Matsumoto T, Saito E, Watanabe H, Fujioka T, Yamada T, Takahashi Y, Ueno T, Tochihara T, Kanmatsuse K
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Atherosclerosis. 1998 Jul;139(1):95-106. doi: 10.1016/s0021-9150(98)00066-5.
To investigate the role of activated T lymphocytes in the formation of atherosclerotic lesions, we studied the influence of FK506, an immunosuppressant, on the development of atherosclerosis in cholesterol-fed rabbits. New Zealand White rabbits fed on a 1.5% cholesterol diet were administered FK506 at 0.05 mg/kg (n = 12), 0.1 mg/kg (n = 12) or isotonic saline (as the control, n = 12) intramuscularly three times a week for 12 weeks. Although FK506 treatment did not affect plasma lipid levels, it caused an increase in the development of atherosclerotic lesions in a dose-dependent manner. Immunohistochemical analysis of the aorta after 8 weeks on the diet revealed that the ratio of T lymphocytes to the total number of cells in the plaques decreased significantly in the FK506 treated rabbits compared to the control rabbits. In culture, FK506 did not affect smooth muscle cell proliferation and cholesteryl ester formation in the macrophages. In contrast, culture medium from lymphocytes stimulated by concanavalin A decreased the accumulation of cholesteryl ester in the macrophages. This effect was inhibited by the culture medium in the presence of FK506. These findings suggest that activated T lymphocytes may inhibit intracellular cholesterol accumulation in atherosclerotic plaque.
为了研究活化的T淋巴细胞在动脉粥样硬化病变形成中的作用，我们研究了免疫抑制剂FK506对高胆固醇喂养兔子动脉粥样硬化发展的影响。给食用1.5%胆固醇饮食的新西兰白兔每周三次肌肉注射0.05mg/kg（n = 12）、0.1mg/kg（n = 12）的FK506或等渗盐水（作为对照，n = 12），持续12周。虽然FK506治疗不影响血浆脂质水平，但它以剂量依赖的方式导致动脉粥样硬化病变的发展增加。饮食8周后对主动脉进行免疫组织化学分析发现，与对照兔子相比，FK506治疗的兔子斑块中T淋巴细胞与细胞总数的比例显著降低。在培养中，FK506不影响平滑肌细胞增殖和巨噬细胞中胆固醇酯的形成。相反，伴刀豆球蛋白A刺激的淋巴细胞培养基减少了巨噬细胞中胆固醇酯的积累。在FK506存在的情况下，这种作用被培养基抑制。这些发现表明，活化的T淋巴细胞可能抑制动脉粥样硬化斑块中的细胞内胆固醇积累。
