Piani D, Spranger M, Frei K, Schaffner A, Fontana A.
Macrophage-induced cytotoxicity of N-methyl-D-aspartate receptor positive neurons involves excitatory amino acids rather than reactive oxygen intermediates and cytokines, Eur J Immunol 22(9), 1992 :2429-36, 1992.
Abstract
The co-localization of activated macrophages and damaged neurons observed in brain injury and degenerative brain diseases may hint to
macrophage-induced neuronal cytotoxicity. Recently, macrophages have been found to secrete neurotoxic molecules such as radical oxygen
intermediates and glutamate, the latter interacting with N-methyl-D-aspartate (NMDA) receptors. As shown in the present study, brain
macrophages termed microglial cells co-cultured with differentiated cerebellar neurons exert potent neurotoxic effects. Neurotoxicity is
unlikely to be due to cytokines since tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 and interferon
(IFN)-alpha-beta/IFN-gamma had no such effects. In contrast, when treating neurons with H2O2 or oxygen radical-generating systems
cytotoxicity was induced. Furthermore, microglia were found to produce O2- and H2O2 when triggered with phorbol 12-myristate
13-acetate.
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