Monocyte-mediated suppression of IL-2-induced NK-cell activation. Regulation by 5-HT1A-type serotonin receptors.
In the present study, the effects of serotonin on human natural killer (NK)-cell responsiveness to interleukin 2 (IL-2) was investigated. Concomitant treatment of human lymphocytes, enriched for NK effector cells by Percoll density-gradient centrifugation, with serotonin and IL-2 yielded a synergistic activation of NK-cell cytotoxicity (NKCC) in the presence but not in the absence of monocytes. The monocyte-dependent, regulatory effects of serotonin and/or IL-2 were prostaglandin-independent and could be reconstituted when monocytes, recovered by countercurrent centrifugal elutriation (CCE), were added to purified NK effector cells. The effects of serotonin on baseline and IL-2-activated NK cells were mimicked by the 5-HT1A receptor-specific agonists 8-OH-DPAT and (+)-ALK. Our data suggest that serotonin regulates NK-cell responsiveness to IL-2 via 5-HT1A receptors.
Hellstrand
K
K
Department of Clinical Virology, University of Göteborg, Sweden.
Hermodsson
S
S
D002469:Cell Separation; D016861:Cyclooxygenase Inhibitors; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004357:Drug Synergism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010641:Phenotype; D011985:Receptors, Serotonin / Q000502:physiology*; D011994:Recombinant Proteins; D012701:Serotonin / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D007376:Interleukin-2; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D007213:Indomethacin