Correlative transmission and scanning electron microscopy study of microglia activated by interferon-gamma and tumor necrosis factor-alpha in vitro.
Microglia, in response to cytokines, demonstrate a number of enhanced biochemical and functional properties which reflect a state of activation. In this study, we evaluated the ultrastructural alterations of murine microglia that were associated with activation by interferon-gamma (IFN-gamma) plus tumor necrosis factor-alpha (TNF-alpha). Microglial cell culture treated with these cytokines generated significant amounts of the free radical nitric oxide (NO), a biochemical marker of activation. Correlative transmission (TEM) and scanning (SEM) electron microscopic analyses of these cytokine-activated microglia demonstrated two prominent features: proliferation of cell processes and increased formation of membrane bound dense bodies typical of lysosomes. Since activated microglia have been implicated in the pathogenesis of a number of neurodegenerative diseases, application of the ultrastructural findings in the in vitro study may prove useful in determining the state of activation of microglia in brain specimens from patients with these neurological disorders.
Anderson
W R
WR
Department of Pathology, University of Minnesota, Minneapolis, USA.
Martella
A
A
Drake
Z M
ZM
Hu
S
S
Peterson
P K
PK
Chao
C C
CC
D000818:Animals; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum; D005609:Free Radicals; D006056:Golgi Apparatus / Q000648:ultrastructure; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008928:Mitochondria / Q000648:ultrastructure; D009569:Nitric Oxide / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005609:Free Radicals; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma