Role of platelet serotonin in innate immune cell recruitment

Serotonin (5-Hydroxytryptamine, 5-HT) was discovered as a vasoconstrictor in 1937. Since its discovery, the involvement of serotonin in numerous physiological processes was described. It acts as an important neurotransmitter, regulates bowel movement, can be released as a tissue hormone and acts as a growth factor. Among the years, a link between serotonin and inflammation has been identified and further evidence suggests an important role of serotonergic components in immune responses. Peripheral serotonin is synthesized by the enzyme tryptophan hydroxylase (Tph), which exists in two different isoforms: Tph2 being responsible for serotonin synthesis in neurons and Tph1 for generation of serotonin in peripheral organs. After synthesis in intestinal enterochromaffin cells, serotonin is stored in platelets and released upon stimulation. Several immune cells express the serotonin transporter SERT and enzymes for serotonin metabolism (monoamine oxygenase, MAO). To be susceptible to changes in serotonin levels, serotonin receptors are required and almost all of the 15 receptor subtypes are represented on immune cells. In this review, we describe the distribution of serotonergic components in cells of the immune system and the impact of platelet-derived serotonin on these cells. In particular, we aim to understand the effect of serotonin on immune cell recruitment to sites of inflammation.