Serotonin modulates the oxidative burst of human phagocytes via various mechanisms.
Serotonin, the major secretory product of activated platelets, has been widely reported as regulating various constituents of the immune system and immune functions. This modulation is complex and the data available are rather controversial. The aim of the present study was to clarify the mechanisms of serotonin action on human phagocytes. The effect of serotonin in a concentration range of 10(-7) M-10(-3) M on various parameters of oxidative burst of phagocytes was studied using various luminol-enhanced chemiluminescence methods. Serotonin inhibited the chemiluminescence response of the cells in a dose dependent manner. The effect of serotonin on the activity of myeloperoxidase was studied in further experiments. In this case, serotonin again exerted a dose dependent inhibition of the myeloperoxidase activity. The hypothesis that the inhibitory activity of serotonin might be also receptor mediated was evaluated using various serotonin receptor agonists and antagonists. None of the agonists studied exerted any direct antioxidative properties. Only (+/-)-DOI hydrochloride, a selective 5-HTR(2) agonist, exerted similar effects on phagocytic cells as serotonin. It can be concluded that serotonin could affect the oxidative burst of phagocytes. Responsibility for its inhibitory effects lies with both the decrease in the generation of reactive oxygen species (due to the inhibition of myeloperoxidase activity) and with direct scavenging of reactive oxygen species. The effect of serotonin on phagocytes is also partially mediated by 5-HTR(2) receptor.
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic. milanciz@ibp.cz
Milan
M
Cíz
Daniela
D
Komrsková
Lucie
L
Pracharová
Katerina
K
Okénková
Hana
H
Cízová
Aneta
A
Moravcová
Viera
V
Jancinová
Margita
M
Petríková
Antonín
A
Lojek
Radomír
R
Nosál
D004305:Dose-Response Relationship, Drug; D006801:Humans; D008163:Luminescent Measurements; D009195:Peroxidase / Q000037:antagonists & inhibitors; D010586:Phagocytes / Q000378:metabolism*; D044348:Receptors, Serotonin, 5-HT2; D016897:Respiratory Burst / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*
D044348:Receptors, Serotonin, 5-HT2; D012701:Serotonin; D009195:Peroxidase