Serotonin Receptor Regulation of Eosinophil Transendothelial Migration

Abstract

Abstract Previous research has shown that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic inflammation in the lung by inhibiting eosinophil migration across endothelial monolayers. Furthermore, when the metabolic conversion of 5HTP to serotonin is blocked, 5HTP inhibition of eosinophil migration is reduced. Therefore, 5HTP metabolism to serotonin is required for 5HTP inhibition of eosinophil migration. However, it is currently unknown if serotonin receptors are involved in mediating 5HTP function. We determined serotonin receptor expression on both endothelial cells and eosinophils by western blot and qPCR. Endothelial cells and eosinophils expressed serotonin receptors 1A, 1B, 3A, and 6. We subsequently determined whether inhibition of these serotonin receptors abrogates the effects of 5HTP. Notably, it was shown that blocking serotonin binding to serotonin receptors 1A and 1B by use of selective receptor inhibitors blocks 5HTP inhibition of migration. The function of signaling by serotonin receptors in 5HTP-mediated inhibition of migration is under investigation. Thus, serotonin receptors mediate 5HTP inhibition of transendothelial migration, and may serve as a target for intervention during allergic inflammation. These results will help design ongoing clinical studies addressing whether 5HTP blocks allergic asthmatic responses.