过继负载HSP60的致耐受性DC对小鼠血管内皮功能的影响  

Recovery of endothelial dysfunction with tolerogenic dendritic cell loaded with heat shock protein 60 in apolipoprotein E-null mice

作　　者：李大主[1] 吴伟[1] 周游[1] 杨克平[1] 胡英峰[1] 曾秋棠[1] 

机构地区：[1]华中科技大学同济医学院协和医院心内科,湖北武汉430022

出　　处：《中国病理生理杂志》2006年第10期1949-1951,共3页Chinese Journal of Pathophysiology

基　　金：湖北省卫生厅科研基金资助项目(NX200511)

摘　　要：目的:探讨负载热休克蛋白60(HSP60)的致耐受性树突状细胞(DC)接种对apoE-nu ll小鼠血管内皮功能的影响。方法:分离apoE-nu ll小鼠骨髓DC,分别用HSP60和HSP60加雷帕霉素处理DC,分别获得负载HSP60 DC(DChsp)和致耐受DC(DChsp+r)。体外检测各组DC的功能。分别用DChsp、DChsp+r和盐水经静脉接种高脂饲养apoE-nu ll小鼠,共两次;设C57BL/6小鼠为未接种正常对照。末次接种后两周检测T细胞对HSP60的反应和主动脉环的内皮依赖性舒张功能。结果:体外HSP60可促进DC表达CD86及刺激淋巴细胞增殖,而致耐受DC其CD86表达显著下降。接种小鼠后,DChsp促进炎性反应,加重内皮舒张功能障碍;而DChsp+r明显抑制炎性反应,增强内皮舒张功能。结论:热休克蛋白60致耐受性树突状细胞接种可抑制HSP60特异性免疫应答,增强血管内皮舒张功能。AIM： To examine whether tolerogenic dendritic cells （DC） loaded with heat shock protein 60 （HSP60） could restore endothelial function in hypercholesterolemic apolipoprotein E （apoE） -null mice. METHODS： Bone marrow derived DC of the mice was loaded with HSP60 and co - cultured with rapamycin to generate tolerogenic DC. The tolerogenic DC, DC loaded only with HSP60 （DChsp） and saline were injected into the apoE - null mice at 6 weeks of age for two times at a one -week interval. C57BL/6 mice at the same age were taken as normal control two weeks after the last injection. Aorta was harvested for ex vivo vascular ring tension test. Immune parameters were also analyzed in vitro and in vivo. RESULTS： Compared with the non loaded DC, HSP60 pulsed DC expressed higher levels of CD86, and stimulated T lymphocytes to proliferation significantly, while the tolerogenic DC expressed lower levels of CD86, and inhibited T lymphocytes to proliferation, After immunization with different injection, Ach - induced relaxation was reduced significantly in DChsp group compared with saline group （ P 〈 0.01 ）. Treatment of mice with tolerogenic DC restored endothelium - dependent dilation in a dose - dependent manner （P 〈 0, 01 ）. The improvement in endothelial function was associated with a reduction in T cell response to HSP60. CONCLUSION： Our results indicate a rapid improvement in endothelial function with HSP60 tolerogenic DC immunization, and suggest that this immune therapy has significant vasculoprotective effects.

关 键 词：热休克蛋白质类 树突细胞 疫苗 免疫法 内皮 血管 

分 类 号：R363[医药卫生—病理学]