Human immunodeficiency virus-1-infected macrophages induce inducible nitric oxide synthase and nitric oxide (NO) production in astrocytes: astrocytic NO as a possible mediator of neural damage in acquired immunodeficiency syndrome.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Blood. 1999 Mar 15;93(6):1843-50. Unique Identifier : AIDSLINE MED/99168971
Hori K; Burd PR; Furuke K; Kutza J; Weih KA; Clouse KA; Division of Cytokine Biology and the Division of Cellular and; Gene Therapies, Center for Biologics Evaluation and Research,; Food and Drug Administration, Rockville, MD, USA.

Abstract: Nitric oxide (NO) plays an important role in normal neural cell function. Dysregulated or overexpression of NO contributes to neurologic damage associated with various pathologies, including human immunodeficiency virus (HIV)-associated neurological disease. Previous studies suggest that HIV-infected monocyte-derived macrophages (MDM) produce low levels of NO in vitro and that inducible nitric oxide synthase (iNOS) is expressed in the brain of patients with neurologic disease. However, the levels of NO could not account for the degree of neural toxicity observed. In this study, we found that induction of iNOS with concomitant production of NO occurred in primary human astrocytes, but not in MDM, when astrocytes were cocultured with HIV-1-infected MDM. This coincided with decreased HIV replication in infected MDM. Supernatants from cocultures of infected MDM and astrocytes also stimulated iNOS/NO expression in astrocytes, but cytokines known to induce iNOS expression (interferon-gamma, interleukin-1beta, and tumor necrosis factor-alpha) were not detected. In addition, the recombinant HIV-1 envelope protein gp41, but not rgp120, induced iNOS in cocultures of uninfected MDM and astrocytes. This suggests that astrocytes may be an important source of NO production due to dysregulated iNOS expression and may constitute one arm of the host response resulting in suppression of HIV-1 replication in the brain. It also leads us to speculate that neurologic damage observed in HIV disease may ensue from prolonged, high level production of NO.

Keywords: JOURNAL ARTICLE Acquired Immunodeficiency Syndrome/*PATHOLOGY Astrocytes/DRUG EFFECTS/ENZYMOLOGY/*METABOLISM Cells, Cultured Coculture Embryo Enzyme Induction Human HIV Envelope Protein gp41/PHARMACOLOGY HIV-1/*PHYSIOLOGY Macrophages/ENZYMOLOGY/PHYSIOLOGY/*VIROLOGY Monocytes/VIROLOGY Neurons/PATHOLOGY Nitric Oxide/*BIOSYNTHESIS Nitric-Oxide Synthase/*BIOSYNTHESIS Recombinant Proteins/PHARMACOLOGY Virus Replication
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A9960998

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