Murine brain macrophages induced NMDA receptor mediated neurotoxicity in vitro by secreting glutamate.
Supernatants (SN) of brain macrophages in culture induce death of cerebellar granule cells in vitro, while those of astrocytes and endothelial cells do not. This toxicity can be prevented by N-methyl-D-aspartate (NMDA) receptor antagonists. Macrophage SN contain high concentrations of glutamate. Reducing the glutamate level of macrophage SN, either by exposure to astrocytes or by enzymatic degradation abolished the toxic effect. Thus, macrophage neurotoxicity is mediated by glutamate acting on NMDA receptors, and might play a role in vivo in traumatic and cerebrovascular brain lesions.
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
D
D
Piani
K
K
Frei
K Q
KQ
Do
M
M
Cuénod
A
A
Fontana
D015763:2-Amino-5-phosphonovalerate / Q000633:toxicity; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000633:toxicity; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D011810:Quinoxalines / Q000633:toxicity; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D005971:Glutamates; D009498:Neurotoxins; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate