Role of Macrophages and Immune Cells in Atherogenesis

(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，通过对儿童正常主动脉和疾病后期的免疫表型特征的分析，研究了各种细胞因子的定位，结果表明，一种特定的原位细胞介导的超敏反应在人类动脉粥样硬化的初期和进展阶段中起着关键作用。(2)在饮食诱导的大鼠模型中，研究了动脉粥样硬化免疫成分的时空分布。通过En Face双重免疫染色分析细胞成分，发现在病变形成的初期，T淋巴细胞的渗透最为突出。(3)在饮食诱导的缺乏T淋巴细胞的裸鼠主动脉病变中，对与动脉粥样硬化相关的T淋巴细胞的体内功能进行了研究，结果表明，与对照组相比，病变的发展有限，而裸鼠动脉内膜巨噬细胞的泡沫细胞转化更明显。(4)我们建立了一种体外动脉内膜模型，用于三维分析与动脉粥样硬化相关的血管细胞相互作用。用外周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。

(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.