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NKp46 and NKG2D receptor expression in NK cells with CD56dim and CD56bright phenotype: regulation by histamine and reactive oxygen species

Journal article
Authors Ana Romero
Fredrik Bergh Thorén
Mats Brune
Kristoffer Hellstrand
Published in Br J Haematol
Volume 132
Issue 1
Pages 91-8
ISSN 0007-1048 (Print)
Publication year 2006
Published at Institute of Medicine, Department of Internal Medicine
Institute of Biomedicine, Department of Infectious Medicine
Pages 91-8
Language en
Keywords Antigens, CD56/ analysis, Apoptosis/immunology, Cells, Cultured, Down-Regulation/immunology, Flow Cytometry, Histamine/pharmacology, Humans, Immunophenotyping, Killer Cells, Natural/drug effects/immunology/ metabolism, Membrane Glycoproteins/drug effects/ metabolism, Neutrophil Activation/immunology, Neutrophils/immunology, Phagocytes/immunology, Reactive Oxygen Species/pharmacology, Receptors, Immunologic/drug effects/ metabolism, Up-Regulation/immunology
Subject categories Medical and Health Sciences


The cytotoxicity of natural killer (NK) cells is dependent on the interaction between target cell ligands and a series of stimulatory receptors on NK cells. Two of these triggering receptors, the NKp46 natural cytotoxicity receptor (NKp46) and the major histocompatibility complex (MHC) class I-interactive NKG2D receptor, are deficiently expressed by NK cells recovered from patients with acute myeloid leukaemia (AML), but little is known regarding the regulation of NKp46 and NKG2D expression. Here we report that mononuclear and polymorphonuclear phagocytes downregulate the cell surface density of NKp46 and NKG2D on NK cells with CD56(dim) phenotype in vitro by a mechanism that is dependent on the availability of phagocyte-derived reactive oxygen species (ROS). Histamine maintained NKp46 and NKG2D expression despite the presence of inhibitory phagocytes by targeting an H2 receptor on phagocytes. By contrast, NKp46 and NKG2D expression by the CD56(bright) subset of NK cells was resistant to inhibition by phagocytes. Our findings are suggestive of a novel mechanism of relevance to the regulation of NKp46/NKG2D receptor expression. Moreover, our findings suggest that the previously reported action of histamine on NK cell-mediated killing of leukaemic cells may be related to the preservation of activatory NK-cell receptors.

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