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Oxygen radical-induced natural killer cell dysfunction: role of myeloperoxidase and regulation by serotonin

Journal article
Authors Åsa Betten
Claes Dahlgren
Ulf-Henrik Mellqvist
Svante Hermodsson
Kristoffer Hellstrand
Published in J Leukoc Biol
Volume 75
Issue 6
Pages 1111-5
Publication year 2004
Published at Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research
Institute of Internal Medicine, Dept of Medicine
Institute of Laboratory Medicine, Dept of Clinical Virology
Pages 1111-5
Language en
Keywords Ceruloplasmin/pharmacology, Cytotoxicity, Immunologic, Free Radical Scavengers/*pharmacology, Humans, Hydrogen Peroxide/metabolism, K562 Cells, Killer Cells, Natural/*drug effects/enzymology, Lymphocytes/enzymology, Monocytes/cytology/immunology, NADPH Oxidase/metabolism, Peroxidase/antagonists & inhibitors/*physiology, Phagocytes, Reactive Oxygen Species/*metabolism, Research Support, Non-U.S. Gov't, Serotonin/*pharmacology
Subject categories Medical and Health Sciences


Natural killer (NK) cells are functionally suppressed and induced to apoptosis by reactive oxygen species (ROS) produced by mononuclear phagocytes (MPs). These inhibitory events are reversed by the biogenic amine serotonin. MPs generate hydrogen peroxide (H(2)O(2)), which is processed further by myeloperoxidase (MPO) to even more toxic compounds. Earlier studies suggest that serotonin scavenges MP-derived oxygen radicals generated by the MPO-H(2)O(2) system. These findings led us to explore the capability of MPO-deficient MPs to induce NK cell dysfunction. We show that MPs recovered from subjects with MPO deficiency trigger inhibition of NK cells. In addition, MPs recovered from healthy subjects conveyed suppression of NK cells in the presence of the MPO inhibitor ceruloplasmin. We conclude that ROS-dependent inhibition of NK cell function is unrestricted by the availability of MPO-derived oxygen radicals and that the protecting properties of serotonin may operate in the absence of functional MPO. Our data suggest a complex mechanism of MP-induced NK cell inhibition, which comprises the generation of interchangeable oxygen radicals.

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