1992
DOI: 10.1084/jem.176.6.1703
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Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease.

Abstract: Stlmmsr~Human immunodeficiency virus (HIV) infection of brain macrophages and astroglial proliferation are central features of HIV-induced central nervous system (CNS) disorders. These observations suggest that glial cellular interactions participate in disease. In an experimental system to examine this process, we found that cocultures of HIV-infected monocytes and astroglia release high levels of cytokines and arachidonate metabolites leading to neuronotoxicity. HIV-l^D^-infected monocytes cocultured with hu… Show more

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Cited by 498 publications
(295 citation statements)
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“…Such results support a role for intercellular glial interactions in the neuropathogenesis of HAD. 9,12 Nonetheless, alternative interpretations of the data set need also be considered. For example, developmental factors could account for some of the observed differences between our microglia and MDM cultures.…”
Section: Discussionmentioning
confidence: 99%
“…Such results support a role for intercellular glial interactions in the neuropathogenesis of HAD. 9,12 Nonetheless, alternative interpretations of the data set need also be considered. For example, developmental factors could account for some of the observed differences between our microglia and MDM cultures.…”
Section: Discussionmentioning
confidence: 99%
“…Nonetheless, cysteine emanates in large excess from immune-activated, uninfected macrophages, and may thus represent a major contributor to neuronal damage. This finding represents a completely new concept in the pathogenesis of HAD, as heretofore HIV-infected macrophages had been primarily studied for their production of putative neurotoxins (7,8,20,21,34,45). Importantly, since perhaps only 10 -15% of macrophages in AIDS brains are infected whereas the remainder may be immune activated (11), this new class of toxins from non-HIV-infected, immune-stimulated macrophages may possibly represent the predominant and more widespread mode of neuronal injury.…”
Section: Discussionmentioning
confidence: 91%
“…Improper regulation of these factors can lead to impaired cellular functioning, modified neurotransmitter action, amplified inflammation and neuronal damage. Various potential neurotoxins are generated and released during the inflammatory process including reactive oxygen species, tumor necrosis factor-α (TNF-α), arachidonic acid, platelet-activating factor (PAF), nitric oxide, quinolinic acid, and glutamate (20,30,(46)(47)(48)(49)(50)(51)(52).…”
Section: Macrophage Driven Pathogenesismentioning
confidence: 99%
“…Further, G-protein linked mGlu receptors may cause increased intracellular Ca 2+ , leading to glutamate release from astrocytes (150). Astrocytic release of glutamate has been shown to be stimulated by arachidonic acid, TNF-α, and CXCL12 (50,148,151). In addition, numerous studies have indicated a potential for the reversal of glutamate uptake, causing further glutamate dumping (152,153).…”
Section: Impairment Of Astrocytes In Hadmentioning
confidence: 99%