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J Clin Invest. 1991 February; 87(2): 503–512.
PMCID: PMC296337

Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains.

Abstract

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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Selected References

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  • Price RW, Brew BJ. The AIDS dementia complex. J Infect Dis. 1988 Nov;158(5):1079–1083. [PubMed]
  • Navia BA, Cho ES, Petito CK, Price RW. The AIDS dementia complex: II. Neuropathology. Ann Neurol. 1986 Jun;19(6):525–535. [PubMed]
  • Vazeux R, Brousse N, Jarry A, Henin D, Marche C, Vedrenne C, Mikol J, Wolff M, Michon C, Rozenbaum W, et al. AIDS subacute encephalitis. Identification of HIV-infected cells. Am J Pathol. 1987 Mar;126(3):403–410. [PubMed]
  • Shaw GM, Harper ME, Hahn BH, Epstein LG, Gajdusek DC, Price RW, Navia BA, Petito CK, O'Hara CJ, Groopman JE, et al. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. [PubMed]
  • Gonda MA, Wong-Staal F, Gallo RC, Clements JE, Narayan O, Gilden RV. Sequence homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science. 1985 Jan 11;227(4683):173–177. [PubMed]
  • Levy JA, Shimabukuro J, Hollander H, Mills J, Kaminsky L. Isolation of AIDS-associated retroviruses from cerebrospinal fluid and brain of patients with neurological symptoms. Lancet. 1985 Sep 14;2(8455):586–588. [PubMed]
  • Ho DD, Rota TR, Schooley RT, Kaplan JC, Allan JD, Groopman JE, Resnick L, Felsenstein D, Andrews CA, Hirsch MS. Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med. 1985 Dec 12;313(24):1493–1497. [PubMed]
  • Hollander H, Levy JA. Neurologic abnormalities and recovery of human immunodeficiency virus from cerebrospinal fluid. Ann Intern Med. 1987 May;106(5):692–695. [PubMed]
  • Cheng-Mayer C, Rutka JT, Rosenblum ML, McHugh T, Stites DP, Levy JA. Human immunodeficiency virus can productively infect cultured human glial cells. Proc Natl Acad Sci U S A. 1987 May;84(10):3526–3530. [PubMed]
  • Chiodi F, Fuerstenberg S, Gidlund M, Asjö B, Fenyö EM. Infection of brain-derived cells with the human immunodeficiency virus. J Virol. 1987 Apr;61(4):1244–1247. [PMC free article] [PubMed]
  • Brenneman DE, Westbrook GL, Fitzgerald SP, Ennist DL, Elkins KL, Ruff MR, Pert CB. Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide. Nature. 1988 Oct 13;335(6191):639–642. [PubMed]
  • Wahl LM, Corcoran ML, Pyle SW, Arthur LO, Harel-Bellan A, Farrar WL. Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1. Proc Natl Acad Sci U S A. 1989 Jan;86(2):621–625. [PubMed]
  • Gurney ME, Heinrich SP, Lee MR, Yin HS. Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science. 1986 Oct 31;234(4776):566–574. [PubMed]
  • Crowe S, Mills J, McGrath MS. Quantitative immunocytofluorographic analysis of CD4 surface antigen expression and HIV infection of human peripheral blood monocyte/macrophages. AIDS Res Hum Retroviruses. 1987 Summer;3(2):135–145. [PubMed]
  • McGrath MS, Hwang KM, Caldwell SE, Gaston I, Luk KC, Wu P, Ng VL, Crowe S, Daniels J, Marsh J, et al. GLQ223: an inhibitor of human immunodeficiency virus replication in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2844–2848. [PubMed]
  • Locksley RM, Crowe S, Sadick MD, Heinzel FP, Gardner KD, Jr, McGrath MS, Mills J. Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo. J Clin Invest. 1988 Dec;82(6):2097–2105. [PMC free article] [PubMed]
  • Pulliam L, Berens ME, Rosenblum ML. A normal human brain cell aggregate model for neurobiological studies. J Neurosci Res. 1988 Oct-Dec;21(2-4):521–530. [PubMed]
  • Kurihara T, Tsukada Y. The regional and subcellular distribution of 2',3'-cyclic nucleotide 3'-phosphohydrolase in the central nervous system. J Neurochem. 1967 Dec;14(12):1167–1174. [PubMed]
  • Koh JY, Choi DW. Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Methods. 1987 May;20(1):83–90. [PubMed]
  • Prohaska JR, Clark DA, Wells WW. Improved rapidity and precision in the determination of brain 2',3'-cyclic nucleotide 3'-phosphohydrolase. Anal Biochem. 1973 Nov;56(1):275–282. [PubMed]
  • McMorris FA, Smith TM, Sprinkle TJ, Auszmann JM. Induction of myelin components: cyclic AMP increases the synthesis rate of 2',3'-cyclic nucleotide 3'-phosphohydrolase in C6 glioma cells. J Neurochem. 1985 Apr;44(4):1242–1251. [PubMed]
  • McMorris FA. Cyclic AMP induction of the myelin enzyme 2',3'-cyclic nucleotide 3'-phosphohydrolase in rat oligodendrocytes. J Neurochem. 1983 Aug;41(2):506–515. [PubMed]
  • McMorris FA, Smith TM, DeSalvo S, Furlanetto RW. Insulin-like growth factor I/somatomedin C: a potent inducer of oligodendrocyte development. Proc Natl Acad Sci U S A. 1986 Feb;83(3):822–826. [PubMed]
  • Faden AI, Demediuk P, Panter SS, Vink R. The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science. 1989 May 19;244(4906):798–800. [PubMed]

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