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Research Article Free access | 10.1172/JCI115024
Department of Laboratory Medicine, San Francisco Veterans Administration Medical Center, California 94121.
Find articles by Pulliam, L. in: JCI | PubMed | Google Scholar
Department of Laboratory Medicine, San Francisco Veterans Administration Medical Center, California 94121.
Find articles by Herndier, B. in: JCI | PubMed | Google Scholar
Department of Laboratory Medicine, San Francisco Veterans Administration Medical Center, California 94121.
Find articles by Tang, N. in: JCI | PubMed | Google Scholar
Department of Laboratory Medicine, San Francisco Veterans Administration Medical Center, California 94121.
Find articles by McGrath, M. in: JCI | PubMed | Google Scholar
Published February 1, 1991 - More info
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.
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