Increased expression of cell adhesion molecule 1 by mast cells as a cause of enhanced nerve-mast cell interaction in a hapten-induced mouse model of atopic dermatitis
Increased expression of cell adhesion molecule 1 by mast cells as a cause of enhanced nerve-mast cell interaction in a hapten-induced mouse model of atopic dermatitis
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DOI：
10.1111/bjd.12108
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发表时间：
2013-04-01
影响因子：
10.3
通讯作者：
Ito, A.
中科院分区：
文献类型：
--
作者：
Hagiyama, M.;Inoue, T.;Ito, A.
背景神经免疫紊乱参与了特应性皮炎（AD）的发病机制，部分通过增强感觉神经-皮肤肥大细胞的相互作用。细胞粘附分子1（cell adhesion molecule 1，CADM 1）是一种介导与交感神经粘附和通讯的肥大细胞粘附分子。目的通过比较AD小鼠模型皮损和非皮损皮肤肥大细胞中CADM 1的表达水平，探讨肥大细胞CADM 1在AD发病机制中的作用。方法采用激光捕获显微切割技术分别收集AD样皮肤病变和非病变皮肤肥大细胞，观察肥大细胞中CADM 1的表达变化对感觉神经-肥大细胞相互作用的影响。逆转录-聚合酶链反应和CADM 1免疫组化检测CADM 1表达。在共培养中，背根神经节（DRG）神经突和IC 2肥大细胞之间的粘附进行了分析，通过加载飞秒激光诱导的脉冲力的神经突伴随IC 2细胞，而细胞通信进行监测的IC 2细胞反应（[Ca 2 +]（i）增加）后，神经特异性刺激剂诱导的DRG activation.Results AD样病变肥大细胞表达的CADM 1转录比non-lesional细胞的3倍。这在蛋白质水平上得到了支持，通过免疫组织化学显示。在共培养中，CADM 1在IC 2细胞中的过表达加强了DRG神经突-IC 2细胞粘附，并使响应DRG激活的IC 2细胞数量增加了一倍。一个功能阻断抗CADM 1抗体废除这些影响的剂量依赖manners.Conclusions肥大细胞中CADM 1的表达增加似乎是一个原因，增强感觉神经肥大细胞的相互作用，在半抗原诱导的小鼠模型AD。
Background Neuroimmunological disorders are involved in the pathogenesis of atopic dermatitis (AD), partly through enhanced sensory nerve-skin mast cell interaction. Cell adhesion molecule 1 (CADM1) is a mast-cell adhesion molecule that mediates the adhesion to, and communication with, sympathetic nerves.Objectives To investigate the role of mast cell CADM1 in the pathogenesis of AD, CADM1 expression levels by comparing between lesional and nonlesional skin mast cells of an AD mouse model, which was developed by repeated application of trinitrochlorobenzene, and to examine, in cocultures, how the alterations in CADM1 detected in lesional mast cells might affect the sensory nerve-mast cell interaction.Methods AD-like lesional and nonlesional skin mast cells were collected separately by laser capture microdissection. CADM1 expression was examined by reverse transcription-polymerase chain reaction and CADM1 immunohistochemistry. In cocultures, adhesion between dorsal root ganglion (DRG) neurites and IC2 mast cells was analysed by loading a femtosecond laser-induced impulsive force on neurite-attendant IC2 cells, while cellular communication was monitored as the IC2 cellular response ([Ca2+](i) increase) after nerve-specific stimulant-induced DRG activation.Results AD-like lesional mast cells expressed three-fold more CADM1 transcripts than nonlesional cells. This was supported at the protein level, shown by immunohistochemistry. In coculture, CADM1 overexpression in IC2 cells strengthened DRG neurite-IC2 cell adhesion and doubled the population of IC2 cells responding to DRG activation. A function-blocking anti-CADM1 antibody abolished these effects in a dose-dependent manner.Conclusions Increased expression of CADM1 in mast cells appeared to be a cause of enhanced sensory nerve-mast cell interaction in a hapten-induced mouse model of AD.