ArticleProceedings of the National Academy of Sciences of the United States of America1999
Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 242 papers.
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Who cites it
242 citing papers in PubMed, 514 citations in OpenAlex.
- Characterization of platelet-monocyte complexes in HIV-1-infected individuals: possible role in HIV-associated neuroinflammation.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Neuroinflammation and NeuroHIV: understanding the role of HIV-1 related factors in microglial activation.Translational psychiatry · 2026Review
- HIV gp120 induces TREM1 expression through TLR-PGE₂ signalling in human monocyte-derived microglia.Journal of neuroinflammation · 2026Article
- CCL5 paradoxically regulates glomerular injury by skewing macrophage polarization.JCI insight · 2025Article
- Viruses and the Brain-A Relationship Prone to Trouble.Viruses · 2025Review
- Transformation of brain myeloid cell populations by SIV in rhesus macaques revealed by multiomics.Communications biology · 2025Article
- Cannabis use is associated with alterations in NLRP3 inflammasome related gene expression in monocyte-derived macrophages from people living with HIV.Frontiers in immunology · 2025Article
- Transformation of brain myeloid cell populations by SIV in rhesus macaques revealed by multiomics.Research square · 2024Article
- Modeling HIV-1 infection and NeuroHIV in hiPSCs-derived cerebral organoid cultures.Journal of neurovirology · 2024Article
- Interferon-β deficiency alters brain response to chronic HIV-1 envelope protein exposure in a transgenic model of NeuroHIV.Brain, behavior, and immunity · 2024Article
- A critical role for Macrophage-derived Cysteinyl-Leukotrienes in HIV-1 induced neuronal injury.Brain, behavior, and immunity · 2024Article
- HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology.International journal of molecular sciences · 2024Review
- Antiretroviral drugs from multiple classes induce loss of excitatory synapses between hippocampal neurons in culture.Frontiers in pharmacology · 2024Article
- Review
- Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy.Science advances · 2022Article
- HIV-Proteins-Associated CNS Neurotoxicity, Their Mediators, and Alternative Treatments.Cellular and molecular neurobiology · 2022Review
- Article
- HIV and FIV glycoproteins increase cellular tau pathology via cGMP-dependent kinase II activation.Journal of cell science · 2022Article
- Recent Advances in the Molecular and Cellular Mechanisms of gp120-Mediated Neurotoxicity.Cells · 2022Review
- Review
182 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
HIV-1 glycoprotein gp120 induces injury and apoptosis in rodent and human neurons in vitro and in vivo and is therefore thought to contribute to HIV-associated dementia. In addition to CD4, different gp120 isolates bind to the alpha- or beta-chemokine receptors CXCR4 and CCR5, respectively. These and other chemokine receptors are on brain macrophages/microglia, astrocytes, and neurons. Thus, apoptosis could occur via direct interaction of gp120 with neurons, indirectly via stimulation of glia to release neurotoxic factors, or via both pathways. Here we show in rat cerebrocortical cultures that recapitulate the type and proportion of cells normally found in brain, i.e., neurons, astrocytes, and macrophages/microglia, that the beta-chemokines RANTES (regulated on activation, normal T cell expressed and secreted) and macrophage inflammatory protein (MIP-1beta) protect neurons from gp120SF2-induced apoptosis. The gp120SF2 isolate prefers binding to CXCR4 receptors, similar to the physiological alpha-chemokine ligands, stromal cell-derived factor (SDF)-1alpha/beta. SDF-1alpha/beta failed to prevent gp120SF2 neurotoxicity, and in fact also induced neuronal apoptosis. We could completely abrogate gp120SF2-induced neuronal apoptosis with the tripeptide TKP, which inhibits activation of macrophages/microglia. In contrast, TKP or depletion of macrophages/microglia did not prevent SDF-1 neurotoxicity. Inhibition of p38 mitogen-activated protein kinase ameliorated both gp120SF2- and SDF-1-induced neuronal apoptosis. Taken together, these results suggest that gp120SF2 and SDF-1 differ in the cell type on which they stimulate CXCR4 to induce neuronal apoptosis, but both ligands use the p38 mitogen-activated protein kinase pathway for death signaling. Moreover, gp120SF2-induced neuronal apoptosis depends predominantly on an indirect pathway via activation of chemokine receptors on macrophages/microglia, whereas SDF-1 may act directly on neurons or astrocytes.
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