A cell-to-cell mediated interaction involving monocytes and non-T/CD16+ natural killer (NK) cells is required for histamine H2-receptor-mediated NK-cell activation.
Histamine (10(-4) to 10(-7) M) augmented natural killer cell cytotoxicity (NKCC) of human CD16+, non-T lymphocytes in vitro against the NK-sensitive target cells K562 erythroleukaemic, Molt-4 lymphoma, Chang liver cells and against Epstein-Barr virus (EBV)-transformed, NK-insensitive Daudi B-lymphoblastoid target cells by a mechanism of action involving a prostaglandin- and interleukin 1 (IL-1)-independent accessory function of monocytes. No evidence for the production of intermediary, NK-enhancing cytokines by histamine was obtained, indicating a cell-to-cell mediated interaction between monocytes and NK cells as a plausible mechanism of action for the NK-augmenting effect. Monocytes recovered by countercurrent centrifugal elutriation (CCE), but not monocytes recovered by adherence, reconstituted the effect of histamine when added to non-adherent NK cells. The development of NKCC in response to histamine was time-dependent with (i) an induction phase, dependent on the presence of accessory monocytes and ongoing histamine H2-receptor activation (half-maximal response required approximately 30 min treatment of large granular lymphocyte (LGL)-enriched lymphocytes and monocytes with histamine), and (ii) an effector phase, independent of the presence of monocytes or histamine receptor activation. Histamine-activated mononuclear cells (MNC) continued to exert augmented cytotoxicity for at least 8 h after removal of histamine and monocytes. In several experiments, histamine-activated NK-effector cells killed greater than 90% of the target cells at low baseline NKCC. We suggest that histamine may have a role in non-specific tumour defence by regulating an earlier unrecognized interplay between monocytes and NK cells.
Hellstrand
K
K
Department of Clinical Virology, University of Göteborg, Sweden.
Hermodsson
S
S
D000943:Antigens, Differentiation / Q000276:immunology*; D002450:Cell Communication; D002460:Cell Line; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000096:biosynthesis; D007375:Interleukin-1 / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014176:Protein Biosynthesis; D011961:Receptors, Fc / Q000276:immunology*; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000943:Antigens, Differentiation; D007375:Interleukin-1; D007376:Interleukin-2; D011961:Receptors, Fc; D011970:Receptors, Histamine H2; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine; D007372:Interferons; D011451:Prostaglandin-Endoperoxide Synthases