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首页> 外文期刊>Journal of Lipid Research >Altered immune responses in apolipoprotein E-deficient mice.
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Altered immune responses in apolipoprotein E-deficient mice.

机译:载脂蛋白E缺乏症小鼠的免疫应答改变。

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Apolipoprotein E (apoE) is a 34 kDa glycosylated protein with multiple biological properties. In addition to its role in cholesterol transport, apoE has in vitro immunomodulatory properties. Recent data suggest that these immunomodulatory effects of apoE may be biologically relevant, and apoE-deficient mice have altered immune responses after bacterial inoculation and increased susceptibility to endotoxemia induced by lipopolysaccharide (LPS). To better understand the mechanism by which apoE-modulates immune responses, we tested the role of human apoE isoforms in assays of human T cell proliferation, and analyzed the immune responses of apoE-deficient mice. Both the E3 and E4 isoforms of apoE induced similar suppression of human lymphocyte function in assays of T cell proliferation, including mitogenic responses to phytohaemagglutin (PHA), stimulation of the T cell receptor with alphaCD3, and antigen-specific response to tetanus toxoid. ApoE-deficient mice showed no quantitative differences in thymic, splenic, or bone marrow lymphocyte populations, nor were there in vitro abnormalities in splenocyte proliferation after stimulation with alphaCD3 to suggest an inherent T cell defect in apoE-deficient mice. ApoE deficient animals, however, had significantly higher levels of antigen-specific IgM after immunization with tetanus toxoid, and impaired delayed type hypersensitivity responses as compared to control C57-BL/6 mice.These results support a growing body of evidence demonstrating an interplay between lipid metabolism and immune responses, and suggest that apoE plays a biologically relevant role in regulating humoral and cell-mediated immunity.
机译:载脂蛋白E(apoE)是一种具有多种生物学特性的34 kDa糖基化蛋白。除了在胆固醇转运中的作用外,apoE还具有体外免疫调节特性。最近的数据表明,apoE的这些免疫调节作用可能与生物学有关,并且apoE缺陷型小鼠在细菌接种后改变了免疫反应,并增加了脂多糖(LPS)引起的对内毒素血症的易感性。为了更好地了解apoE调节免疫反应的机制,我们测试了人类apoE亚型在人类T细胞增殖测定中的作用,并分析了apoE缺陷小鼠的免疫反应。在T细胞增殖试验中,apoE的E3和E4亚型都诱导了人类淋巴细胞功能的类似抑制,包括对植物血凝素(PHA)的促有丝分裂反应,用alphaCD3刺激T细胞受体以及对破伤风类毒素的抗原特异性反应。缺乏ApoE的小鼠在胸腺,脾脏或骨髓淋巴细胞群中没有定量差异,在用αCD3刺激后,脾细胞增殖的体外也没有异常,表明在缺乏ApoE的小鼠中固有的T细胞缺陷。然而,与对照C57-BL / 6小鼠相比,破伤风类毒素免疫后ApoE缺陷动物的抗原特异性IgM水平明显升高,并且迟发型超敏反应受损,这些结果支持了越来越多的证据表明,两者之间存在相互作用脂代谢和免疫反应,并表明apoE在调节体液和细胞介导的免疫中起着生物学相关的作用。

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