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Crosstalk of immune and nervous systems by 3-D imaging

3D 成像对免疫系统和神经系统的串扰

基本信息

批准号：
10044312
负责人：
NAKANISHI Mamoru
金额：
$ 3.39万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10044312/
关键词：
Allergy Mast cells Bradykinin Confocal laser scanning microscopy Calcium ion NK-1 antagonist Substance P Nerves サブスタンスP 好塩基球共焦点レーザ顕微鏡アンタゴニスト

项目摘要

Communication between nerves and mast cells is a prototypic demonstration of neuroimmune interaction. However, whether mast cell activation occurs as a direct response to neuronal activation or requires an intermediary cell is unclear. Addressing this issue, we used an in vitro coculture approach comprising cultured murine superior cervical ganglia and rat leukemia basophilic cells (RBLs ; possesses properties of mucosal-type mast cells). Following loading with the calcium fluorophore, Fluo-3, neurite-RBL units (separated by <50nm) were examined by confocal laser scanning microscopy. Addition of bradykinin, or scorpion venom, dose-dependently elicited neurite activation (i.e., CaィイD12+ィエD1 mobilization) and, after a lag period, RBL CaィイD12+ィエD1 mobilization. Neither bradykinin nor scorpion venom had any direct effect on the RBLs in the absence of neurites. Addition of a neutralizing substance P Ab or a neurokinin (NK)-1 receptor antagonist, but not an NK-2 receptor antagonist, dose-dependently prevented the RBL activation that resulted as a consequence of neural activation by either bradykinin or scorpion venom. These data illustrate that nerve-mast cell cross-talk can occur in the absence of an intermediary transducing cell and that the neuropeptide substance P, operating via NK-1 receptors, is an important mediator of this communication. Our findings have implications for the neuroimmune signaling cascades that are likely to occur during airways inflammation, intestinal hypersensitivity, and other conditions in which mast cells feature.

神经和肥大细胞之间的通讯是神经免疫相互作用的原型演示。然而，肥大细胞激活是作为对神经元激活的直接反应而发生还是需要中间细胞尚不清楚。为了解决这个问题，我们采用了体外共培养方法，包括培养的小鼠颈上神经节和大鼠白血病嗜碱性细胞（RBL；具有粘膜型肥大细胞的特性）。加载钙荧光团、Fluo-3、神经突-RBL 单位（间隔<50nm）后，通过共焦激光扫描显微镜检查。添加缓激肽或蝎毒，剂量依赖性地引发神经突激活（即 CaィイD12+ィエD1 动员），并且在滞后期后，RBL CaィイD12+ィエD1 动员。在没有神经突的情况下，缓激肽和蝎毒都不会对 RBL 产生任何直接影响。添加中和物质 P Ab 或神经激肽 (NK)-1 受体拮抗剂（而非 NK-2 受体拮抗剂）可剂量依赖性地阻止因缓激肽或蝎毒神经激活而导致的 RBL 激活。这些数据表明，神经肥大细胞串扰可以在没有中间转导细胞的情况下发生，并且通过 NK-1 受体起作用的神经肽物质 P 是这种通信的重要介质。我们的研究结果对气道炎症、肠道过敏和肥大细胞特征的其他病症期间可能发生的神经免疫信号级联具有影响。