Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria
Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria
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DOI：
10.1016/j.jaci.2014.05.004
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发表时间：
2014-09-01
影响因子：
14.2
通讯作者：
Okayama, Yoshimichi
中科院分区：
文献类型：
--
作者：
Fujisawa, Daisuke;Kashiwakura, Jun-ichi;Okayama, Yoshimichi
背景：慢性荨麻疹（CU）患者皮内注射神经肽（如P物质（SP）和血管活性肠肽）的呼吸道反应明显大于非特应性对照组（NC）。mas相关基因X2 （MrgX2）被认为是SP和血管活性肠肽等基础神经肽的受体。肥大细胞（MC）对嗜酸性粒细胞介质的反应性有助于过敏的晚期反应。目的：我们试图比较CU和NC患者皮肤MCs中MrgX2的表达频率，并鉴定人皮肤MCs中碱性嗜酸性粒细胞颗粒蛋白的受体。方法：采用免疫荧光法检测NC、重症CU患者皮肤组织及皮肤源性培养MCs中MrgX2的表达。使用慢病毒小发夹RNA沉默技术降低MrgX2在人MCs中的表达。在MrgX2转染的CHO细胞中测量Ca2+内流，以响应嗜酸性粒细胞颗粒蛋白。采用酶免疫法测定组胺和前列腺素D-2水平。结果：CU患者MrgX2（+）皮肤MCs数量及MrgX2(+) MCs占全部MCs的比例均显著高于NC组。9例CU患者中有7例在荨麻疹病变处观察到嗜酸性粒细胞浸润。SP，主要碱性蛋白和嗜酸性粒细胞过氧化物酶，而不是嗜酸性粒细胞来源的神经毒素，通过MrgX2诱导组胺从人皮肤MCs释放。结论：MrgX2可能是治疗重症CU患者车轮反应的新靶点分子。
Background: Wheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a receptor for basic neuropeptides, such as SP and vasoactive intestinal peptide. Mast cell (MC) responsiveness to eosinophil mediators contributes to the late-phase reaction of allergy.Objective: We sought to compare the frequency of MrgX2 expression in skin MCs from patients with CU and NC subjects and to identify the receptor for basic eosinophil granule proteins on human skin MCs.Methods: MrgX2 expression was investigated by using immunofluorescence in skin tissues from NC subjects and patients with severe CU and on skin-derived cultured MCs. MrgX2 expression in human MCs was reduced by using a lentiviral small hairpin RNA silencing technique. Ca2+ influx was measured in CHO cells transfected with MrgX2 in response to eosinophil granule proteins. Histamine and prostaglandin D-2 levels were measured by using enzyme immunoassays.Results: The number of MrgX2(+) skin MCs and the percentage of MrgX2(+) MCs in all MCs in patients with CU were significantly greater than those in NC subjects. Eosinophil infiltration in urticarial lesions was observed in 7 of 9 patients with CU. SP, major basic protein, and eosinophil peroxidase, but not eosinophil-derived neurotoxin, induced histamine release from human skin MCs through MrgX2.Conclusion: MrgX2 might be a new target molecule for the treatment of wheal reactions in patients with severe CU.