Gradual increase in priming of human eosinophils during extravasation from peripheral blood to the airways in response to allergen challenge
Gradual increase in priming of human eosinophils during extravasation from peripheral blood to the airways in response to allergen challenge
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DOI：
10.1016/j.jaci.2005.02.002
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发表时间：
2005-05-01
影响因子：
14.2
通讯作者：
Koenderman, L
中科院分区：
文献类型：
--
作者：
Luijk, B;Lindemans, CA;Koenderman, L
背景：与正常对照细胞相比，从过敏性哮喘患者血液中分离的嗜酸性粒细胞对多种刺激的反应性增强，这种现象通常称为启动。这种启动反应对于增强反应的最佳激活至关重要，包括趋化性、细胞毒性、呼吸爆发和促炎脂质介质的释放。目的：监测变应原激发前后过敏性哮喘患者外周血和支气管肺泡灌洗液中嗜酸性粒细胞的引发动力学。方法：通过识别吞噬细胞上引发相关表位的单克隆噬菌体抗体 A17 和 A27 标记，测量从过敏患者和非过敏供者获得的血液嗜酸性粒细胞的引发。此外，对部分和全肺过敏原激发后过敏受试者的血液和支气管肺泡灌洗液嗜酸性粒细胞进行了类似分析。结果：发现了剂量依赖性细胞因子诱导的血液嗜酸性粒细胞上启动相关表位的上调。过敏性哮喘患者表现出体内部分引发的嗜酸性粒细胞表型，在细胞因子或趋化因子孵育后在体外进一步引发。全肺攻击后以及分段过敏原攻击后6小时，外周血中的引发增加。有趣的是，节段性过敏原激发后48小时从支气管肺泡灌洗液中获得的嗜酸性粒细胞表现出更高的引发表型。结论：这些数据与局部过敏性炎症反应诱导外周血中部分全身性嗜酸性粒细胞引发的模型一致。气道中发现的嗜酸性粒细胞高度引发，与在这些细胞中观察到的明显上调的炎症能力一致。
Background: Eosinophils isolated from the blood of patients with allergic asthma exhibit enhanced responsiveness to multiple stimuli compared with cells from normal controls, a phenomenon generally referred to as priming. This priming response is essential for optimal activation with augmented responses including chemotaxis, cytotoxicity, respiratory burst, and the release of proinflammatory lipid mediators. Objective: To monitor the kinetics of priming of eosinophils in the peripheral blood and in the bronchoalveolar lavage fluid of patients with allergic asthma before and after allergen challenge.Methods: Priming of blood eosinophils obtained from patients with allergy and donors without allergy was measured by labeling with monoclonal phage antibodies A17 and A27 recognizing priming-associated epitopes on phagocytes. In addition, blood and bronchoalveolar lavage fluid eosinophils from subjects with allergy after segmental and whole lung allergen challenge were similarly analyzed.Results: A dose-dependent cytokine-induced upregulation of priming-associated epitopes on blood eosinophils was found. Patients with allergic asthma exhibited an in vivo partially primed eosinophil phenotype, which is further primed in vitro after cytokine or chemokine incubation. Priming was increased in peripheral blood 6 hours after whole lung challenge as well as after segmental allergen challenge. Interestingly, eosinophils obtained from the bronchoalveolar lavage fluid 48 hours after segmental allergen challenge exhibited a higher primed phenotype.Conclusion: These data are consistent with a model in which local allergic inflammatory reactions induce partial systemic eosinophil priming in the peripheral blood. Eosinophils found in the airway are highly primed, consistent with the markedly upregulated inflammatory capacity observed in these cells.