全长55 kDa肿瘤坏死因子受体1在外泌体样囊泡中的释放：可溶性细胞因子受体产生的一种机制。
Release of full-length 55-kDa TNF receptor 1 in exosome-like vesicles: a mechanism for generation of soluble cytokine receptors.
作者信息
Hawari Feras I, Rouhani Farshid N, Cui Xinle, Yu Zu-Xi, Buckley Caitriona, Kaler Maryann, Levine Stewart J
机构信息
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1297-302. doi: 10.1073/pnas.0307981100. Epub 2004 Jan 26.
Soluble tumor necrosis factor receptors (TNFRs) are important modulators of TNF bioactivity. Proteolytic cleavage of the 28-kDa ectodomain of TNFR1 has been recognized as the mechanism by which soluble TNFR is shed. We now describe the release of exosome-like vesicles as a mechanism for the generation of soluble, full-length 55-kDa TNFR1. We found unexpectedly that the predominant form of soluble TNFR1 in human serum and lung epithelial lining fluid is a full-length 55-kDa protein. Furthermore, supernatants from human vascular endothelial cells contain only full-length 55-kDa TNFR1 that can be sedimented by high-speed centrifugation, floated on sucrose gradients at a density of 1.1 g/ml, and associated with vesicles that range in diameter from 20 nm to 50 nm. We conclude that the release of TNFR1 exosome-like vesicles represents a previously unrecognized mechanism by which constitutive production of soluble cytokine receptors may be regulated, independent of ectodomain cleavage by receptor sheddases.
可溶性肿瘤坏死因子受体（TNFRs）是TNF生物活性的重要调节因子。TNFR1的28 kDa胞外域的蛋白水解切割已被认为是可溶性TNFR脱落的机制。我们现在描述了外泌体样囊泡的释放是产生可溶性全长55 kDa TNFR1的一种机制。我们意外地发现，人血清和肺上皮衬液中可溶性TNFR1的主要形式是全长55 kDa蛋白。此外，人血管内皮细胞的上清液仅含有全长55 kDa TNFR1，其可通过高速离心沉淀，以1.1 g/ml的密度漂浮在蔗糖梯度上，并与直径为20 nm至50 nm的囊泡相关。我们得出结论，TNFR1外泌体样囊泡的释放代表了一种以前未被认识的机制，通过该机制可溶性细胞因子受体的组成性产生可能受到调节，而与受体蛋白酶的胞外域切割无关。
Zotero 插件