Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains.
We wanted to establish an in vitro human model for AIDS-associated dementia and pursue the hypothesis that this disease process may be a result of soluble factors produced by HIV-infected macrophages. Human brain aggregates were prepared from nine different brain specimens, and were treated with supernatants from in vitro HIV-infected macrophages (SI), uninfected macrophages (SU), infected T cells, or macrophage-conditioned media from four AIDS patients. Seven of nine treated brains exposed to SI showed peripheral rarefaction after 1 wk of incubation that by ultrastructural analysis showed cytoplasmic vacuolation. Aggregates from two of three brain cultures treated with SI for 3 wk became smaller, an approximately 50% decrease in size. The degree of apparent toxicity in brains exposed to patient-derived macrophage supernatants paralleled the proportion of macrophages found to be expressing HIV p24. Ultrastructural abnormalities were not observed in brains treated with supernatants from HIV-infected T cells, uninfected macrophages, or LPS-activated macrophages. Levels of five neurotransmitter amino acids were decreased in comparison to the structural amino acid leucine. These findings suggest that HIV-infected macrophages, infected both in vitro as well as derived from AIDS patients' peripheral blood, produce factors that cause reproducible histochemical, ultrastructural, and functional abnormalities in human brain aggregates.
Pulliam
L
L
Department of Laboratory Medicine, San Francisco Veterans Administration Medical Center, California 94121.
Herndier
B G
BG
Tang
N M
NM
McGrath
M S
MS
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D002478:Cells, Cultured; D006678:HIV / Q000302:isolation & purification*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D008854:Microscopy, Electron; D009474:Neurons / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000032:analysis; D014343:Trypan Blue / Q000032:analysis
D008070:Lipopolysaccharides; D018377:Neurotransmitter Agents; D007770:L-Lactate Dehydrogenase; D014343:Trypan Blue