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Titolo:
Cytokine-stimulated, but not HIV-infected, human monocyte-derived macrophages produce neurotoxic levels of L-cysteine
Autore:
Yeh, MW; Kaul, M; Zheng, JL; Nottet, HSLM; Thylin, M; Gendelman, HE; Lipton, SA;
Indirizzi:
Burnham Inst, Ctr Neurosci & Aging, La Jolla, CA 92037 USA Burnham Inst La Jolla CA USA 92037 urosci & Aging, La Jolla, CA 92037 USA Harvard Univ, Sch Med, Brigham & Womens Hosp, Cerebrovasc & Neurosci Res Inst, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 Neurosci Res Inst, Boston, MA 02115 USA Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA Univ Nebraska Omaha NE USA 68198 Pathol & Microbiol, Omaha, NE 68198 USA Univ Nebraska, Med Ctr, Dept Med, Ctr Neurovirol & Neurogenerat Disorders,Omaha, NE 68198 USA Univ Nebraska Omaha NE USA 68198 urogenerat Disorders,Omaha, NE 68198 USA Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198USA Univ Nebraska Omaha NE USA 68198 es Canc & Allied Dis, Omaha, NE 68198USA Eijkman Winkler Inst, Sect Neuroimmunol, Utrecht, Netherlands Eijkman Winkler Inst Utrecht Netherlands oimmunol, Utrecht, Netherlands
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 8, volume: 164, anno: 2000,
pagine: 4265 - 4270
SICI:
0022-1767(20000415)164:8<4265:CBNHHM>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CORTICAL CELL-CULTURES; COAT PROTEIN GP120; NF-KAPPA-B; MONONUCLEAR PHAGOCYTES; NERVOUS-SYSTEM; NITRIC-OXIDE; ENVELOPE GLYCOPROTEIN; SPHINGOMYELIN PATHWAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Lipton, SA Burnham Inst, Ctr Neurosci & Aging, 10901 N Torrey Pines Rd, LaJolla, CA 92037 USA Burnham Inst 10901 N Torrey Pines Rd La Jolla CA USA 92037 USA
Citazione:
M.W. Yeh et al., "Cytokine-stimulated, but not HIV-infected, human monocyte-derived macrophages produce neurotoxic levels of L-cysteine", J IMMUNOL, 164(8), 2000, pp. 4265-4270

Abstract

Approximately one-quarter of individuals with AIDS develop neuropathological symptoms that are attributable to infection of the brain with HIV, The cognitive manifestations have been termed HIV-associated dementia, The mechanisms underlying HIV-associated neuronal injury are incompletely understood, but various studies have, confirmed the release of neurotoxins by macrophages/microglia infected with HIV-1 or stimulated by viral proteins, including the envelope glycoprotein gp120, In the present study, we investigated the possibility that L-cysteine, a neurotoxin acting at the N-methyl-D-aspartate subtype of glutamate receptor, could contribute to HN-associated neuronal injury. Picomolar concentrations of gp120 were found to stimulate cysteine release from human monocyte-derived macrophages (hMDM) in amounts sufficient to injure cultured rat cerebrocortical neurons, TNF-alpha and IL-1 beta, known to be increased in HIV-encephalitic brains, as well as a cellularproduct of cytokine stimulation, ceramide, were also shown to induce release of cysteine from hMDM in a dose-dependent manner. A TNF-alpha-neutralizing Ab and an IL-1 beta R antagonist partially blocked gp120-induced cysteine release, suggesting that these cytokines may mediate the actions of gp120. Interestingly, hMDM infected with HIV-1 produced significantly less cysteine than uninfected cells following stimulation with TNF-alpha. Our findings imply that cysteine may play a role in the pathogenesis of neuronal injury in HIV-associated dementia due to its release from immune-activated macrophages but not virus-infected macrophages, Such uninfected cells comprise the vast majority of mononuclear phagocytes (macrophages and microglia) found in HIV-encephalitic brains. The Journal of Immunology, 2000, 164: 4265-4270.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 12:21:42