TY - JOUR
T1 - Activation of NR1a/NR2B receptors by monocyte-derived macrophage secretory products
T2 - Implications for human immunodeficiency virus type one-associated dementia
AU - Xiong, Huangui
AU - McCabe, Laura
AU - Skifter, Donald
AU - Monaghan, Daniel T.
AU - Gendelman, Howard E.
PY - 2003/5/8
Y1 - 2003/5/8
N2 - The final pathways for neuronal injury in human immunodeficiency virus type one (HIV-1)-associated dementia (HAD) were investigated in Xenopus oocytes expressing recombinant NR1a/NR2B N-methyl-D-aspartate (NMDA) receptors exposed to secretory products from HIV-infected macrophages. Pressure ejection of HIV-1-infected and CD40 ligand-stimulated human monocyte-derived macrophage (MDM) fluids produced inward currents in oocytes expressing NR1a/NR2B (30.2±5.1 nA, n=42, mean±SE), but not in uninjected cells. In contrast, control (uninfected MDM) fluids induced currents of 4.5±0.5 nA (n=17). Infected or stimulated MDM without virus showed intermediate responses. The induced currents were MDM fluid dose-dependant and blocked by the NMDA receptor antagonist 2-amino-5-phosphnovalerate (50 μM), but not by 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM). Although low levels of glutamate were detected in the culture fluids, the addition of L-glutamate decarboxylase to the MDM did not significantly change the level of induced inward currents. Our experiments demonstrate that secretory factors from HIV-1-infected MDM activate NMDA receptors NR1a/NR2B and may contribute to neuronal demise during HAD.
AB - The final pathways for neuronal injury in human immunodeficiency virus type one (HIV-1)-associated dementia (HAD) were investigated in Xenopus oocytes expressing recombinant NR1a/NR2B N-methyl-D-aspartate (NMDA) receptors exposed to secretory products from HIV-infected macrophages. Pressure ejection of HIV-1-infected and CD40 ligand-stimulated human monocyte-derived macrophage (MDM) fluids produced inward currents in oocytes expressing NR1a/NR2B (30.2±5.1 nA, n=42, mean±SE), but not in uninjected cells. In contrast, control (uninfected MDM) fluids induced currents of 4.5±0.5 nA (n=17). Infected or stimulated MDM without virus showed intermediate responses. The induced currents were MDM fluid dose-dependant and blocked by the NMDA receptor antagonist 2-amino-5-phosphnovalerate (50 μM), but not by 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM). Although low levels of glutamate were detected in the culture fluids, the addition of L-glutamate decarboxylase to the MDM did not significantly change the level of induced inward currents. Our experiments demonstrate that secretory factors from HIV-1-infected MDM activate NMDA receptors NR1a/NR2B and may contribute to neuronal demise during HAD.
KW - Human immunodeficiency virus
KW - Macrophages
KW - N-methyl-D-aspartate receptor
KW - Voltage clamp
KW - Xenopus oocytes
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U2 - 10.1016/S0304-3940(03)00194-0
DO - 10.1016/S0304-3940(03)00194-0
M3 - Article
C2 - 12697294
AN - SCOPUS:0037426561
VL - 341
SP - 246
EP - 250
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 3
ER -