       Document 0104
 DOCN  M9550104
 TI    Regulation of nitric oxide synthase activity in human immunodeficiency
       virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated
       neurological disease.
 DT    9505
 AU    Bukrinsky MI; Nottet HS; Schmidtmayerova H; Dubrovsky L; Flanagan CR;
       Mullins ME; Lipton SA; Gendelman HE; Picower Institute for Medical
       Research, Manhasset, New York; 11030.
 SO    J Exp Med. 1995 Feb 1;181(2):735-45. Unique Identifier : AIDSLINE
       MED/95138705
 AB    Mononuclear phagocytes (monocytes, macrophages, and dendritic cells)
       play major roles in human immunodeficiency virus (HIV) persistence and
       disease pathogenesis. Macrophage antigen presentation and effector cell
       functions are impaired by HIV-1 infection. Abnormalities of macrophage
       effector cell function in bone marrow, lung, and brain likely result as
       a direct consequence of cellular activation and HIV replication. To
       further elucidate the extent of macrophage dysfunction in HIV-1 disease,
       a critical activation-specific regulatory molecule, nitric oxide (NO.),
       which may contribute to diverse pathology, was studied. Little, if any,
       NO. is produced by uninfected human monocytes. In contrast, infection
       with HIV-1 increases NO. production to modest, but significant levels
       (2-5 microM). Monocyte activation (with lipopolysaccharide, tumor
       necrosis factor alpha, or through interactions with astroglial cells)
       further enhances NO. production in HIV-infected cells, whereas its
       levels are diminished by interleukin 4. These results suggest a possible
       role for NO. in HIV-associated pathology where virus-infected
       macrophages are found. In support of this hypothesis, RNA encoding the
       inducible NO synthase (iNOS) was detected in postmortem brain tissue
       from one pediatric AIDS patient with advanced HIV encephalitis.
       Corresponding iNOS mRNA was not detected in brain tissue from five AIDS
       patients who died with less significant brain disease. These results
       demonstrate that HIV-1 can influence the expression of NOS in both
       cultured human monocytes and brain tissue. This newly described feature
       of HIV-macrophage interactions suggests previously unappreciated
       mechanisms of tissue pathology that result from productive viral
       replication.
 DE    Amino Acid Oxidoreductases/GENETICS/*METABOLISM  Astrocytes/VIROLOGY
       Base Sequence  Brain Diseases/*ENZYMOLOGY/VIROLOGY  Cells, Cultured  DNA
       Primers  Encephalitis/ENZYMOLOGY/VIROLOGY  Enzyme Induction  Human
       HIV-1/*PHYSIOLOGY  Molecular Sequence Data
       Monocytes/ENZYMOLOGY/*VIROLOGY  Nitric Oxide/BIOSYNTHESIS
       RNA/METABOLISM  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Tumor Cells, Cultured  JOURNAL ARTICLE

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

