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Quinolinic acid is produced by macrophages stimulated by platelet activating factor, Nef and Tat

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Abstract

Activated macrophages produce quinolinic acid (QUIN), a neurotoxin, in several inflammatory brain diseases including AIDS dementia complex. We hypothesized that TL1-β, IL6, transforming growth factor (TGF-β2) and platelet activating factor could increase macrophage QUIN production. And that the HIV-1 proteins Nef, Tat and gp41 may also increase synthesis of QUIN by macrophages. At72 h there were significant increasesin QUIN production in the cells stimulated with PAF (914 ± 50 nM) and Nef (2781 ± 162 nM), with somewhat less production by Tat stimulation (645 ± 240 nM). The increases in QUIN production approximated in vitro concentrations of QUIN shown to be neurotoxic and correlated closely with indoleamine 2,3-dioxygenase induction. IL1-β, IL6, TGF-β2 and gp41 stimulation produced no significant increase in QUIN production. These results suggest that some of the neurotoxicity of PAF, nef and tat may be mediated by QUIN.

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Authors and Affiliations

  1. Centre for Immunology, St. Vincent’s Hospital, 2010, Darlinghurst, NSW, Australia

    Danielle G. Smith, Gilles J. Guillemin, Louise Pemberton, Stephen Kerr & Bruce J. Brew

  2. Department of Neurology, University of Kentucky, Lexington, KY, USA

    Avindra Nath

  3. Ray Williams Biomedical Mass Spectrometry Facility, University of New South Wales, 2052, Sydney, Australia

    George A. Smythe

  4. National Centre in HIV Epidemiology and Clinical Research, 2010, Darlinghurst, NSW, Australia

    Bruce J. Brew

  5. Department of HIV, St. Vincent’s Hospital, 2010, Darlinghurst, NSW, Australia

    Bruce J. Brew

  6. Department of Neurology, St. Vincent’s Hospital, 2010, Darlinghurst, NSW, Australia

    Bruce J. Brew

Authors
  1. Danielle G. Smith
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  2. Gilles J. Guillemin
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  3. Louise Pemberton
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  4. Stephen Kerr
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  5. Avindra Nath
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  6. George A. Smythe
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  7. Bruce J. Brew
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Smith, D.G., Guillemin, G.J., Pemberton, L. et al. Quinolinic acid is produced by macrophages stimulated by platelet activating factor, Nef and Tat. Journal of NeuroVirology 7, 56–60 (2001). https://doi.org/10.1080/135502801300069692

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  • DOI: https://doi.org/10.1080/135502801300069692

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