The circadian clock is functional in eosinophils and mast cells
The circadian clock is functional in eosinophils and mast cells
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DOI：
10.1111/imm.12157
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发表时间：
2013-12-01
期刊：
影响因子：
6.4
通讯作者：
Lorentz, Axel
中科院分区：
文献类型：
--
作者：
Baumann, Anja;Goennenwein, Simone;Lorentz, Axel
过敏性疾病通常在午夜和清晨之间加剧，这表明生物钟的作用。肥大细胞（MC）和嗜酸性粒细胞是变态反应性疾病的主要效应细胞，MC特异性或嗜酸性粒细胞特异性标志物如类胰蛋白酶、嗜酸性粒细胞阳离子蛋白等具有昼夜节律性。在这里，我们分析了昼夜节律钟是否在小鼠和人类嗜酸性粒细胞和MC中发挥作用。在昼夜节律周期周围分离小鼠空肠MC和外周血多形核细胞（PMNC）。从非过敏和过敏受试者的外周血中纯化人嗜酸性粒细胞。从肠组织中纯化人MC。我们发现小鼠PMNC中时钟基因mPer 1、mPer 2、mClock和mBmal 1以及嗜酸性粒细胞特异性基因mEcp、mEpo和mMbp的节律性表达。我们还发现，昼夜变化的hPer 1，hPer 2，hBmal 1，hClock，hEdn和hEcp mRNA和嗜酸性粒细胞阳离子蛋白（ECP）在人类嗜酸性粒细胞的健康和过敏的人。时钟基因mPer 1、mPer 2、mClock和mBmal 1以及MC特异性基因mMcpt-5、mMcpt-7、mc-kit和mFc β RI -链以及mMCPT 5和mc-Kit的蛋白质水平在小鼠空肠中显示出稳健的振荡。人肠道MC表达hPer 1、hPer 2和hBmal 1以及hTryptase和hFc β RI -链，呈昼夜节律。我们发现，预先储存的组胺和从头合成的半胱氨酰白三烯，释放在一个昼夜节律的方式由MC后IgE介导的激活。总之，生物钟控制MC和嗜酸性粒细胞，导致其介质的昼夜表达和释放，因此它可能参与变态反应的病理生理学。
Allergic diseases are frequently exacerbated between midnight and early morning, suggesting a role for the biological clock. Mast cells (MC) and eosinophils are the main effector cells of allergic diseases and some MC-specific or eosinophil-specific markers, such as tryptase or eosinophil cationic protein, exhibit circadian variation. Here, we analysed whether the circadian clock is functional in mouse and human eosinophils and MC. Mouse jejunal MC and polymorphonuclear cells from peripheral blood (PMNC) were isolated around the circadian cycle. Human eosinophils were purified from peripheral blood of non-allergic and allergic subjects. Human MC were purified from intestinal tissue. We found a rhythmic expression of the clock genes mPer1, mPer2, mClock and mBmal1 and eosinophil-specific genes mEcp, mEpo and mMbp in murine PMNC. We also found circadian variations for hPer1, hPer2, hBmal1, hClock, hEdn and hEcp mRNA and eosinophil cationic protein (ECP) in human eosinophils of both healthy and allergic people. Clock genes mPer1, mPer2, mClock and mBmal1 and MC-specific genes mMcpt-5, mMcpt-7, mc-kit and mFc epsilon RI -chain and protein levels of mMCPT5 and mc-Kit showed robust oscillation in mouse jejunum. Human intestinal MC expressed hPer1, hPer2 and hBmal1 as well as hTryptase and hFc epsilon RI -chain, in a circadian manner. We found that pre-stored histamine and de novo synthesized cysteinyl leukotrienes, were released in a circadian manner by MC following IgE-mediated activation. In summary, the biological clock controls MC and eosinophils leading to circadian expression and release of their mediators and, hence it might be involved in the pathophysiology of allergy.