肥大细胞非IgE途径活化新型受体mas相关G蛋白偶联受体X2的研究进展

doi:10.3760/cma.j.issn.0412-4030.2019.02.021

中华皮肤科杂志 ›› 2019, Vol. 52 ›› Issue (2): 142-144.doi: 10.3760/cma.j.issn.0412-4030.2019.02.021

肥大细胞非IgE途径活化新型受体mas相关G蛋白偶联受体X2的研究进展

陈安薇白晓明王华

重庆医科大学附属儿童医院皮肤科儿童发育疾病研究教育部重点实验室儿童发育重大疾病国家国际科技合作基地儿科学重庆市重点实验室 400014

收稿日期:2018-01-23 修回日期:2018-05-17 出版日期:2019-02-15 发布日期:2019-01-29
通讯作者: 王华 E-mail:huawang63@hotmail.com
基金资助:
国家自然科学基金（81703124）

Mas-related G protein-coupled receptor X2: a novel receptor for non-IgE-dependent activation of mast cells

Chen Anwei, Bai Xiaoming, Wang Hua

Department of Dermatology, Children′s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China

Received:2018-01-23 Revised:2018-05-17 Online:2019-02-15 Published:2019-01-29
Contact: Wang Hua E-mail:huawang63@hotmail.com
Supported by:
National Natural Science Foundation of China （8170120529）

摘要/Abstract

摘要： 【摘要】肥大细胞（MC）是炎症及变态反应的主要参与者，启动了早期对外来侵袭物的防御反应。除了表达高亲和力IgE受体外，肥大细胞膜表面还表达大量的G蛋白偶联受体（GPCRs）。多项研究表明，P物质为代表的阳离子小分子及许多肽能类药物可以通过一种新型G蛋白偶联受体MrgprX2（Mas?related G protein coupled receptor X2）诱导肥大细胞脱颗粒。MrgprX2在变态反应、瘙痒、假性药敏方面扮演了重要的角色，这将有助于解释部分临床上肥大细胞经典IgE活化途径难以解释的现象，并为MC介导的相关疾病提供了潜在的治疗靶点。

关键词: 肥大细胞；免疫球蛋白E；受体, G-蛋白偶联；瘙痒症

Abstract: 【Abstract】 Mast cells （MC）, a major participant in inflammation and allergy, can initiate an early defense response to foreign invaders. Besides expressing high-affinity IgE receptor, MC also expresse a large number of G protein-coupled receptors （GPCRs）. Various studies have shown that cationic micromolecules represented by substance P and many peptidergic drugs can induce MC degranulation through a novel receptor, Mas-related G protein-coupled receptor X2 （MrgprX2）. MrgprX2 plays an important role in allergy, itching and pseudo-allergic drug reactions. It will help explain some clinical difficulties which can not be explained by classical IgE-dependent activation of MC, and provides potential therapeutic targets for MC-mediated diseases.

Key words: Mast cells, Immunoglobulin E, Receptors, G?protein?coupled, Pruritus

陈安薇白晓明王华. 肥大细胞非IgE途径活化新型受体mas相关G蛋白偶联受体X2的研究进展[J]. 中华皮肤科杂志, 2019, 52(2): 142-144.

Chen Anwei, Bai Xiaoming, Wang Hua. Mas-related G protein-coupled receptor X2: a novel receptor for non-IgE-dependent activation of mast cells[J]. Chinese Journal of Dermatology, 2019, 52(2): 142-144.

