ACTIVATED HUMAN MICROGLIA PRODUCE THE EXCITOTOXIN QUINOLINIC ACID

WE aimed to determine the relative role of quinolinic acid synthesis i n purified human microglia, monocyte-derived macrophages and astrocyte s in the human brain following immune stimulation. Microglia and macro phages significantly increased quinolinic acid synthesis from tryptoph an following activation by either lipopolysaccharide or interferon-gam ma. Quinolinic acid synthesis by individual microglia was heterogeneou s, and its production by activated macrophages was approximately 32-fo ld greater than its microglial synthesis. Quinolinic acid synthesis by astrocytes was undetectable. Microglia may, therefore, be the primary endogenous cell type responsible for quinolinic acid synthesis in the brain parenchyma. However, under pathological conditions which precip itate blood-brain barrier compromise and/or leukocytic infiltration, i ntracerebral quinolinic acid may be derived chiefly from cells of the peripheral immune system such as activated macrophages.