Circulating TNFR1 exosome-like vesicles partition with the LDL fraction of human plasma
Circulating TNFR1 exosome-like vesicles partition with the LDL fraction of human plasma
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DOI：
10.1016/j.bbrc.2007.12.011
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发表时间：
2008-02-08
影响因子：
3.1
通讯作者：
Levine, Stewart J.
中科院分区：
文献类型：
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作者：
Zhang, Jing;Hawari, Feras I.;Levine, Stewart J.
细胞外I型肿瘤坏死因子受体(TNFR1)的产生有两种机制，即蛋白水解性切割TNFR1胞外区和释放全长的TNFR1在外切体样小泡膜上。在这里，我们评估了TNFR1外切体样囊泡是否在人类血液中循环。人血清的免疫电子显微镜显示TNFR1外切体样囊泡，直径27-36 nm，而人血浆的免疫印迹显示48 kDa的TNFR1，与膜相关受体一致。凝胶过滤层析显示，人血浆中48 kDa的TNFR1与低密度脂蛋白颗粒大小共分离，但密度独立分离，表明它们与低密度脂蛋白颗粒是不同的。此外，与来自人血管内皮细胞的55 kDa膜相关的TNFR1相比，人血浆中48 kDa外切体相关的TNFR1含有更少的N-连接碳水化合物。因此，一群不同的TNFR1外切体样囊泡在人血浆中循环，并可能调节肿瘤坏死因子介导的炎症。由爱思唯尔公司出版。
Extracellular type I tumor necrosis factor receptors (TNFR1) are generated by two mechanisms, proteolytic cleavage of TNFR1 ecto-domains and release of full-length TNFR1 in the membranes of exosome-like vesicles. Here, we assessed whether TNFR1 exosome-like vesicles circulate in human blood. Immunoelectron microscopy of human serum demonstrated TNFR1 exosome-like vesicles, with a diameter of 27 - 36 nm, while Western blots of human plasma showed a 48-kDa TNFR1, consistent with a membrane-associated receptor. Gel filtration chromatography revealed that the 48-kDa TNFR1 in human plasma co-segregated with LDL particles by size, but segregated independently by density, demonstrating that they are distinct from LDL particles. Furthermore, the 48-kDa exosome-associated TNFR1 in human plasma contained a reduced content of N-linked carbohydrates as compared to the 55-kDa membrane-associated TNFR1 from human vascular endothelial cells. Thus, a distinct population of TNFR1 exosome-like vesicles circulate in human plasma and may modulate TNF-mediated inflammation. Published by Elsevier Inc.