Serotonin and adrenaline as inhibitors of neutrophil extracellular traps formation (experimental study)

Abstract

Regulation of the NETosis can provoke cancer, inflammatory and autoimmune diseases and become a basis for effective targeted therapy. The aim: to study the modifying effects of serotonin and adrenaline on NETosis during phagocytosis in rats.Materials and methods.Wistar rats were divided into control (solvent, 0.9% NaCl solution) and experimental (serotonin and adrenaline 1.43 and 0.143 mg/kg body weight, respectively) groups. Intraperitoneal injection of test substances was carried out 90 minutes before blood sampling, in which phagocytic activity (PhA), phagocytic index (PhI) and degree of suicidal neutrophil NETosis were determined: with total and partial chromatin decondensation (TCD, PCD, accordingly). A paired Student’s t test was used to compare groups with numerical values and McNemar’s test (for dichotomous variables). Pearson’s linear correlation coefficient (rxy) was assessed to measure a linear relationship between time points.Results.The administration of adrenaline contributed to NETosis inhibition by 41.5% compared to control group (p 0.001), serotonin — by 27.6% (p 0.001). The ratio of neutrophils with total and partial chromatin decondensation for control group was 1.0:0.9; for serotonin and adrenaline it changed to 1.0:1.7 and 1.0:1.4, respectively. Relative to control group, phagocytic index after serotonin administration increased by 4.9%, in case of adrenaline, on the contrary, it decreased by 12.4% (p 0.01). A high positive correlation was revealed between NETosis and phagocytic index for control group and experimental group with adrenaline: rxy= 0.823–0.997. For phagocytic index and NETosis in these groups there was a high negative (rxy= –0.714–(–0.871)) and a noticeable positive correlation for serotonin (rxy= 0.638).Conclusion.Serotonin and adrenaline in therapeutic dosages have a pronounced inhibitory effect on NETosis, which may pave the avenue for increasing the effectiveness of therapy for immunoinflammatory and oncological diseases. The use of serotonin is preferable because it has additional immunomodulatory effects and cause no direct stimulation ofα- andβ-adrenergic receptors.