title: HIV-1-infected monocytes and monocyte-derived macrophages are impaired in their ability to produce superoxide radicals.
abstract: Monocytes and monocyte-derived macrophages play a key role in immune defense against pathogenic organisms. Superoxide anion production is a key mechanism by which phagocytes kill pathogens. We sought to determine whether human immunodeficiency virus-infected monocytes and monocyte-derived macrophages are compromised in their ability to produce the superoxide anion following stimulation with phorbol myristate acetate (PMA) or after cross-linking the type I Fc receptor for IgG (Fc gamma RI). Fc gamma RI was cross-linked by the binding of monoclonal antibody 197, which reacts with an epitope of Fc gamma RI via its Fc region. Monocytes and monocyte-derived macrophages obtained from seronegative donors were infected in vitro with human immunodeficiency virus-1JR-FL and used in effector assays that measured superoxide anion production by the reduction of nitroblue tetrazolium. Reduced nitroblue tetrazolium was measured spectrophotometrically and by microscopy in which the percentage of cells containing intracellular deposits of the dye was assessed. By spectrophotometric measurement, we found that human immunodeficiency virus-infected monocytes and monocyte-derived macrophages produced less superoxide anion following either phorbol myristate acetate stimulation or Fc gamma RI cross-linking than uninfected cells from the same donor. Using microscopy we saw no difference in the percentage of infected and uninfected macrophages containing intracellular deposits of nitroblue tetrazolium suggesting that human immunodeficiency virus-infected macrophages produce less superoxide anion on a per cell basis than uninfected macrophages. Activation of human immunodeficiency virus-infected monocytes with interferon-gamma for 72 h prior to stimulation with phorbol myristate acetate or monoclonal antibody 197 increased their ability to reduce nitroblue tetrazolium. These findings suggest that impairment in the production of reactive oxygen intermediates may, in some cases, contribute to the pathogenesis of human immunodeficiency virus infection and the acquired immunodeficiency syndrome.
authors.affiliation: V. A. Medical Center, Research Service, White River Junction, VT 05009, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Howell
authors.forename: D S
authors.initials: DS
authors.lastname: Groveman
authors.forename: P K
authors.initials: PK
authors.lastname: Wallace
authors.forename: M W
authors.initials: MW
authors.lastname: Fanger
mesh_terms: D000838:Anions / Q000378:metabolism; D000914:Antibodies, Viral / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism / Q000821:virology*; D009580:Nitroblue Tetrazolium; D017452:Receptors, IgG / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000838:Anions; D000914:Antibodies, Viral; D002273:Carcinogens; D003432:Cross-Linking Reagents; D017452:Receptors, IgG; D013481:Superoxides; D009580:Nitroblue Tetrazolium; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate