Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Monocyte-mediated suppression of IL-2-induced NK-cell activation. Regulation by 5-HT1A-type serotonin receptors. 211 76

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.
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PMID:Enhancement of human natural killer cell cytotoxicity by serotonin: role of non-T/CD16+ NK cells, accessory monocytes, and 5-HT1A receptors. 213 18

Autologous monocytes irreversibly suppressed functions of human natural killer (NK) cells including baseline and lymphokine-induced cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), and interleukin-2 (IL-2)-induced proliferation. The suppression of these NK-cell functions was cell contact-dependent and could be evoked only by purified monocytes, recovered directly from peripheral blood by countercurrent centrifugal elutriation (CCE). The presence of monocytes also induced the disappearance of CD16 and CD56 antigen on CD3- NK cells (CD3-/16+/56+-->CD3-/16-/56-). By contrast, T-cell proliferation and the expression of CD3 on CD56- T cells were not susceptible to cell contact-mediated suppression by monocytes. The biogenic amine serotonin abrogated monocyte-induced suppression of NK-cell functions as well as down-modulation of CD16/56 NK-cell antigen. Serotonin thus markedly augmented baseline and lymphokine-induced NK-cell cytotoxicity, ADCC, and NK-cell proliferation, and maintained the expression of NK-cell surface antigens in the presence of elutriated monocytes. The effect of serotonin was mediated by 5-HT1A-type serotonin receptors (5-HT1AR) as indicated by mimicry exerted by 5-HT1AR agonists such as 8-OH-DPAT and (+)-ALK, partial antagonism by the 5-HT1AR antagonists pindolol and cyproheptadine, and lack of antagonism by the 5-HT2R antagonist ketanserin or the 5-HT3R antagonist ondansetron. Our data are suggestive of a cell-to-cell-mediated mechanism by which monocytes down-modulate NK-cell function and phenotype and its serotonergic regulation.
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PMID:Serotonergic 5-HT1A receptors regulate a cell contact-mediated interaction between natural killer cells and monocytes. 767 81