参考文献 26

［1］	Ali H. Mas⁃related G protein coupled receptor⁃X2: a potential new target for modulating mast cell⁃mediated allergic and inflammatory diseases［J］. J Immunobiol, 2016,1（4）. pii: 115.
［2］	Reber LL, Sibilano R, Mukai K, et al. Potential effector and immuno⁃regulatory functions of mast cells in mucosal immunity［J］. Mucosal Immunol, 2015,8（3）:444⁃463. doi: 10.1038/mi.2014. 131.
［3］	Rivera J, Gilfillan AM. Molecular regulation of mast cell activation［J］. J Allergy Clin Immunol, 2006,117（6）:1214⁃1226. doi: 10. 1016/j.jaci.2006.04.015.
［4］	Kaplan AP, Greaves M. Pathogenesis of chronic urticaria［J］. Clin Exp Allergy, 2009,39（6）:777⁃787. doi: 10.1111/j.1365⁃2222. 2009.03256.x.
［5］	McNeil BD, Pundir P, Meeker S, et al. Identification of a mast⁃cell⁃specific receptor crucial for pseudo⁃allergic drug reactions［J］. Nature, 2015,519（7542）:237⁃241. doi: 10.1038/nature14022.
［6］	Subramanian H, Gupta K, Lee D, et al. β⁃Defensins activate human mast cells via Mas⁃related gene X2［J］. J Immunol, 2013,191（1）:345⁃352. doi: 10.4049/jimmunol.1300023.
［7］	Subramanian H, Gupta K, Guo Q, et al. Mas⁃related gene X2 （MrgX2） is a novel G protein⁃coupled receptor for the anti⁃microbial peptide LL⁃37 in human mast cells: resistance to receptor phosphorylation, desensitization, and internalization［J］. J Biol Chem, 2011,286（52）:44739⁃44749. doi: 10.1074/jbc.M111. 277152.
［8］	Dong X, Han S, Zylka MJ, et al. A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons［J］. Cell, 2001,106（5）:619⁃632. doi: 10.1016/S0092⁃8674（01）00483⁃ 4.
［9］	Subramanian H, Gupta K, Ali H. Roles of Mas⁃related G protein⁃coupled receptor X2 on mast cell⁃mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases［J］. J Allergy Clin Immunol, 2016,138（3）:700⁃710. doi: 10.1016/ j.jaci.2016.04.051.
［10］	Solinski HJ, Gudermann T, Breit A. Pharmacology and signaling of Mas⁃related G protein⁃coupled receptors［J］. Pharmacol Rev, 2014,66（3）:570⁃597. doi: 10.1124/pr.113.008425.
［11］	Wu H, Zeng M, Cho EY, et al. The origin, , function and future research focus of a G protein⁃coupled receptor, Mas⁃related gene X2 （MrgX2）［J］. Prog Histochem Cytochem, 2015,50（1⁃2）:11⁃17. doi: 10.1016/j.proghi.2015.06.001.
［12］	Vonakis BM, Saini SS. New concepts in chronic urticaria［J］. Curr Opin Immunol, 2008,20（6）:709⁃716. doi: 10.1016/j.coi.2008.09. 005.
［13］	Fujisawa D, Kashiwakura J, Kita H, et al. Expression of Mas⁃related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria［J］. J Allergy Clin Immunol, 2014,134（3）:622⁃633. doi: 10.1016/j.jaci.2014.05.004.
［14］	Piliponsky AM, Gleich GJ, Bar I, et al. Effects of eosinophils on mast cells: a new pathway for the perpetuation of allergic inflammation［J］. Mol Immunol, 2002,38（16⁃18）:1369.
［15］	Hausmann O, Schnyder B, Pichler WJ. Etiology and pathogenesis of adverse drug reactions［J］. Chem Immunol Allergy, 2012,97:32⁃46. doi: 10.1159/000335614.
［16］	Azimi E, Reddy VB, Shade KC, et al. Dual action of neurokinin⁃1 antagonists on Mas⁃related GPCRs［J］. JCI Insight, 2016,1（16）:e89362. doi: 10.1172/jci.insight.89362.
［17］	Mertes PM, Alla F, Tréchot P, et al. Anaphylaxis during anesthesia in France: an 8⁃year national survey［J］. J Allergy Clin Immunol, 2011,128（2）:366⁃373. doi: 10.1016/j.jaci.2011.03.003.
［18］	Bulfone⁃Paus S, Nilsson G, Draber P, et al. Positive and negative signals in mast cell activation［J］. Trends Immunol, 2017,38（9）:657⁃667. doi: 10.1016/j.it.2017.01.008.
［19］	Zhang T, Che D, Liu R, et al. Typical antimicrobials induce mast cell degranulation and anaphylactoid reactions via MRGPRX2 and its murine homologue MRGPRB2［J］. Eur J Immunol, 2017,47（11）:1949⁃1958. doi: 10.1002/eji.201746951.
［20］	Homey B, Steinhoff M, Ruzicka T, et al. Cytokines and chemokines orchestrate atopic skin inflammation［J］. J Allergy Clin Immunol, 2006,118（1）:178⁃189. doi: 10.1016/j.jaci.2006.03.047.
［21］	Wilson SR, Thé L, Batia LM, et al. The epithelial cell⁃derived atopic dermatitis cytokine TSLP activates neurons to induce itch［J］. Cell, 2013,155（2）:285⁃295. doi: 10.1016/j.cell.2013.08.057.
［22］	Lee MG, Dong X, Liu Q, et al. Agonists of the Mas⁃related gene （Mrgs） orphan receptors as novel mediators of mast cell⁃sensory nerve interactions［J］. J Immunol, 2008,180（4）:2251⁃2255.
［23］	Gaudenzio N, Sibilano R, Marichal T, et al. Different activation signals induce distinct mast cell degranulation strategies［J］. J Clin Invest, 2016,126（10）:3981⁃3998. doi: 10.1172/JCI85538.
［24］	Karhausen J, Abraham SN. How mast cells make decisions［J］. J Clin Invest, 2016,126（10）:3735⁃3738. doi: 10.1172/JCI90361.
［25］	Hagiwara D, Miyake H, Morimoto H, et al. Studies on neurokinin antagonists. 1. the design of novel tripeptides possessing the glutaminyl⁃D⁃tryptophylphenylalanine sequence as substance P antagonists［J］. J Med Chem, 1992,35（11）:2015⁃2025.
［26］	Lansu K, Karpiak J, Liu J, et al. In silico design of novel probes for the atypical opioid receptor MRGPRX2［J］. Nat Chem Biol, 2017,13（5）:529⁃536. doi: 10.1038/nchembio.2334.

肥大细胞非IgE途径活化新型受体mas相关G蛋白偶联受体X2的研究进展

Mas-related G protein-coupled receptor X2: a novel receptor for non-IgE-dependent activation of mast cells

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