Document 2545
 DOCN  M94A2545
 TI    HIV-1 infection alters response of macrophages to activating stimuli:
       implications for AIDS neuropathogenesis.
 DT    9412
 AU    Bukrinsky M; Nottet HS; Dubrovsky L; Schmidtmayerova H; Sherry B;
       Gendelman HE; Picower Institute for Medical Research, Manhasset, New
       York; 11030.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):28 (abstract no. 086A). Unique
       Identifier : AIDSLINE ICA10/94370030
 AB    Cells of the macrophage lineage play an important role in AIDS
       neuropathogenesis. Previously published reports demonstrated that
       neurotoxicity could be induced by NMDA receptor stimulation and was
       mediated, in part, by nitric oxide (NO). These results led us to
       investigate whether HIV-1 infection of human monocyte could induce NO.
       Productive HIV-1 replication in monocytes was associated with minimally
       elevated levels of nitrites. A marked increase in nitrite and nitric
       oxide synthase (NOS) mRNA was observed during coculture of
       virus-infected monocytes with astroglia. This corresponded to high
       levels of tumor necrosis factor (TNF) in the culture supernatant.
       Indeed, addition of TNF to HIV-infected monocytes reproduced induction
       of NOS activity seen during monocyte-astroglial cell coculture. The
       biological significance of this induction was revealed by the detection
       of NOS mRNA in brain tissue of some AIDS patients with encephalopathy.
       It appears that infection with HIV modifies the responses of monocytes
       to the signals from other cells (including astroglial cells). In
       particular, HIV-infected monocytes respond to TNF-alpha stimulation by
       activation of expression of NOS, which is not expressed by stimulated
       uninfected monocytes. These results, taken together, strongly suggest a
       NOS-mediated toxicity operative in the pathogenesis of HIV-related
       cognitive and motor dysfunction.
 DE    Acquired Immunodeficiency Syndrome/*IMMUNOLOGY  Amino Acid
       Oxidoreductases/METABOLISM  Astrocytes/METABOLISM  AIDS Dementia
       Complex/*MICROBIOLOGY  Brain/METABOLISM  Calmodulin-Binding
       Proteins/METABOLISM  Cells, Cultured  Human  HIV-1/*GROWTH & DEVELOPMENT
       *Macrophage Activation  Monocytes/METABOLISM/*MICROBIOLOGY  Nitrous
       Oxide/METABOLISM  NADPH Dehydrogenase/METABOLISM  Tumor Necrosis
       Factor/BIOSYNTHESIS  Virus Replication  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).