Serotonin protects NK cells against oxidatively induced functional inhibition and apoptosis.
High concentrations of the neurotransmitter serotonin can be found in inflamed and ischemic peripheral tissues, but the role of serotonin in immunoregulation is largely unknown. Here we report that serotonin protected human natural-killer (NK) cells from oxidatively induced inhibition inflicted by autologous monocytes in vitro. Serotonin protected NK cells from monocyte-mediated apoptosis and suppression of cytotoxicity and maintained the activation of NK cells induced by interleukin-2 despite the presence of inhibitory monocytes. A detailed analysis of these protective effects revealed that serotonin scavenged reactive oxygen species (ROS) derived from the H(2)O(2)-myeloperoxidase (-MPO) system. Serotonin shared this scavenger activity with its precursor, 5-hydroxytryptophan (5-HTP); however, serotonin was >10-fold more potent than 5-HTP in protecting NK cells against functional inhibition and apoptosis. We propose that serotonin, by scavenging peroxidase-derived ROS, may serve to protect NK cells from oxidative damage at inflammatory sites.
Betten
A
A
Department of Virology, Göteborg University, Sweden. Aasa.Betten@micribio.gu.se
Dahlgren
C
C
Hermodsson
S
S
Hellstrand
K
K
D006916:5-Hydroxytryptophan / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010084:Oxidation-Reduction; D009195:Peroxidase; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D016166:Free Radical Scavengers; D007376:Interleukin-2; D017382:Reactive Oxygen Species; D012701:Serotonin; D006861:Hydrogen Peroxide; D006916:5-Hydroxytryptophan; D009195:Peroxidase