Serotonin protects NK cells against oxidatively induced functional inhibition and apoptosis

High concentrations of the neurotransmitter serotonin can be found in infla med and ischemic peripheral tissues, but the role of serotonin in immunoreg ulation is largely unknown. Here we report that serotonin protected human n atural-killer (NK) cells from oxidatively induced inhibition inflicted by a utologous monocytes in vitro. Serotonin protected Nh cells from monocyte-me diated apoptosis and suppression of cytotoxicity and maintained the activat ion of NK cells induced by interleukin-2 despite the presence of inhibitory monocytes. A detailed analysis of these protective effects revealed that s erotonin scavenged reactive oxygen species (ROS) derived from the H2O2-myel operoxidase (-MPO) system, Serotonin shared this scavenger activity with it s 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 s ites.