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HIV-1-infected monocytes and monocyte-derived macrophages are impaired in their ability to produce Superoxide radicals

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International Journal of Clinical and Laboratory Research

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 (FcγRI). FcγRI was cross-linked by the binding of monoclonal antibody 197, which reacts with an epitope of FcγRI located outside the ligand binding site and also binds FcγRI 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 FcγRI 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-γ 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.

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Authors and Affiliations

  1. V. A. Medical Center, Research Service, 215 N. Main Street, Box 151C, 05009, White River Junction, VT, USA

    A. L. Howell

  2. Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire, USA

    A. L. Howell, D. S. Groveman, P. K. Wallace & M. W. Fanger

  3. Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA

    A. L. Howell & M. W. Fanger

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  1. A. L. Howell
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  2. D. S. Groveman
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  3. P. K. Wallace
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  4. M. W. Fanger
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Howell, A.L., Groveman, D.S., Wallace, P.K. et al. HIV-1-infected monocytes and monocyte-derived macrophages are impaired in their ability to produce Superoxide radicals. Int J Clin Lab Res 27, 111–117 (1997). https://doi.org/10.1007/BF02912444

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