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NKp46 and NKG2D receptor expression in NK cells with CD56 dim and CD56 bright phenotype: regulation by histamine and reactive oxygen species
Author(s) -
Romero Ana I.,
Thorén Fredrik B.,
Brune Mats,
Hellstrand Kristoffer
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05842.x
Subject(s) - nkg2d , natural killer cell , receptor , microbiology and biotechnology , biology , mhc class i , major histocompatibility complex , lymphokine activated killer cell , histamine , cytotoxicity , immunology , interleukin 12 , antigen , in vitro , cytotoxic t cell , biochemistry , pharmacology
Summary 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 H 2 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.