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 intermediates, macrophages may play an important role in neurotoxicity. In the present study we have investigated whether macrophage-derived molecules also impair 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)-beta 1, as well as leukotriene (LT) B4 and C4, prostaglandin (PG) E2 and nitric oxide radicals had no effect on the uptake of [3H]glutamate by murine astrocytes in culture. In contrast, exposure of astrocytes to the enzyme glucose oxidase (100-200 mU ml-1), which maintains steady-state levels of hydrogen peroxide, reduced glutamate uptake by 30-50%. By their dual effect, comprising secretion of glutamate and inhibition of its detoxification by astrocytes, activated macrophages and microglial cells may contribute to exacerbate excitotoxic mechanisms in neurological diseases.
Piani
D
D
Section of Clinical Immunology, University Hospital, Zürich, Switzerland.
Frei
K
K
Pfister
H W
HW
Fontana
A
A
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D015289:Leukotrienes / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D010972:Platelet Activating Factor / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000494:pharmacology*
D016207:Cytokines; D005971:Glutamates; D015289:Leukotrienes; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D018698:Glutamic Acid