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).