Viricidal effect of polymorphonuclear leukocytes on human immunodeficiency virus-1. Role of the myeloperoxidase system.
Myeloperoxidase (MPO), H2O2, and chloride form an antimicrobial system in neutrophilic polymorphonuclear leukocytes (PMN) effective against a variety of microorganisms. Normal human PMN, when stimulated with phorbol myristate acetate or opsonized zymosan, are viricidal to HIV-1. The viricidal effect was lost when chloride was replaced by sulfate and was inhibited by the peroxidase inhibitor azide and by catalase, but not by heated catalase or superoxide dismutase, implicating H2O2. Stimulated PMN from patients with chronic granulomatous disease (CGD) were not viricidal to HIV unless H2O2 or glucose oxidase (which generates H2O2) was added, and the viricidal activity of H2O2-supplemented CGD PMN was inhibited by azide, implicating endogenous MPO. Stimulated PMN from patients with hereditary MPO deficiency had decreased viricidal activity unless MPO was added, and the viricidal activity of MPO-supplemented, MPO-deficient PMN was inhibited by catalase, implicating endogenous H2O2. The data suggest that when PMN are stimulated, MPO released by degranulation reacts with H2O2 formed by the respiratory burst to oxidize chloride to a product (presumably hypochlorous acid) that is toxic to HIV-1. Our findings raise the possibility that this viricidal effect of stimulated PMN may influence the host defense against HIV-1.
Klebanoff
S J
SJ
Department of Medicine, University of Washington, Seattle 98195.
Coombs
R W
RW
D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism*
D002712:Chlorides; D006861:Hydrogen Peroxide; D009195:Peroxidase