Ethanol induced changes in superoxide anion and nitric oxide in cultured microglia.
Induction of oxidative stress has been implicated as a causative factor in fetal alcohol syndrome although the source of reactive oxygen species is not clear. One potential source is the microglia, the CNS macrophage, which generate superoxide anion as part of their normal immune function. Our data indicate that chronic exposure to ethanol alters the function of cultured neonatal hamster microglia by inducing superoxide anion production in resting (nonstimulated) cells. An increase in superoxide anion was seen at 24 or 48 hr of ethanol treatment but was not seen during acute exposures of up to 3 hr. This effect was dose dependent and was maximal at 20 mM ethanol. Treatment with ethanol did not directly activate the respiratory burst seen in microglia and did not act as a priming agent to enhance phorbol-ester-stimulated superoxide anion production. Lipopolysaccharide-mediated priming of microglial superoxide anion production was also not affected by exposure to 20 mM ethanol for 24 hr. Ethanol treatment, however, did depress nitric oxide (NO) levels in hamster microglia which had been stimulated to produce NO by polyinosinic:polycytidylic acid (poly I:C). Uptake of latex beads was increased by 24 hr of exposure to ethanol. The overall action of ethanol on neonatal hamster microglia is to shift the balance between the production of superoxide anion and NO. Because NO is protective to mammalian cells, these changes predict that oxidative stress in the CNS would be enhanced.
Colton
C A
CA
Department of Physiology and Biophysics, Georgetown University Medical School, Washington, DC 20007, USA.
Snell-Callanan
J
J
Chernyshev
O N
ON
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D000431:Ethanol / Q000633:toxicity*; D017628:Microglia / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D000431:Ethanol