A novel atherogenic epitope from Mycobacterium tuberculosis heat shock protein 65 enhances atherosclerosis in rabbit and LDL receptor-deficient mice
A novel atherogenic epitope from Mycobacterium tuberculosis heat shock protein 65 enhances atherosclerosis in rabbit and LDL receptor-deficient mice
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结核分枝杆菌热休克蛋白 65 的新型致动脉粥样硬化表位可增强兔和 LDL 受体缺陷小鼠的动脉粥样硬化
DOI：
10.1007/s00380-011-0183-8
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
刘景晶
中科院分区：
文献类型：
--
作者：
刘景晶
既往研究证实结核分枝杆菌热休克蛋白65 （mHSP65）作为自身免疫因子在免疫相关疾病中发挥重要作用。一些重叠的mHSP65表位可能作为动脉粥样硬化和其他自身免疫相关疾病的启动因子。在本研究中，与pbs免疫或bsa免疫的兔子相比，mHSP65（91-105）免疫的高胆固醇饮食（HCD）喂养的新西兰大白兔动脉粥样硬化明显增强。用mHSP65（91-105）免疫野生型C57BL/6J小鼠可诱导主动脉内皮损伤。尽管western blot证实mHSP65（91-105）特异性抗体可以与重组人热休克蛋白60交叉反应，但mHSP65（91-105）特异性抗体对体外HUVECs没有直接作用。激光扫描共聚焦显微镜显示，mHSP65（91-105）定位于HUVECs的细胞质中，即使HUVECs在42°c下被热休克，mHSP65（91-105）特异性脾细胞也比对照分泌更多的IFN-γ。此外，过继转移mHSP65（91-105）特异性脾细胞可加速ldlr（-/-）小鼠的动脉粥样硬化。我们可以得出结论，在动物模型中，mHSP65（91-105）的（自身）免疫反应加速了动脉粥样硬化，而Th1的反应在这一过程中发挥了重要作用。
Previous studies have established that Mycobacterium tuberculosis heat shock protein 65 (mHSP65) plays an important role in immune-associated diseases as an autoimmune factor. Some overlapping epitopes of mHSP65 may serve as initiators of both atherosclerosis and other autoimmune-associated diseases. In the present study, atherosclerosis was significantly enhanced in high-cholesterol diet (HCD)-fed New Zealand white rabbits immunized with mHSP65(91-105) compared with PBS-immunized or BSA-immunized rabbits. Immunizing wild-type C57BL/6J mice with mHSP65(91-105) induced the aortic endothelial injury. Although western blot demonstrated that specific antibodies against mHSP65(91-105) can cross-react with recombinant human heat shock protein 60, specific antibodies against mHSP65(91-105) had no direct effects on HUVECs in vitro. Laser scanning confocal microscopy showed that mHSP65(91-105) localized in the cytoplasm of HUVECs, even when HUVECs were heat shocked at 42°C. mHSP65(91-105)-specific splenic cells secreted more IFN-γ than controls. Also, adoptive transfer of mHSP65(91-105)-specific splenic cells can accelerate atherosclerosis in ldlr( -/- ) mice. We can conclude that the (auto)immune response to mHSP65(91-105) accelerates atherosclerosis in animal models, and that the response of Th1 plays an important role in this progress.
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影响因子：
--
作者：
M. Reichlin
通讯作者：
M. Reichlin
影响因子：
15.3
作者：
Moudgil, K D;Chang, T T;Eradat, H;Chen, A M;Gupta, R S;Brahn, E;Sercarz, E E
通讯作者：
Sercarz, E E
影响因子：
5.5
作者：
Julie M. Williams;R. Colman;C. Brookes;C. O. Savage;Lorraine Harper
通讯作者：
Julie M. Williams;R. Colman;C. Brookes;C. O. Savage;Lorraine Harper
影响因子：
4.6
作者：
A. Hasan;T. Shinnick;Y. Mizushima;R. Zee;T. Lehner
通讯作者：
A. Hasan;T. Shinnick;Y. Mizushima;R. Zee;T. Lehner
影响因子：
6.5
作者：
Mallat, Ziad;Taleb, Soraya;Tedgui, Alain
通讯作者：
Tedgui, Alain