Expression of inducible nitric oxide synthase in cytomegalovirus-infected glial cells of retinas from AIDS patients

Dighiero, P.; Reux, I.; Hauw, Jean‐Jacques; Fillet, Anne Marie; Courtois, Yves; Goureau, Olivier

doi:10.1016/0304-3940(94)90833-8

Cited by 64 publications

(30 citation statements)

References 12 publications

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“…In the human central nervous system, NOS2 has been detected in glial cells during cytomegalovirus infection (25), in extracted brain tissue from a patient with AIDSassociated cerebritis (26), in reactive astrocytes (27) and extracted brain tissue (28) from patients with multiple sclerosis, and in brain microvessels from patients with AD (29). To our knowledge, the evidence herein is the first to localize NOS2 to neurons in human brain.…”

Section: Discussionmentioning

confidence: 76%

Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.

Vodovotz

Lucia

Flanders

et al. 1996

The Journal of Experimental Medicine

264

169

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In Alzheimer's disease (AD), affected neurons accumulate beta amyloid protein, components of which can induce mouse microglia to express the high-output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice, NOS2 is normally suppressed by transforming growth factor beta 1 (TGF-beta 1). Expression of TGF-beta 1 is decreased in brains from AD patients, a situation that might be permissive for accumulation of NOS2. Accordingly, we investigated the expression of NOS2 in patients with AD, using three monospecific antibodies: a previously described polyclonal and two new monoclonal antibodies. Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was undetectable in brains from 6 control subjects aged 23-72 years, but was expressed in small amounts in 3 control subjects aged 77-87 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD.

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Section: Discussionmentioning

confidence: 76%

Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.

Vodovotz

Lucia

Flanders

et al. 1996

The Journal of Experimental Medicine

264

169

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“…Although NO might act as an antimicrobial and antiviral effector molecule in the retina (47), the sustained NO release by NOS-2 may cause retinal cell damage as we previously observed in the case of retinal light damage (48) or during endotoxin-induced uveitis (27). Type I IFNs are produced by various cell types in the early phase of viral or bacterial infection.…”

Section: Fig 4 Effect Of Ifn-␣ and Ifn-␤ On Nos-2 Mrna Stability Inmentioning

confidence: 82%

Inhibition of Inducible Nitric Oxide Synthase Expression by Interferons α and β in Bovine Retinal Pigmented Epithelial Cells

Faure

Courtois

Goureau

1997

Journal of Biological Chemistry

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“…Other investigators have reported that infection with various viruses induces expression of iNOS in vitro (12,13,15,(28)(29)(30)(31). MacMicking and associates (13) have observed that transfection of iNOS cDNA into cells in culture decreases viral titer in these cells.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide inhibits viral replication in murine myocarditis.

Lowenstein¹,

Hill²,

et al. 1996

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Nitric oxide (NO) is a radical molecule that not only serves as a vasodilator and neurotransmitter but also acts as a cytotoxic effector molecule of the immune system. The inducible enzyme making NO, inducible NO synthase (iNOS), is transcriptionally activated by IFN-␥ and TNF-␣ , cytokines which are produced during viral infection. We show that iNOS is induced in mice infected with the Coxsackie B3 virus. Macrophages expressing iNOS are identified in the hearts and spleens of infected animals with an antibody raised against iNOS. Infected mice have increased titers of virus and a higher mortality when fed NOS inhibitors. Thus, viral infection induces iNOS in vivo, and NO inhibits viral replication. NO is a novel, nonspecific immune defense against viruses in vivo. (

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Expression of inducible nitric oxide synthase in cytomegalovirus-infected glial cells of retinas from AIDS patients

Cited by 64 publications

References 12 publications

Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.

Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.

Inhibition of Inducible Nitric Oxide Synthase Expression by Interferons α and β in Bovine Retinal Pigmented Epithelial Cells

Nitric oxide inhibits viral replication in murine myocarditis.

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