Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 366, Issue 2, Pages 579-584Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2007.12.011
Keywords
cytokine receptors; cell surface receptors; human; cytokines; inflammation; TNF receptors; exosomes; exosome-like vesicles; human plasma
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Funding
- Intramural NIH HHS [Z01 HL002544-09] Funding Source: Medline
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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.
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