Neuronal fractalkine expression in HIV-1 encephalitis: Roles for macrophage recruitment and neuroprotection in the central nervous system

Ning Tong, Seth W. Perry, Qing Zhang, Harold J. James, Huang Guo, Andrew Brooks, Harshawardhan Bal, Sandra A. Kinnear, Steven Fine, Leon G. Epstein, Daniel Dairaghi, Thomas J. Schall, Howard Eliot Gendelman, Stephen Dewhurst, Leroy R. Sharer, Harris A. Gelbard

Research output: Contribution to journalArticle

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Abstract

HIV-1 infection of the brain results in chronic inflammation, contributing to the neuropathogenesis of HIV-1 associated neurologic disease. HIV-1-infected mononuclear phagocytes (MP) present in inflammatory infiltrates produce neurotoxins that mediate inflammation, dysfunction, and neuronal apoptosis. Neurologic disease is correlated with the relative number of MP in and around inflammatory infiltrates and not viral burden. It is unclear whether these cells also play a neuroprotective role. We show that the chemokine, fractalkine (FKN), is markedly up-regulated in neurons and neuropil in brain tissue from pediatric patients with HIV-1 encephalitis (HIVE) compared with those without HIVE, or that were HIV-1 seronegative. FKN receptors are expressed on both neurons and microglia in patients with HIVE. These receptors are localized to cytoplasmic structures which are characterized by a vesicular appearance in neurons which may he in cell-to- cell contact with MPs. FKN colocalizes with glutamate in these neurons. Similar findings are observed in brain tissue from an adult patient with HIVE. FKN is able to potently induce the migration of primary human monocytes across an endothelial cell/primary human fetal astrocyte trans-well bilayer, and is neuroprotective to cultured neurons when coadministered with either the HIV-1 neurotoxin platelet activating factor (PAF) or the regulatory HIV-1 gene product Tat. Thus focal inflammation in brain tissue with HIVE may up- regulate neuronal FKN levels, which in turn may he a neuroimmune modulator recruiting peripheral macrophages into the brain, and in a paracrine fashion protecting glutamatergic neurons.

Original languageEnglish (US)
Pages (from-to)1333-1339
Number of pages7
JournalJournal of Immunology
Volume164
Issue number3
DOIs
StatePublished - Feb 1 2000

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Chemokine CX3CL1
Encephalitis
HIV-1
Central Nervous System
Macrophages
Neurons
Neurotoxins
Brain
Phagocytes
Nervous System Diseases
Neuroprotection
Cytoplasmic Structures
Inflammation
Human Immunodeficiency Virus Proteins
Neuropil
Platelet Activating Factor
Microglia
Viral Load
Chemokines
Astrocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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Neuronal fractalkine expression in HIV-1 encephalitis : Roles for macrophage recruitment and neuroprotection in the central nervous system. / Tong, Ning; Perry, Seth W.; Zhang, Qing; James, Harold J.; Guo, Huang; Brooks, Andrew; Bal, Harshawardhan; Kinnear, Sandra A.; Fine, Steven; Epstein, Leon G.; Dairaghi, Daniel; Schall, Thomas J.; Gendelman, Howard Eliot; Dewhurst, Stephen; Sharer, Leroy R.; Gelbard, Harris A.

In: Journal of Immunology, Vol. 164, No. 3, 01.02.2000, p. 1333-1339.

Research output: Contribution to journalArticle

Tong, N, Perry, SW, Zhang, Q, James, HJ, Guo, H, Brooks, A, Bal, H, Kinnear, SA, Fine, S, Epstein, LG, Dairaghi, D, Schall, TJ, Gendelman, HE, Dewhurst, S, Sharer, LR & Gelbard, HA 2000, 'Neuronal fractalkine expression in HIV-1 encephalitis: Roles for macrophage recruitment and neuroprotection in the central nervous system', Journal of Immunology, vol. 164, no. 3, pp. 1333-1339. https://doi.org/10.4049/jimmunol.164.3.1333
Tong, Ning ; Perry, Seth W. ; Zhang, Qing ; James, Harold J. ; Guo, Huang ; Brooks, Andrew ; Bal, Harshawardhan ; Kinnear, Sandra A. ; Fine, Steven ; Epstein, Leon G. ; Dairaghi, Daniel ; Schall, Thomas J. ; Gendelman, Howard Eliot ; Dewhurst, Stephen ; Sharer, Leroy R. ; Gelbard, Harris A. / Neuronal fractalkine expression in HIV-1 encephalitis : Roles for macrophage recruitment and neuroprotection in the central nervous system. In: Journal of Immunology. 2000 ; Vol. 164, No. 3. pp. 1333-1339.
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AU - Brooks, Andrew

AU - Bal, Harshawardhan

AU - Kinnear, Sandra A.

AU - Fine, Steven

AU - Epstein, Leon G.

AU - Dairaghi, Daniel

AU - Schall, Thomas J.

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