Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1-infected macrophages.
We sought to identify neurotoxin(s) secreted by HIV-1-infected mononuclear phagocytes that could contribute to the pathophysiology of HIV-1-associated dementia (HAD). Neurotoxic factors were characterized in batches of conditioned media (CM) from human monocyte-derived macrophages (MDM) infected with HIV-1(ADA) and/or activated with lipopolysaccharide (LPS). All of the neurotoxicity was: present in the <3000-Da fraction; blocked by 5 microM MK801; and not trypsin sensitive or extractable into polar organic solvents. Glutamate measured in CM accounted for all neurotoxic effects observed from HIV/LPS CM in astrocyte-poor neuronal cultures and may contribute to the pathophysiology of HIV-1-associated dementia.
Jiang
Z G
ZG
Laboratory of Neurotoxicology, NIMH, 10 Center Drive, Room 3D42, NIH, 20892-1262, Bethesda, MD, USA.
Piggee
C
C
Heyes
M P
MP
Murphy
C
C
Quearry
B
B
Bauer
M
M
Zheng
J
J
Gendelman
H E
HE
Markey
S P
SP
D015526:AIDS Dementia Complex / Q000209:etiology*; D000818:Animals; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000633:toxicity*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D014357:Trypsin / Q000494:pharmacology
D008070:Lipopolysaccharides; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D014357:Trypsin