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，我们研究了儿童正常主动脉和疾病后期各种细胞因子的定位，并分析了细胞初始化的免疫表型特征，结果表明，一种特异性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)研究饮食诱导大鼠动脉粥样硬化免疫成分的时空分布。表面双免疫染色细胞成分分析显示，在病变形成初期，T淋巴细胞的浸润最为突出。(3)在缺乏T淋巴细胞的胸腺裸大鼠饮食诱导的主动脉病变中，我们研究了体内T淋巴细胞与动脉粥样硬化相关的功能，结果表明，与对照动物相比，裸大鼠的病变在大小上发展有限，而内膜巨噬细胞的泡沫细胞转化更为突出。(4)我们建立了动脉内膜的体外模型，用于三维分析与动脉粥样硬化相关的血管细胞相互作用；利用血单核细胞SND内皮细胞修饰的低密度脂蛋白诱导脂肪条纹样病变。

(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.