A MOLECULAR BIOLOGICAL STUDY ON CARDIAC DENDRITIC CELL OF THE AUTOIMMUNE CARDIOMYOPATHY

自身免疫性心肌病心脏树突状细胞的分子生物学研究

基本信息

批准号：
11838015
负责人：
IZUMI Tohru
金额：
$ 2.3万
依托单位：
KITASATO 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-11838015/
关键词：
DENDRITIC CELL MYOCARDITIS CARDIOMYOPATHY HYBRIDOMA myocardifis hybridome cardiomyopathy cytokive

项目摘要

The cardiac dendritic cell, a new matrix cell in the myocardium, must play an important role in the immunoresponse of the heart. Through several studies on rat experimental autoimmune myocarditis, EAM, the provoked dendritic cell revealed an activation of antigen specific T cells and initiation of inflammatory lesions in the heart as an antigen presenter. Thus, the present study, a molecular biological study on cardiac dendritic cell of the autoimmune cardiomyopathy was designed to elucidate, 1. the role of the dendritic cell in the human myocarditis and cardiomyopathy, 2. a method to establish an alternative artificial cell of the dendritic cell that will work well in in vivo and in vitro experiments, and 3. the role of dendritic cell in the stage of chronic heart failure.Firstly, in human myocarditis, the dendritic cell frequently occurs in the acute phase. And, in persistent inflammatory lesion, the grade of the cell infiltrates corresponded well to the severity of the myocarditis. … More Dilated cardiomyopathy has also documented the dendritic infiltrates, but its occurrence has been far less in this disease than in acute myocarditis. Cellular characteristics of the human heart are very similar to ones of EAM in surface antigens (positive HLA-DR and negative CD68) and have also the same morphology except for one exception, cytoplasmic processing like a glove. Secondly, to identify a T cell clone that is specific respond with the cardiac myosin, we tried to establish a hybridoma cell. The hybridoma was designed to present MHC antigen on the cell surface. Lymphocytes were isolated from EAM rats, and were fused with B cell lymphoma originated from Balb/c mouse (M12.4.5). Consequently we obtained the cell line, MLEW.This hybridoma was able to mediate a specific activation of EAM lymphocyte with the cardiac myosin, and, when used with ^<51>Cr release it was documented to damage the cardiocyte. Thirdly, the dendritic cell's role in chronic heart failure was experimentally confirmed. In heart failure mediated by autoimmune mechanisms, T cells transform to TH1 intensively which contributes to acute worsening. On the other hand, for remission of this state, T cell shift from TH1 to TH2. The dendrites have a close relationship with both pathways. Less

心肌中的一种新基质细胞的心脏树突状细胞必须在心脏的免疫反应中起重要作用。通过对大鼠实验性自身免疫性心肌炎的多项研究，EAM证明了树突状细胞表明，抗原特异性T细胞的激活以及心脏中炎症性病变的主动性作为抗原演示者。这是本研究，这是一项针对自身免疫性心肌病的心脏树突状细胞的分子生物学研究，旨在阐明1。树突状细胞在人体心肌和心肌病中的作用，2。一种方法，是一种在vivo和vivo中可以很好地建立在vivo和vetro中依靠的替代性人工细胞的方法。慢性心力衰竭的阶段。首先，在人体心肌炎中，树突状细胞经常发生在急性期。并且，在持续的炎症病变中，细胞浸润的等级与心肌炎的严重程度相对应。 …更扩张的心肌病也记录了树突状浸润，但在这种疾病中的发生远低于急性心肌炎。人心脏的细胞特征与表面抗原中的EAM的细胞特征非常相似（阳性HLA-DR和阴性CD68），并且具有相同的形态，除了一个例外，像手套一样的细胞质加工。其次，为了确定特定于心脏肌球蛋白的特异性响应的T细胞克隆，我们试图建立杂交瘤细胞。杂交瘤设计用于在细胞表面呈现MHC抗原。从EAM大鼠中分离出淋巴细胞，并与B细胞淋巴瘤融合起来源自BALB/C小鼠（M12.4.5）。因此，我们获得了细胞系MLEW。该杂交瘤能够用心脏肌球蛋白介导特异性EAM淋巴细胞的激活，当与 ^<51> CR释放一起使用时，它已记录下来以损害心脏细胞。第三，实验证实了树突状细胞在慢性心力衰竭中的作用。在由自身免疫机制介导的心力衰竭中，T细胞强烈转化为Th1，这有助于急性担心。另一方面，为了缓解该状态，T细胞从Th1转移到Th2。树突与这两种途径都有密切的关系。较少的