Serotonin acts as a radical scavenger and is oxidized to a dimer during the respiratory burst of human mononuclear and polymorphonuclear phagocytes*

Abstract

Isolated human mononuclear and polymorphonuclear phagocytes were stimulated in the presence and absence of serotonin (5-HT), the major secretory product of activated platelets, and the release of reactive oxygen metabolites during the respiratory burst was assessed by luminol-enhanced chemiluminescence. In the presence of 5-HT, a dose-dependent suppression of the chemiluminescence signal occurred, irrespective of the stimulus used to elicit the respiratory burst. A similar suppression of luminol-enhanced chemiluminescence was also seen in a radical generating cell free system. 5-HT was found to be oxidized by the reactive oxygen species released by stimulated phagocytes. This oxidation is prevented in the presence of other antioxidants. The major 5-HT oxidation product was isolated by gel chromatography and identified by mass-spectrometry as a 5-HT dimer, probably 5,5'-dihydroxy-4,4'-bitryptamine. It is concluded that the 5-HT released from activated thrombocytes at sites of inflammation and endothelial cell damage acts as a true scavenger of reactive oxygen species generated during the respiratory burst of stimulated phagocytes and may thus modulate various aspects of cell-mediated defence reactions.