Serotonin and its 5-HT2 receptor agonist DOI hydrochloride inhibit the oxidative burst in total leukocytes but not in isolated neutrophils

AimsSerotonin (5-HT) is capable of reducing the oxidative burst of professional phagocytes. In this study, we investigated whether 5-HT mediates this modulation via 5-HT receptors (5-HTR) or whether this is due instead to 5-HT antioxidative properties.Main methodsThe leukocytes or polymorphonuclear leukocytes (PMNL) were isolated from human blood, and their ability to produce reactive oxygen species (ROS) after 5-HT or its agonist treatment was tested by luminol-enhanced chemiluminescence (CL) analysis.Key findingsIt was found that 5-HTR2 agonist DOI hydrochloride does not have any antioxidative properties, despite its ability to inhibit the CL response of activated human total leukocytes. On the other hand, DOI hydrochloride was unable to inhibit the CL response of activated human PMNL. It seems that the reduction of the oxidative burst of professional phagocytes was evoked by the activation of 5-HTR not on the neutrophil surface but on the surface of different leukocytes, which produced anti-inflammatory cytokines with NADPH oxidase activity modulating properties.SignificancePlatelets and activated PMNL are in tight contact at sites of inflammation. 5-HT released from platelets might have a protective function against PMNL-derived oxidative stress and oxidative damages.