PMID- 10805378
OWN - NLM
STAT- MEDLINE
DCOM- 20000822
LR  - 20131121
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 20
IP  - 4
DP  - 2000 Apr
TI  - Localization and post-Golgi trafficking of tumor necrosis factor-alpha in 
      macrophages.
PG  - 427-38
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine secreted by 
      activated macrophages. In this study, we examined the intracellular distribution 
      and trafficking of TNF-alpha. Immunofluorescence and immunogold localization 
      demonstrated that in lipopolysaccharide (LPS)-stimulated RAW264 macrophages, the 
      greatest concentration of TNF-alpha is found in the perinuclear Golgi complex. 
      Staining of the Golgi complex appeared 20 min after activation of cells and 
      persisted for 2-12 h, and TNF-alpha appeared on the cell surface only transiently 
      during this time. The rate of disappearance of Golgi staining correlated with the 
      release of the cleaved, mature TNF-alpha into the medium. Pulse chase labeling 
      and subcellular fractionation studies indicated that both 26-kDa and 17-kDa forms 
      of TNF-alpha may be present at the level of the Golgi complex. Post-Golgi 
      trafficking of TNF-alpha was modulated by agents that disrupt the cytoskeleton. 
      Interferon-gamma (IFN-gamma), which primes macrophages for TNF-alpha-dependent 
      cellular cytotoxicity, potentiated the effect of LPS by sustaining enhanced 
      intracellular pools of TNF-alpha and also promoted redistribution of TNF-alpha 
      into post-Golgi vesicular compartments. We propose that the primary pool of 
      biologically active TNF-alpha in activated macrophages is held in the Golgi 
      complex and that the cytokine is recruited directly from this intracellular pool 
      for release in response to tumor cells or pathogens.
FAU - Shurety, W
AU  - Shurety W
AD  - The Centre for Molecular and Cellular Biology, The University of Queensland, 
      Brisbane, Australia.
FAU - Merino-Trigo, A
AU  - Merino-Trigo A
FAU - Brown, D
AU  - Brown D
FAU - Hume, D A
AU  - Hume DA
FAU - Stow, J L
AU  - Stow JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 20350-15-6 (Brefeldin A)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 98600C0908 (Cycloheximide)
SB  - IM
MH  - Animals
MH  - Brefeldin A/pharmacology
MH  - Cell Line
MH  - Cell Membrane/immunology/metabolism
MH  - Cycloheximide/pharmacology
MH  - Cytoskeleton/physiology
MH  - Golgi Apparatus/drug effects/*immunology/*metabolism
MH  - Interferon-gamma/metabolism/pharmacology
MH  - Macrophages/drug effects/*immunology/*metabolism
MH  - Mice
MH  - Protein Processing, Post-Translational/immunology
MH  - Tumor Necrosis Factor-alpha/*immunology/*metabolism
EDAT- 2000/05/11 09:00
MHDA- 2000/08/29 11:01
CRDT- 2000/05/11 09:00
PHST- 2000/05/11 09:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 2000/05/11 09:00 [entrez]
AID - 10.1089/107999000312379 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2000 Apr;20(4):427-38. doi: 10.1089/107999000312379.