Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
Immunology. 2013 Dec;140(4):465-74. doi: 10.1111/imm.12157.
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 mFcεRI α-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 hFcεRI α-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.
过敏疾病常在午夜至清晨时分加剧，提示生物节律可能起作用。肥大细胞（MC）和嗜酸性粒细胞是过敏疾病的主要效应细胞，一些 MC 特异性或嗜酸性粒细胞特异性标志物，如类胰蛋白酶或嗜酸性粒细胞阳离子蛋白，表现出昼夜节律变化。在这里，我们分析了生物钟是否在小鼠和人类嗜酸性粒细胞和 MC 中起作用。围绕昼夜节律周期，从小鼠空肠 MC 和外周血多形核细胞（PMNC）中分离细胞。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 mPer1、mPer2、mClock 和 mBmal1 以及嗜酸性粒细胞特异性基因 mEcp、mEpo 和 mMbp 呈节律性表达。我们还发现健康和过敏人群的人嗜酸性粒细胞中 hPer1、hPer2、hBmal1、hClock、hEdn 和 hEcp mRNA 以及嗜酸性粒细胞阳离子蛋白（ECP）存在昼夜节律变化。时钟基因 mPer1、mPer2、mClock 和 mBmal1 以及 MC 特异性基因 mMcpt-5、mMcpt-7、mc-kit 和 mFcεRI α 链和 mMCPT5 和 mc-Kit 蛋白水平在小鼠空肠中表现出强烈的振荡。人肠 MC 以昼夜节律方式表达 hPer1、hPer2 和 hBmal1 以及 h 类胰蛋白酶和 hFcεRI α 链。我们发现，MC 在 IgE 介导的激活后，以昼夜节律的方式释放预先储存的组胺和新合成的半胱氨酰白三烯。总之，生物钟控制 MC 和嗜酸性粒细胞，导致其介质呈昼夜节律表达和释放，因此可能参与过敏的病理生理学。
