Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice
Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice
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DOI：
10.1016/j.atherosclerosis.2005.11.033
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发表时间：
2006-11-01
期刊：
影响因子：
5.3
通讯作者：
Shah, Prediman K.
中科院分区：
文献类型：
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作者：
Faria-Neto, Jose R.;Chyu, Kuang-Yuh;Shah, Prediman K.
磷酸胆碱（PC）头基是LDL氧化暴露的新抗原之一，可以引发免疫应答。肺炎链球菌（其细胞壁上带有PC）主动免疫可降低高胆固醇血症小鼠的动脉粥样硬化，这种作用归因于对PC的免疫应答。在这项研究中，我们测试的假设，被动免疫与单克隆抗PC IgM抗体可以在小鼠模型的天然主动脉和静脉移植动脉粥样硬化的动脉粥样硬化保护。将来自16周龄供体雄性apoE敲除小鼠的下腔静脉移植到年龄匹配的雄性受体apoE敲除小鼠的右颈动脉中。术前和术后4周评价抗PC IgM滴度。对于免疫方案，从手术当天开始，单独的一组小鼠接受每周腹膜内注射单克隆抗PC IgM（400 μ g），持续4周。对照接受PBS或合并的多克隆IgM。术后4周抗PC IgM滴度显著升高。抗PC IgM被动免疫减少静脉移植斑块大小和新生内膜厚度，导致更大的管腔面积;此外，免疫减少斑块的炎性细胞含量。对已确定的自体主动脉粥样硬化病变无显著影响。免疫接种不影响循环胆固醇水平。总之，我们的数据表明，被动免疫抗PC IgM显着减少静脉移植病变的大小与较少的炎症表型，而不影响胆固醇水平，表明动脉粥样硬化保护性免疫反应PC。对已建立的自体主动脉病变缺乏影响可能是由于治疗持续时间短和/或与静脉移植物动脉粥样硬化的进展性病变相比，对已建立病变的疗效降低。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Phosphorylcholine (PC) headgroup is one of the neoantigens exposed by LDL oxidation that can elicit an immune response. Active immunization with Streptococcus pneumoniae, which bears PC on its cell wall, reduced atherosclerosis in hypercholesterolemic mice and this effect was attributed to an immune response to PC. In this study we tested the hypothesis that passive immunization with a monoclonal anti-PC IgM antibody can be athero-protective in a murine model of native aortic and vein graft atherosclerosis. Inferior vena cava from 16-week-old donor male apoE-null mice was grafted into right carotid artery of age-matched male recipient apoE-null mice. Anti-PC IgM titers were evaluated before and 4 weeks after surgery. For the immunization protocol, a separate group of mice received weekly intraperitoneal injection of monoclonal anti-PC IgM (400 mu g) for 4 weeks, starting the day of surgery. Controls received PBS or pooled polyclonal IgM. Anti-PC IgM titres significantly increased at 4 weeks following surgery. Passive immunization with anti-PC IgM reduced vein graft plaque size and neointimal thickness resulting in a larger luminal area; in addition immunization reduced the inflammatory cell content of the plaques. There was no significant effect on the established native aortic atherosclerotic lesions. Immunization did not affect circulating cholesterol levels. Taken together our data suggest that passive immunization with anti-PC IgM significantly reduces vein graft lesion size with less inflammatory phenotype without affecting cholesterol levels, indicating an athero-protective immune response to PC. Lack of effect on established native aortic lesions may have been due to short duration of therapy and/or reduced efficacy in established lesions as compared to evolving lesions of vein graft atherosclerosis. (c) 2005 Elsevier Ireland Ltd. All rights reserved.