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Increased quinolinate immunoreactivity in the peripheral blood monocytes/macrophages from SIV-infected monkeys
A M Namboodiri1, C N Venkateshan, R Narayanan
1Department of Biology, Georgetown University, Washington DC 20057, USA.
Abstract:
Quinolinate (QUIN), a metabolite in the kynurenine pathway of tryptophan degradation and a neurotoxin that is thought to act through the NMDA receptor system, was localized in cultured peripheral blood monocytes/macrophages from SIV-infected monkeys using a recently developed immunohistochemical method. Significant increases in QUIN immunoreactive (IR) cells were detected in all five SIV-infected monkeys examined. Multinucleated giant cells, a hallmark of lentiviral infection, were visible in selected samples. Treatment with the QUIN precursors, tryptophan and kynurenine, increased the number of QUIN-IR cells in both the control and SIV-infected preparations, perhaps by a mass action mechanism. We hypothesize that in SIV-infected monkeys, infiltrating monocytes/macrophages contribute to the high level of brain QUIN and associated neuropathology.
Insights
Quinolinate (QUIN), a neurotoxin, increased in monocytes/macrophages of SIV-infected monkeys. This suggests these cells may contribute to SIV-related brain damage.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Quinolinate (QUIN) is a neurotoxin and metabolite in the kynurenine pathway.
- QUIN is implicated in NMDA receptor system-mediated neurotoxicity.
- Monocytes/macrophages play roles in immune responses and neuroinflammation.
Purpose of the Study:
- To investigate the presence and localization of QUIN in monocytes/macrophages from SIV-infected monkeys.
- To determine if SIV infection alters QUIN levels in these immune cells.
- To explore the potential contribution of QUIN-producing monocytes/macrophages to SIV neuropathology.
Main Methods:
- Immunohistochemical localization of QUIN in cultured peripheral blood monocytes/macrophages.
- Analysis of SIV-infected monkey samples.
- Treatment with QUIN precursors (tryptophan, kynurenine) to assess their effect on QUIN levels.
Main Results:
- Significant increases in QUIN immunoreactive (IR) cells were observed in all SIV-infected monkeys.
- Multinucleated giant cells, indicative of lentiviral infection, were present.
- Administration of tryptophan and kynurenine increased QUIN-IR cells in both control and SIV-infected groups.
Conclusions:
- Monocytes/macrophages in SIV-infected monkeys exhibit elevated levels of the neurotoxin QUIN.
- These findings support the hypothesis that infiltrating monocytes/macrophages contribute to high brain QUIN levels and neuropathology in SIV infection.
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