哮喘患者IgE结合后嗜碱性粒细胞脱颗粒反应由独特的昼夜节律钟所控制
2019/08/27
摘要
背景：哮喘和过敏临床表现的昼夜变化可能与某些因素有关。嗜碱性粒细胞在过敏性炎症中起着关键作用。然而，控制这些细胞效应器功能的生物钟的证据是稀缺和矛盾的。我们对哮喘患者嗜碱性粒细胞对IgE依赖和非IgE依赖配体的24小时反应性进行了系统抽样，以了解它们可能对过敏症状每日变化的影响。
方法：对10例中度、持续性哮喘患者和10例配对、非过敏性对照者，每4小时采集24小时内的白细胞，分别用抗IgE、甲酰甲氧基亮氨酸（fMLP）或Ca2+离子载体、A23187培养。组胺释放量（HR）通过常规统计方法检测时间相关或疾病相关变异性，并通过余弦法检测24小时节律性。
结果：哮喘嗜碱性粒细胞在08:00和20:00时，抗IgE诱导的HR显著升高，而对照组则无显著性差异。对A23187的反应在任何时间都没有显著差异；相比哮喘组，对照组对fMLP的反应08:00比20:00明显更高。嗜碱性粒细胞对抗IgE的反应，在哮喘24小时内显著变化，其振幅、百分比节律和峰值期与呼气峰流量或血清皮质醇的峰值相似，但fMLP或A23187并没有。
结论：采用综合统计方法，我们发现嗜碱性粒细胞的反应经历了显著的昼夜变化，并且根据信号的传递、评估活化参数和疾病状态，可识别出不同的节律模式。
Basophil degranulation in response to IgE ligation is controlled by a distinctive circadian clock in asthma.
Spadaro G, Giurato G, Stellato C, Marone G, Casolaro V.
Abstract
BACKGROUND: Several factors may contribute to the circadian variability of clinical manifestations in asthma and allergy. Basophils play a pivotal role in allergic inflammation. However, evidence for a functional clock governing the effector function of these cells is sparse and contradictory. We have systematically sampled the 24-hour response of basophils to IgE- and non-IgE-dependent ligands in asthma to understand their possible contribution to the diurnal variations of allergic symptoms.
METHODS: Leukocytes were collected every 4 hours for 24 hours from 10 patients with moderate, persistent asthma and 10 matched, non-allergic controls, then incubated with concentrations of anti-IgE, formyl-methionyl-leucylphenylalanine (fMLP), or the Ca2+ ionophore, A23187. Histamine release (HR) was tested for time-of-day- or disease-related variability by conventional statistics and for 24-hour rhythmicity by the cosinor method.
RESULTS: HR induced by anti-IgE was significantly increased at 08:00 vs. 20:00 in basophils from asthmatics but not controls. No significant differences were seen at any time in the response to A23187, while the response to fMLP was significantly higher at 08:00 vs. 20:00 in controls but not asthmatics. The basophil response to anti-IgE, but not fMLP or A23187, varied significantly across the 24 hours in asthma, and its amplitude, percent rhythm and acrophase were comparable to those of peak expiratory flow or serum cortisol.
CONCLUSION: Using an integrated statistical approach we show that basophil responsiveness undergoes significant circadian variability, and that distinct patterns of rhythmicity can be recognized depending on the signal delivered, the activation parameters assessed, and the disease status. This article is protected by copyright. All rights reserved.
背景：哮喘和过敏临床表现的昼夜变化可能与某些因素有关。嗜碱性粒细胞在过敏性炎症中起着关键作用。然而，控制这些细胞效应器功能的生物钟的证据是稀缺和矛盾的。我们对哮喘患者嗜碱性粒细胞对IgE依赖和非IgE依赖配体的24小时反应性进行了系统抽样，以了解它们可能对过敏症状每日变化的影响。
方法：对10例中度、持续性哮喘患者和10例配对、非过敏性对照者，每4小时采集24小时内的白细胞，分别用抗IgE、甲酰甲氧基亮氨酸（fMLP）或Ca2+离子载体、A23187培养。组胺释放量（HR）通过常规统计方法检测时间相关或疾病相关变异性，并通过余弦法检测24小时节律性。
结果：哮喘嗜碱性粒细胞在08:00和20:00时，抗IgE诱导的HR显著升高，而对照组则无显著性差异。对A23187的反应在任何时间都没有显著差异；相比哮喘组，对照组对fMLP的反应08:00比20:00明显更高。嗜碱性粒细胞对抗IgE的反应，在哮喘24小时内显著变化，其振幅、百分比节律和峰值期与呼气峰流量或血清皮质醇的峰值相似，但fMLP或A23187并没有。
结论：采用综合统计方法，我们发现嗜碱性粒细胞的反应经历了显著的昼夜变化，并且根据信号的传递、评估活化参数和疾病状态，可识别出不同的节律模式。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Allergy. 2019 Jul 29. doi: 10.1111/all.14002. )
(Allergy. 2019 Jul 29. doi: 10.1111/all.14002. )
Basophil degranulation in response to IgE ligation is controlled by a distinctive circadian clock in asthma.
Spadaro G, Giurato G, Stellato C, Marone G, Casolaro V.
Abstract
BACKGROUND: Several factors may contribute to the circadian variability of clinical manifestations in asthma and allergy. Basophils play a pivotal role in allergic inflammation. However, evidence for a functional clock governing the effector function of these cells is sparse and contradictory. We have systematically sampled the 24-hour response of basophils to IgE- and non-IgE-dependent ligands in asthma to understand their possible contribution to the diurnal variations of allergic symptoms.
METHODS: Leukocytes were collected every 4 hours for 24 hours from 10 patients with moderate, persistent asthma and 10 matched, non-allergic controls, then incubated with concentrations of anti-IgE, formyl-methionyl-leucylphenylalanine (fMLP), or the Ca2+ ionophore, A23187. Histamine release (HR) was tested for time-of-day- or disease-related variability by conventional statistics and for 24-hour rhythmicity by the cosinor method.
RESULTS: HR induced by anti-IgE was significantly increased at 08:00 vs. 20:00 in basophils from asthmatics but not controls. No significant differences were seen at any time in the response to A23187, while the response to fMLP was significantly higher at 08:00 vs. 20:00 in controls but not asthmatics. The basophil response to anti-IgE, but not fMLP or A23187, varied significantly across the 24 hours in asthma, and its amplitude, percent rhythm and acrophase were comparable to those of peak expiratory flow or serum cortisol.
CONCLUSION: Using an integrated statistical approach we show that basophil responsiveness undergoes significant circadian variability, and that distinct patterns of rhythmicity can be recognized depending on the signal delivered, the activation parameters assessed, and the disease status. This article is protected by copyright. All rights reserved.
上一篇：
在重症哮喘患者中，嗜酸性粒细胞外网状陷阱通过刺激气道上皮活化2型固有淋巴细胞
下一篇：
儿童期和成人期哮喘的遗传结构区别
