Activation of NR1a/NR2B receptors by monocyte-derived macrophage secretory products

Implications for human immunodeficiency virus type one-associated dementia

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)246-250
Number of pages5
JournalNeuroscience Letters
Volume341
Issue number3
DOIs
StatePublished - May 8 2003

Fingerprint

Dementia
Macrophages
HIV
HIV-1
Oocytes
Glutamic Acid
6-Cyano-7-nitroquinoxaline-2,3-dione
CD40 Ligand
Glutamate Decarboxylase
Xenopus
N-Methyl-D-Aspartate Receptors
Viruses
Pressure
Wounds and Injuries

Keywords

  • Human immunodeficiency virus
  • Macrophages
  • N-methyl-D-aspartate receptor
  • Voltage clamp
  • Xenopus oocytes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Activation of NR1a/NR2B receptors by monocyte-derived macrophage secretory products: Implications for human immunodeficiency virus type one-associated dementia",
abstract = "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.",
keywords = "Human immunodeficiency virus, Macrophages, N-methyl-D-aspartate receptor, Voltage clamp, Xenopus oocytes",
author = "Huangui Xiong and Laura McCabe and Donald Skifter and Monaghan, {Daniel T} and Gendelman, {Howard Eliot}",
year = "2003",
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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 Eliot

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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.

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