TNFalpha trafficking in cerebral vascular endothelial cells.
Using small tags, we tracked the pathway of tumor necrosis factor (TNF)alpha across cerebral vascular endothelial cells. In cerebral microvessel derived RBE4 cells, (125)I-TNFalpha had rapid endocytosis within the first 20 min and showed substantial exocytosis in the intact form. Biotinylated TNFalpha was detected at different time points after endocytosis by streptavidin-Quantum dots which showed its time-dependent colocalization with intracellular organelles. In mice, electron microscopic autoradiography after intravenous injection of (125)I-TNFalpha showed its transcytosis, as signals emerged on the abluminal side of the endothelial cells and reached brain parenchyma. The vesicular trafficking of TNFalpha reflects the immunomodulatory potential of peripheral cytokines for the CNS.
Pan
Weihong
W
Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. weihong.pan@pbrc.edu
Kastin
Abba J
AJ
Daniel
Jeremy
J
Yu
Chuanhui
C
Baryshnikova
Larisa M
LM
von Bartheld
Christopher S
CS
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004705:Endocytosis / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D005455:Fluorescent Antibody Technique; D007457:Iodine Radioisotopes; D051379:Mice; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D021381:Protein Transport / Q000502:physiology*; D011849:Radioactive Tracers; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007457:Iodine Radioisotopes; D011849:Radioactive Tracers; D014409:Tumor Necrosis Factor-alpha