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Viricidal effect of polymorphonuclear leukocytes on human immunodeficiency virus-1. Role of the myeloperoxidase

S J Klebanoff1, R W Coombs

  • 1Department of Medicine, University of Washington, Seattle 98195.

The Journal of Clinical Investigation
|June 1, 1992
PubMed

Insights

Neutrophilic polymorphonuclear leukocytes (PMN) use myeloperoxidase (MPO), hydrogen peroxide (H2O2), and chloride to fight HIV-1. This antimicrobial system, when activated, generates hypochlorous acid, which is toxic to the virus.

Area of Science:

  • Immunology
  • Microbiology
  • Biochemistry

Background:

  • Neutrophilic polymorphonuclear leukocytes (PMN) possess an antimicrobial system involving myeloperoxidase (MPO), hydrogen peroxide (H2O2), and chloride ions.
  • This system is known to be effective against various microorganisms.

Purpose of the Study:

  • To investigate the role of the MPO-H2O2-chloride system in the viricidal activity of PMN against HIV-1.
  • To elucidate the specific components and mechanisms involved in PMN-mediated HIV-1 inactivation.

Main Methods:

  • Normal human PMN and PMN from patients with chronic granulomatous disease (CGD) or MPO deficiency were stimulated.
  • Viricidal activity against HIV-1 was assessed under various conditions, including chloride replacement, addition of inhibitors (azide, catalase), and supplementation with H2O2 or MPO.
  • The involvement of MPO, H2O2, and chloride was inferred based on the modulation of viricidal activity.

Main Results:

  • Stimulated normal human PMN exhibited viricidal activity against HIV-1, dependent on chloride, MPO, and H2O2.
  • PMN from CGD patients lacked viricidal activity unless supplemented with H2O2, implicating endogenous MPO.
  • PMN from MPO-deficient patients showed reduced activity unless supplemented with MPO, implicating endogenous H2O2.

Conclusions:

  • The MPO-H2O2-chloride system in stimulated PMN generates a product, likely hypochlorous acid, that is toxic to HIV-1.
  • This viricidal mechanism may play a role in host defense against HIV-1 infection.

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