Enhancement of human natural killer cell cytotoxicity by serotonin: role of non-T/CD16+ NK cells, accessory monocytes, and 5-HT1A receptors.
Serotonin (10(-4) - 10(-7) M) augmented natural killer cell cytotoxicity (NKCC) of human CD16+/non-T lymphocytes in vitro against the NK-sensitive target cells K 562 erythroleukemic, Molt-4 lymphoma, Chang liver cells, and against EBV-transformed Daudi B-lymphoblastoid target cells by a mechanism of action involving a prostaglandin-and IL-1-independent accessory function of monocytes. No evidence for the production of intermediary, NK-enhancing cytokines by serotonin was obtained, suggesting 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 counter-current centrifugal elutriation but not monocytes recovered by adherence reconstituted the effect of serotonin when added to nonadherent NK cells. NK-enhancing effects of serotonin were mimicked by two 5-HT1A-type serotonin receptor agonists, 8-OH-DPAT and (+)-ALK. The development of NKCC in response to serotonin could be resolved into (i) an induction phase, dependent on the presence of accessory monocytes and serotonin, and (ii) an effector phase, independent of the presence of monocytes or serotonin. Serotonin-activated MNC continued to exert augmented cytotoxicity for at least 8 hr after the removal of serotonin and monocytes. In several experiments, serotonin-activated NK cells killed greater than 75% of K 562 target cells even at low effector to target cell ratios and low baseline NKCC. We suggest that serotonin may have a role in nonspecific tumor 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*; D001685:Biological Factors / Q000378:metabolism / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology; D016207:Cytokines; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology / Q000648:ultrastructure; D008223:Lymphoma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D009000:Monocytes / Q000276:immunology / Q000502:physiology / Q000648:ultrastructure; D010641:Phenotype; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D011985:Receptors, Serotonin / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
D000943:Antigens, Differentiation; D001685:Biological Factors; D016207:Cytokines; D011961:Receptors, Fc; D017452:Receptors, IgG; D011985:Receptors, Serotonin; D012701:Serotonin