Document 0712
 DOCN  M9440712
 TI    gp120 HIV envelope glycoprotein increases the production of nitric oxide
       in human monocyte-derived macrophages.
 DT    9404
 AU    Pietraforte D; Tritarelli E; Testa U; Minetti M; Department of Cell
       Biology, Istituto Superiore di Sanita, Rome,; Italy.
 SO    J Leukoc Biol. 1994 Feb;55(2):175-82. Unique Identifier : AIDSLINE
       MED/94132723
 AB    The effect of recombinant gp120 HIV envelope glycoprotein on the
       generation of free radicals by monocyte-derived macrophages (MDM) was
       measured by EPR spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide
       (DMPO). After 1 day in culture, MDM produced a spin trap adduct of DMPO
       with hyperfine splitting constants superimposable on those of DMPO-OH.
       The addition of gp120 to MDM increased the production of DMPO-OH and
       after 1 h, the amount of DMPO-OH produced by 40 micrograms/ml gp120 was
       about 300% that of untreated MDM. The use of selective inhibitors
       suggested the participation of the nitric oxide/L-arginine oxidative
       pathway, but did not provide evidence for trapping of hydroxyl radical
       or other oxygen free radicals. The specificity of gp120 was proven by
       two different anti-gp120 antibodies that either inhibited (polyclonal)
       or increased (monoclonal) the production of free radicals. Dexamethasone
       inhibited the effect of gp120, suggesting the possible involvement of an
       inducible nitric oxide (NO) synthase. Moreover, treatment of MDM with
       gp120 for 15 h increased in a dose-dependent manner the production of
       NO2-, a stable end product of NO. Soluble CD4 did not modify the
       intensity of the DMPO-OH adduct, whereas yeast mannan and
       Ca(2+)-chelators abolished the increase in the DMPO-OH signal induced by
       gp120. These data suggest the possible involvement of mannose-specific
       endocytotic lectin of MDM. The reaction of DMPO with sodium
       nitroprusside, an organic nitrate that releases NO, also produced
       DMPO-OH. Our findings indicate that gp120 increases free radical
       production from MDM as detected by spin-trapping methods, and that the
       spin trap adduct results from a reaction involving NO or closely related
       oxidized derivatives.
 DE    Adult  Arginine/ANALOGS & DERIVATIVES/PHARMACOLOGY
       Catalase/PHARMACOLOGY  Cells, Cultured  Coumarins  Cyclic N-Oxides
       Dexamethasone/PHARMACOLOGY  Dose-Response Relationship, Drug  Electron
       Spin Resonance Spectroscopy  Female  Free Radical Scavengers  Human  HIV
       Envelope Protein gp120/*PHARMACOLOGY  Kinetics
       Macrophages/CYTOLOGY/DRUG EFFECTS/*PHYSIOLOGY  Male
       Mannans/PHARMACOLOGY  Monocytes/CYTOLOGY/*PHYSIOLOGY  Nitric
       Oxide/*BIOSYNTHESIS  Recombinant Proteins/PHARMACOLOGY  Superoxide
       Dismutase/PHARMACOLOGY  Support, Non-U.S. Gov't  Time Factors  JOURNAL
       ARTICLE

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