immunoassay, and levels of Ntau-methylhistamine and EPX were analysed with radioimmunoassay.
All subjects developed both an early and late phase airway response. Within 1 h of the early peak airway response, there was a significant increase in the urinary concentrations (AUC/h) of 9alpha, 11beta-PGF2 (49.3 +/- 9.2 to 142.5 +/- 49.2; P < 0.001) Ntau-methylhistamine (10.4 +/- 1.4 to 19.5 +/- 1.4; P < 0.001) and LTE4 (43.7 +/- 5.9 to 105.9 +/- 21.3; P < 0.001). Levels of all three mediators were also significantly increased above baseline during the LAR to 79.4 +/- 9.5 (P < 0.01), 19.8 +/- 1.9 (P < 0.001) and 85.6 +/- 10.4 (P < 0.001), respectively. Levels of EPX remained unchanged during the early and late responses (39.2 +/- 10.2 to 37.5 +/- 18.5, 33.9 +/- 6.8).
These results indicate that mast cell activation is a feature not only of the early but also the late asthmatic response. Finally, increased LTE4 supports the contribution of the leukotrienes to airway obstruction during both phases of the asthmatic response to allergen.
一般认为，哮喘患者对吸入变应原的早期反应是由IgE介导的肥大细胞活化所致。相比之下，迟发哮喘反应的潜在机制则不太清楚。
为了研究变应原诱发的哮喘早期和晚期反应过程中介质释放的模式，对肥大细胞标志物9α,11β-前列腺素F2（9α,11β-PGF2）和Nτ-甲基组胺的尿排泄量进行了测定。此外，还测定了尿中嗜酸性粒细胞蛋白X（EPX）和白三烯E4（LTE4）的水平。
12名轻度特应性哮喘患者参与了本研究。在研究当天，记录基线时以及吸入变应原后12小时的肺功能。在激发前及之后每隔1小时收集尿液。采用酶免疫法测定9α,11β-PGF2和LTE4，采用放射免疫法分析Nτ-甲基组胺和EPX的水平。
所有受试者均出现了早期和晚期气道反应。在早期气道反应峰值出现后的1小时内，9α,11β-PGF2（49.3±9.2至142.5±49.2；P<0.001）、Nτ-甲基组胺（10.4±1.4至19.5±1.4；P<0.001）和LTE4（43.7±5.9至105.9±21.3；P<0.001）的尿浓度（AUC/h）显著升高。在迟发哮喘反应期间，所有这三种介质的水平也显著高于基线，分别为79.4±9.5（P<0.01）、19.8±1.9（P<0.001）和85.6±10.4（P<0.001）。在早期和晚期反应期间，EPX水平保持不变（39.2±10.2至37.5±18.5，33.9±6.8）。
这些结果表明，肥大细胞活化不仅是哮喘早期反应的特征，也是晚期反应的特征。最后，LTE4升高支持了白三烯在变应原诱发的哮喘反应两个阶段中对气道阻塞的作用。
