Label-Free Quantitative Proteomic Profiling of LAD2 Mast Cell Releasates Reveals the Mechanism of Tween-80-Induced Anaphylactoid Reaction.
Label-Free Quantitative Proteomic Profiling of LAD2 Mast Cell Releasates Reveals the Mechanism of Tween-80-Induced Anaphylactoid Reaction.
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LAD2 肥大细胞释放物的无标记定量蛋白质组学分析揭示了 Tween-80 诱导的类过敏反应的机制。
DOI：
10.1002/prca.201900065
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Cao Yong-Xiao
中科院分区：
文献类型：
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作者：
Mi Yan-Ni;Yan Ping-Ping;Di Jia;Cao Lei;Xiao Xue;Liu Dong-Zheng;Cao Yong-Xiao
目的吐温-80是引起类过敏反应的重要原因之一。然而，其机制尚不清楚。通过检测肥大细胞对吐温-80反应的蛋白质组学特征，探讨类过敏反应的机制。实验设计采用无标记的LC MS/MS蛋白质组学方法分析吐温-80刺激的变态反应性疾病实验室2(LAD2)肥大细胞的释放。对蛋白质组学结果进行生物信息学分析。结果生物信息学分析表明，细胞内吞作用、活化B细胞核因子轻链增强子(NF-κB)和钙信号通路在吐温-80诱导的LAD2细胞活化中起重要作用。与对照组相比，吐温-80组肌动蛋白相关蛋白2/3复合体、空泡蛋白分类相关蛋白、转录因子p105和p65的磷酸化、肌醇1，4，5-三磷酸受体的磷酸化、磷脂酶Cγ(PLCγ)和蛋白激酶C(PKC)的表达显著增加。吐温-80可能通过内吞作用内化，通过PLCγ/PKC途径介导钙内流而引起脱颗粒，通过NF-κB途径促进炎症介质的产生，从而引起类过敏反应。
PurposeTween‐80 is one of the most important causes resulting in anaphylactoid reaction. However, its mechanism remains unclear. Proteomic characterizations of mast cells’ excreta in response to Tween‐80 are assayed to investigate the mechanism of anaphylactoid reaction.Experimental designA label‐free LCMS/MS‐based proteomics is used to analyze Tween‐80‐stimulated Laboratory of Allergic Diseases 2 (LAD2) mast cells releasates. The results of proteomic are analyzed by bioinformatics analysis. Western blotting is used to verify the expression of proteins.ResultsOverall, endocytosis, nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), and calcium signaling pathways play important roles in Tween‐80‐induced LAD2 cells activation by bioinformatics analysis. The expressions of relative proteins including actin‐related protein 2/3 complexes, vacuolar protein sorting‐associated protein, phosphorylation of transcription factor of P105 and P65, phosphorylation of inositol 1,4,5‐trisphosphate receptor (IP3R), phosphoinositide phospholipase Cγ (PLCγ), and protein kinase C (PKC), are significantly increased in Tween‐80 group compared to control. Tween‐80 might be internalized via endocytosis, which induces degranulation by PLCγ/PKC pathways mediated calcium influx, and promotes the generation of inflammatory mediators via NF‐κB pathway resulting in anaphylactoid reaction.