Immunoglobulin treatment suppresses atherosclerosis in apolipoprotein E-deficient mice via the Fc portion.
Immunoglobulin treatment suppresses atherosclerosis in apolipoprotein E-deficient mice via the Fc portion.
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DOI：
10.1152/ajpheart.00926.2002
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发表时间：
2003-08
期刊：
影响因子：
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通讯作者：
Zuyi Yuan;C. Kishimoto;H. Sano;K. Shioji;Yang Xu;M. Yokode
中科院分区：
文献类型：
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作者：
Zuyi Yuan;C. Kishimoto;H. Sano;K. Shioji;Yang Xu;M. Yokode
动脉粥样硬化与免疫激活有关。免疫球蛋白用于治疗免疫介导的疾病。本文探讨了免疫球蛋白Fc区在载脂蛋白E缺陷小鼠实验性动脉粥样硬化中的作用及其机制。在喂食含0.3%胆固醇的高脂饮食的小鼠中诱导实验性动脉粥样硬化。在8、12和16周内，隔日腹腔注射1 g/kg/天的人完整免疫球蛋白或人免疫球蛋白的F（ab '）2片段。脂肪条纹形成和纤维脂肪斑块明显抑制小鼠接受完整的免疫球蛋白为8，12和16周。相反，接受F（ab '）2片段的小鼠动脉粥样硬化病变没有改善。免疫组织化学分析显示，在接受完整免疫球蛋白的小鼠中，脂肪条纹病变中的巨噬细胞积聚受到抑制，但在接受F（ab '）2片段的小鼠中则没有。此外，与人血清白蛋白处理的小鼠相比，免疫球蛋白处理的小鼠脾细胞的细胞毒活性显著抑制，但F（ab '）2片段处理的小鼠没有。病变面积的差异与血脂水平的任何显著变化无关。免疫球蛋白治疗由于Fc受体介导的抗炎和免疫调节作用而显著抑制动脉粥样硬化。免疫球蛋白的抗动脉粥样硬化作用可能与抑制致动脉粥样硬化性T细胞的细胞毒活性和减少巨噬细胞在病变中的积聚有关。
Atherosclerosis is associated with immune activation. Immunoglobulin is used for the treatment of immune-mediated diseases. The mechanisms and importance of the Fc portion of immunoglobulin upon experimental atherosclerosis in apolipoprotein E-deficient mice were examined. Experimental atherosclerosis was induced in mice fed a high-fat diet containing 0.3% cholesterol. Over 8, 12, and 16 wk, on alternate days, mice were treated with an intraperitoneal injection of either 1 g.kg-1.day-1 of human intact immunoglobulin or F(ab')2 fragments of human immunoglobulin. Fatty streak formation and fibrofatty plaques were markedly suppressed in mice that received intact immunoglobulin for 8, 12, and 16 wk. In contrast, atherosclerotic lesions were not ameliorated in mice that received F(ab')2 fragments. Immunohistochemical analysis revealed that macrophage accumulation in the fatty streak lesions was suppressed in mice received intact immunoglobulin but not in those that received F(ab')2 fragments. In addition, the cytotoxic activities of splenocytes from immunoglobulin-treated mice, but not from F(ab')2 fragment-treated mice, were significantly suppressed compared with those from human serum albumin-treated mice. Differences in lesion area did not correlate with any significant alterations in serum lipid levels. Immunoglobulin therapy markedly suppressed atherosclerosis due to Fc receptor-mediated anti-inflammatory and immunomodulating actions. The antiatherosclerotic effects of immunoglobulin may be related to the suppression of cytotoxic activity of atherogenic T cells and the reduction of macrophage accumulation in the lesions.