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M9550104.TXT
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1995-03-04
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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).