Activation of nuclear factor kappa B in brains from children with HIV-1 encephalitis.
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.
Dollard
S C
SC
Department of Microbiology and Immunology, University of Rochester Medical Centre, NY 14642, USA.
James
H J
HJ
Sharer
L R
LR
Epstein
L G
LG
Gelbard
H A
HA
Dewhurst
S
S
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D001344:Autopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016655:HIV Core Protein p24 / Q000032:analysis; D018023:HIV Seronegativity; D015497:HIV-1; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008264:Macrophages / Q000473:pathology; D008297:Male; D017628:Microglia / Q000473:pathology; D016328:NF-kappa B / Q000032:analysis* / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D011699:Putamen / Q000473:pathology
D016655:HIV Core Protein p24; D016328:NF-kappa B