Endocytosis of uncleaved tumor necrosis factor-alpha in macrophages

Shurety, Wenda, Pagan, Julia K., Prins, Johannes B. and Stow, Jennifer L. (2001) Endocytosis of uncleaved tumor necrosis factor-alpha in macrophages. Laboratory Investigation, 81 1: 107-117. doi:10.1038/labinvest.3780216

Author Shurety, Wenda
Pagan, Julia K.
Prins, Johannes B.
Stow, Jennifer L.
Title Endocytosis of uncleaved tumor necrosis factor-alpha in macrophages
Journal name Laboratory Investigation   Check publisher's open access policy
ISSN 0023-6837
Publication date 2001-01-01
Sub-type Article (original research)
DOI 10.1038/labinvest.3780216
Volume 81
Issue 1
Start page 107
End page 117
Total pages 11
Place of publication Baltimore, MD, United States
Publisher Nature
Language eng
Abstract Activated monocytes and macrophages secrete the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) TNF-alpha is produced as a 26 kd transmembrane protein that is cleaved to release a 17 kd soluble protein. TNF-alpha in both forms is biologically active. The intracellular trafficking of membrane-associated TNF-alpha in lipopolysaccharide-activated mouse macrophages was assessed after treatment with the metalloprotease inhibitor BB-3103, which prevents the cleavage of pro-TNF-alpha. Immunoprecipitation and immunofluorescence studies showed sustained expression of cell-associated TNF-alpha in the presence of the inhibitor. Cell immunoreactivity and surface biotinylation revealed that uncleaved TNF-alpha accumulated on the cell surface and was endocytosed, appearing in intracellular vesicles. Perturbation of post-Golgi traffic blocked the surface expression of 26 kd TNF-alpha. Tracking a bolus of TNF-alpha over time in cycloheximide-treated cells confirmed that uncleaved TNF-alpha is first transported to the cell surface and subsequently endocytosed. Vesicular structures immunoreactive for TNF-alpha were identified as endosomes by double labeling. The secretory and membrane-associated endocytic trafficking of TNF-alpha provides a mechanism for modulating the quantity of biologically active 26 kd TNF-alpha expressed on macrophages, allowing regulation of paracrine and autocrine responses.
Keyword Pathology
Metalloproteinase inhibitor
Surface expression
Factor cachectin
In vitro
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Diamantina Institute - Open Access Collection
UQ Diamantina Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 29 times in Thomson Reuters Web of Science Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 02:14:45 EST