HIV-1 infected immune competent mononuclear phagocytes influence the pathways to neuronal demise

J. Zheng, Michael R. Thylin, Yuri Persidsky, Clancy E. Williams, Robin L. Cotter, Walter Zink, Lisa Ryan, Anuja Ghorpade, Kathleen Lewis, Howard E. Gendelman

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Secretory products from HIV-1-infected immune-competent mononuclear phagocytes (MP) damage neuronal dendritic arbor (Zheng et al., 2001). The mechanism behind neuronal injury and whether it is species and/or viral strain dependent is not fully understood. To these ends, we investigated whether HIV-1-infected and lipopolysachharide (LPS)-activated MDM elicit neuronal injury in primary human neurons. Neuronal damage was compared to that seen in rat neurons. Utilizing a spectrum of HIV-1 strains to infect human monocyte-derived macrophages (MDM), productive viral replication proved necessary, but not sufficient, for neuronal injury. Neuronal demise was induced by virion-free HIV-1-infected and immune-activated MDM culture supernatants. Maximal alterations in glutamate mediated neuronal signaling, resulted from exposure to secretory products from HIV-1-infected and immune-activated MDM. Apoptosis was the predominant mechanism of cell death induced by HIV-1-infected and LPS-treated MDM. Importantly, neuronal injury and increases in calcium influx mediated by HIV-1-infected and immune-activated MDM culture supernatants was partially blocked by the N-methyl D-aspartate (NMDA) receptor antagonist, MK 801. These data support a primary role for immune-activation in MP neurotoxic activities. The upregulation of NMDA receptor sensitive soluble factors and neuronal apoptosis by HIV-1-infected and immune-activated MDM provide unique insights into links between soluble factors, produced as a consequence of MP immunity, and neuronal demise in HAD.

Original languageEnglish
Article numberBF03033204
Pages (from-to)461-484
Number of pages24
JournalNeurotoxicity Research
Volume3
Issue number5
DOIs
StatePublished - 1 Jan 2001

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    Zheng, J., Thylin, M. R., Persidsky, Y., Williams, C. E., Cotter, R. L., Zink, W., Ryan, L., Ghorpade, A., Lewis, K., & Gendelman, H. E. (2001). HIV-1 infected immune competent mononuclear phagocytes influence the pathways to neuronal demise. Neurotoxicity Research, 3(5), 461-484. [BF03033204]. https://doi.org/10.1007/BF03033204