Role of G protein coupled receptor (GPCR)-mediated signals in the activation of immune cell.

G 蛋白偶联受体 (GPCR) 介导的信号在免疫细胞激活中的作用。

基本信息

批准号：
11670324
负责人：
NAKASHIMA Manabu
金额：
$ 0.83万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670324/
关键词：
G protein coupled receptor antigen receptor signal transduction Th1 cell Th2 cells B cells gene targeting cytokine production ヒスタミンHI受容体欠損マウス Btk ZAP-7 Gタンパク結合型受容体(GPCR)TH1 Th2バランス

项目摘要

It has been reported that T and B cells express various kinds of G protein coupled receptors (GPCR) on their cell surface. In the present study, we investigated the effects of GPCR-mediated signals on the antigen receptor-mediated signal transduction in T and B cells upon antigen stimulation. The present studies clarified the presence of a close cross-talk between GPCR-mediated signaling and antigen receptor-mediated signal transduction. GPCR Gaq coupled to histamine H1 receptor (H1R) and Gas associates with histamine H2R.Mature T and B cells express both H1R and H2R.We previously established H1R- and H2R-deficient mice by gene targeting. The H1R-deficient T and B cells showed a remarkably reduced responses against antigen stimulation or crosslinking of the receptor by anti-CD3 or anti-IgM antibody, indicating that signal (s) from Gaq plays a essential role in antigen receptor-mediated signal transduction. Histamine is one of major chemical mediators of immediate-type hypersensitivity. … More Pharmacological studies have been also suggested that histamine may affect Th types of helper T cells via a signal (s) from their receptors. Allergic reaction elicited in the ears as well as cytokine production from spleen cells of these mutant mice were examined upon stimulation with antigen. The allergic reactions induced by histamine, anti-DNP IgE and OVA were significantly inhibited in H1R-deficient mice. Serotonin increased vascular permeability in H1R-deficient mice, however the intensity was lesser than that of wild-type mice. Whereas H2R-deficient mice exhibited normal allergic reactions. IFNγ production was markedly reduced in H1R-deficient mice, whereas that was increased in H2R-deficient mice. IL-13 production was greatly enhanced in H2R-deficient mice. Such enhancement was also observed in H1R-deficient mice. These results suggest that increased vascular permeability in cutaneous anaphylaxis is mainly regulated by H1R signaling but not by H2R signaling. Moreover, the signal from H1R may play a crucial role in positive regulation of Th1 activation, whereas that from H2R may negatively regulate Th1 as well as Th2 activation. Less

据报道，T和B细胞在其细胞表面表达各种G蛋白偶联受体（GPCR）。在本研究中，我们研究了GPCR介导的信号对抗原刺激时T和B细胞中T和B细胞中抗原受体介导的信号转移的影响。本研究阐明了GPCR介导的信号传导和抗原受体介导的信号转移之间存在密切的串扰。 GPCR GAQ与组胺H1受体（H1R）偶联，并与组胺H2R。含量H2R和B细胞相关的GPCR。T和B细胞表达H1R和H2R。 H1R缺陷型T和B细胞显示出抗CD3或抗IGM抗体对受体的抗原刺激或交联的反应明显降低，表明GAQ的信号在抗原受体受体介导的信号转移中起着至关重要的作用。组胺是直接型超敏反应的主要化学介质之一。 …也有更多的药理学研究表明，组胺可能通过其受体的信号影响TH类型的辅助T细胞。在用抗原刺激后检查了耳朵中引起的过敏反应以及这些突变小鼠脾细胞的细胞因子产生。 H1R缺陷型小鼠在组胺，抗DNP IgE和OVA引起的过敏反应显着抑制。 5-羟色胺增加了H1R缺陷小鼠的血管通透性，但是强度比野生型小鼠的强度要小。而H2R缺陷的小鼠暴露了正常的过敏反应。 H1R缺陷型小鼠中IFNγ的产生显着降低，而H2R缺陷型小鼠的产生。 H2R缺陷型小鼠的IL-13产生大大增强。在H1R缺陷小鼠中也观察到了这种增强。这些结果表明，皮肤过敏反应中的血管通透性增加主要受H1R信号的调节，而不是由H2R信号传导调节。此外，来自H1R的信号可能在TH1激活的正调控中起关键作用，而H2R的信号可能会对TH1和TH2激活负面调节。较少的