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Activation of nuclear factor kappa B in brains from children with HIV-1 encephalitis.
Dollard SC; James HJ; Sharer LR; Epstein LG; Gelbard HA; Dewhurst S;
December 30, 1996
Neuropathol Appl Neurobiol. 1995 Dec;21(6):518-28. Unique Identifier :

Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system is associated with decreased neuronal density in discrete areas of the brain. Neuronal loss may occur via apoptosis, initiated by soluble neurotoxic factors secreted from HIV-1 infected macrophages and microglia. To examine further the molecular events involved in HIV-1 neuropathogenesis, we assessed the activity of NF kappa B, an inducible transcription factor involved in the activation of multiple proinflammatory, and potentially neurotoxic, genes. NF kappa B was analysed by immunocytochemistry using specific antisera to the NF kappa B p. 50 and p. 65 subunits. Brains from children with HIV-1 encephalitis and progressive encephalopathy were found to contain increased numbers of NF kappa B immunoreactive cells, relative to control brains (HIV-1 negative, or HIV-1 positive without encephalitis). Double-labelling studies using antibodies to CD68, or RCA-1 lectin, markers for cells of monocyte/macrophage lineage, revealed an increase in the number of microglia and macrophages with nuclear immunoreactivity for NF kappa B in association with HIV-1 encephalitis. NF kappa B positive multinucleated giant cells were also detected, as were cells which contained both NF kappa B and HIV-1 antigen. In contrast, the number of neurons and GFAP-positive astrocytes that were immunoreactive for NF kappa B was approximately the same in all groups of subjects. These data are consistent with the hypothesis that persistent, high-level activation of NF kappa B may promote the sustained production of neurotoxins by microglia and macrophages during HIV-1 encephalitis.

Adolescence Autopsy AIDS Dementia Complex/METABOLISM/*PATHOLOGY Brain/METABOLISM/*PATHOLOGY Child Child, Preschool Comparative Study Female Human HIV Core Protein p24/ANALYSIS HIV Seronegativity *HIV-1 Immunoenzyme Techniques Immunohistochemistry Infant Infant, Newborn Macrophages/PATHOLOGY Male Microglia/PATHOLOGY Neurons/*PATHOLOGY NF-kappa B/*ANALYSIS/METABOLISM Putamen/PATHOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE