       Document 0521
 DOCN  M9630521
 TI    Human immunodeficiency virus type 1 envelope protein does not stimulate
       either prostaglandin formation or the expression of prostaglandin H
       synthase in THP-1 human monocytes/macrophages.
 DT    9603
 AU    Hui R; Curtis JF; Sumner MT; Shears SB; Glasgow WC; Eling TE; Eicosanoid
       Biochemistry Section, National Institute of; Environmental Health
       Sciences, Research Triangle Park, North; Carolina 27709, USA.
 SO    J Virol. 1995 Dec;69(12):8020-6. Unique Identifier : AIDSLINE
       MED/96079052
 AB    Prostaglandin E2 is observed at elevated levels during human
       immunodeficiency virus (HIV) infection and thus may contribute to the
       HIV-dependent immunosuppression. The mechanisms responsible for this
       increase are not understood. Evidence indicates that the viral envelope
       proteins perturb membrane signaling mediated by the CD4 receptor,
       suggesting that the free envelope protein and/or the intact virus may be
       responsible for the increase in prostaglandin E2 levels. In this study,
       we have used THP-1 human monocytes and THP-1 cells differentiated by
       12-O-tetradecanoylphorbol-13-acetate treatment into macrophages to
       determine if the HIV envelope protein, gp120, or an anti-CD4 receptor
       antibody stimulates prostaglandin formation by interacting with the CD4
       receptor. Incubation of THP-1 cells with OKT4A antibody greatly
       stimulated the CD4-p56lck receptor complex as estimated by enhanced
       p56lck autophosphorylation, while the gp120 gave small but significant
       responses. Monocytic THP-1 cells poorly metabolized arachidonic acid to
       prostaglandin E2 and thromboxane B2 as measured by high-pressure liquid
       chromatography analysis. Western blot (immunoblot) and Northern (RNA)
       blot analyses revealed that unstimulated monocytes expressed little
       prostaglandin H synthase 1 and 2 (PGHS-1 and -2). Incubation of the
       monocytes with lipopolysaccharide, OKT4A, or gp120 did not increase the
       formation of prostaglandins. The expression of PGHS-1 or PGHS-2 was also
       not increased. Differentiation of the monocytes to macrophages by
       12-O-tetradecanoylphorbol-13-acetate treatment resulted in increased
       expression of PGHS-1 and increased formation of prostaglandins compared
       with that for the monocytes. Lipopolysaccharide stimulation of the
       macrophages increased the formation of prostaglandins and increased the
       expression of PGHS-2 in the macrophages. However, OKT4A or gp120
       preparation, at concentrations that stimulated p56lck
       autophosphorylation, did not enhance the formation of prostaglandins or
       the expression of PGHS-1 or PGHS-2. OKT4A and gp120 also did not
       stimulate the release of arachidonic acid, indicating that phospholipase
       A2 was not activated by the CD4 receptor in either the THP-1 monocytes
       or macrophages. These results indicate that activation of the CD4-p56lck
       receptor signal transduction pathway by the HIV envelope protein does
       not increase prostaglandin formation.
 DE    src-Family Kinases/METABOLISM  Animal  Antibodies,
       Monoclonal/PHARMACOLOGY  Antigens, CD4/PHYSIOLOGY  Cell Differentiation
       Cell Line  CHO Cells  Dinoprostone/ISOLATION & PURIF/METABOLISM
       Eicosanoids/METABOLISM  Enzyme Activation  Gene Expression  Hamsters
       Human  HIV Envelope Protein gp120/BIOSYNTHESIS/ISOLATION & PURIF/
       *PHARMACOLOGY  *HIV-1/*PHYSIOLOGY  Isoenzymes/BIOSYNTHESIS  Kinetics
       Macrophages/CYTOLOGY/*METABOLISM  Monocytes/CYTOLOGY/*METABOLISM
       Prostaglandin-Endoperoxide Synthase/*BIOSYNTHESIS
       Prostaglandins/*METABOLISM  Tetradecanoylphorbol Acetate/PHARMACOLOGY
       Thromboxane B2/ISOLATION & PURIF/METABOLISM  JOURNAL ARTICLE

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

