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Role of Macrophages and Immune Cells in Atherogenesis

巨噬细胞和免疫细胞在动脉粥样硬化形成中的作用

基本信息

批准号：
04454181
负责人：
WATANABE Teruo
金额：
$ 3.58万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454181/
关键词：
Atherogenesis Atherosclerosis Macrophages T lymphocytes Immune Mechanism Foam Cells In Vitro Model Hypercholesterolemia

项目摘要

(1) To elucidate the role of T lymphcytes and macrophages in human atherosclerosis, the localization of various cytokines with an analysis of immunophenotypic featues of the cellular initlrates was studied in normal aortas from children and in later phases of the disease, and the results suggested that a specific in situ, cell mediated hypersensitivity plays a pivotal role in the nascent as well as the progression stages of human atherogenesis.(2) Temporal and spatial distribution of the immunologic components of atherosclerosis was studied in a diet-induced rat model. Analysis of cellular components by en face double immunostaining revealded that infiltration of T lymphocytes was most prominent in the incipient phase of lesion formation.(3) In vivo functions of T lymphocytes relevant to atherogenesis was studied in diet-induced aortic lesions of athymic nude rats lacking T lymphocytes, and the results obtained demonstrated that, in comparison with control animals, the lesion development was limited in size, whereas foam cell transformation of intimal macrophages was more prominent in nude rats.(4) We developed an in vitro model of the arterial intima for three dimensional analysis of vascular cell interactions relevant to atherogenesis, and ; induced fatty streak-like lesions by the use of blood mononulcear cells snd endothelial cell-modified low density lipoprotein.

(1)为了阐明T淋巴细胞和巨噬细胞在人类动脉粥样硬化中的作用，我们研究了儿童正常动脉粥样硬化和晚期动脉粥样硬化中各种细胞因子的定位，并分析了细胞起始物的免疫表型特征。结果表明，一种特异的原位细胞介导的超敏反应在人类动脉粥样硬化的新生和进展阶段起着关键作用。(2)在饮食诱导的大鼠动脉粥样硬化模型上，研究了动脉粥样硬化免疫组分的时空分布。细胞成分的分析，正面双重免疫染色显示，T淋巴细胞的浸润是最突出的病变形成的初期阶段。(3)在缺乏T淋巴细胞的无胸腺裸大鼠的饮食诱导的主动脉病变中，研究了与动脉粥样硬化形成相关的T淋巴细胞的体内功能，所获得的结果表明，与对照动物相比，病变发展的大小有限，而内膜巨噬细胞的泡沫细胞转化在裸大鼠中更为突出。(4)我们建立了一个体外动脉内膜模型，用于动脉粥样硬化形成相关血管细胞相互作用的三维分析，并通过使用血单核细胞和内皮细胞修饰的低密度脂蛋白诱导脂肪条样病变。