Correlative transmission and scanning electron microscopy study of microglia activated by interferon-,y and tumor necrosis factor-cx in vitro

Microglia, in response to cytokines, demonstrate a number o f enhanced biochemical and functional properties which reflect a state o f activation. In this study, we evaluated the ultrastructural alterations o f murine microglia that were associated with activation by interferon-gamma (IFN-y) plus tumor necrosis factor-alpha (TNF-a). Microglial cell culture treated with these cytokines generated significant amounts o f the free radical nitric oxide (NO), a biochemical marker o f activation. Correlative transmission (TEM) and scanning (SEM) electron microscopic analyses o f these cytokine-activated microglia demonstrated two prominent features: proliferation o f cell processes and increased formation o f membrane bound dense bodies typical o f lysosomes. Since activated microglia have been implicated in the pathogenesis o f a number o f neurodegenerative diseases, application o f the ultrastructural findings in the in vitro study may prove useful in determining the state o f activation o f microglia in brain specimens from patients with these neurological disorders.