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

Jialin C Zheng, M. R. Thylin, Y. Persidsky, C. E. Williams, R. L. Cotter, W. Zink, L. Ryan, A. Ghorpade, K. Lewis, Howard Eliot Gendelman

Research output: Contribution to journalArticle

24 Citations (Scopus)

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

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Macrophages
Phagocytes
HIV-1
N-Methyl-D-Aspartate Receptors
Cell culture
Wounds and Injuries
Neurons
Apoptosis
Dizocilpine Maleate
Cell death
Rats
Glutamic Acid
Virion
Chemical activation
Immunity
Cell Death
Up-Regulation
Calcium

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

HIV-1 infected immune competent mononuclear phagocytes influence the pathways to neuronal demise. / Zheng, Jialin C; Thylin, M. R.; Persidsky, Y.; Williams, C. E.; Cotter, R. L.; Zink, W.; Ryan, L.; Ghorpade, A.; Lewis, K.; Gendelman, Howard Eliot.

In: Neurotoxicity Research, Vol. 3, No. 5, BF03033204, 01.01.2001, p. 461-484.

Research output: Contribution to journalArticle

Zheng, JC, Thylin, MR, Persidsky, Y, Williams, CE, Cotter, RL, Zink, W, Ryan, L, Ghorpade, A, Lewis, K & Gendelman, HE 2001, 'HIV-1 infected immune competent mononuclear phagocytes influence the pathways to neuronal demise', Neurotoxicity Research, vol. 3, no. 5, BF03033204, pp. 461-484. https://doi.org/10.1007/BF03033204
Zheng, Jialin C ; Thylin, M. R. ; Persidsky, Y. ; Williams, C. E. ; Cotter, R. L. ; Zink, W. ; Ryan, L. ; Ghorpade, A. ; Lewis, K. ; Gendelman, Howard Eliot. / HIV-1 infected immune competent mononuclear phagocytes influence the pathways to neuronal demise. In: Neurotoxicity Research. 2001 ; Vol. 3, No. 5. pp. 461-484.
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