GLUTAMATE UPTAKE BY ASTROCYTES IS INHIBITED BY REACTIVE OXYGEN INTERMEDIATES BUT NOT BY OTHER MACROPHAGE-DERIVED MOLECULES INCLUDING CYTOKINES, LEUKOTRIENES OR PLATELET-ACTIVATING-FACTOR

By their property to release glutamate and reactive oxygen intermediat es, macrophages may play an important role in neurotoxicity. In the pr esent study we have investigated whether macrophage-derived molecules also impaire the detoxification of glutamate by astrocytes. Cytokines, including interleukin (IL)-1, 6 and 10, interferon (IFN)-alpha/beta, tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF) -beta1, as well as leukotriene (LT) B4 and C4, prostaglandin (PG) E2 a nd nitric oxide radicals had no effect on the uptake of [H-3]glutamate by murine astrocytes in culture. In contrast, exposure of astrocytes to the enzyme glucose oxidase (100-200 mU ml-1), which maintains stead y-state levels of hydrogen peroxide, reduced glutamate uptake by 30-50 %. By their dual effect, comprising secretion of glutamate and inhibit ion of its detoxification by astrocytes, activated macrophages and mic roglial cells may contribute to exacerbate excitotoxic mechanisms in n eurological diseases.