title: Circulating TNFR1 exosome-like vesicles partition with the LDL fraction of human plasma.
abstract: Extracellular type I tumor necrosis factor receptors (TNFR1) are generated by two mechanisms, proteolytic cleavage of TNFR1 ectodomains 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 27-36nm, 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.
authors: Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Jing
authors: J
authors: Zhang
authors: Feras I
authors: FI
authors: Hawari
authors: Robert D
authors: RD
authors: Shamburek
authors: Barbara
authors: B
authors: Adamik
authors: Maryann
authors: M
authors: Kaler
authors: Aminul
authors: A
authors: Islam
authors: Da-Wei
authors: DW
authors: Liao
authors: Farshid N
authors: FN
authors: Rouhani
authors: Matthew
authors: M
authors: Ingham
authors: Stewart J
authors: SJ
authors: Levine
mesh_terms: D042783:Endothelial Cells / Q000378:metabolism* / Q000648:ultrastructure*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D022161:Transport Vesicles / Q000648:ultrastructure*
chemical_list: D008077:Lipoproteins, LDL; D047888:Receptors, Tumor Necrosis Factor, Type I