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Potential role of the peroxidase-dependent metabolism of serotonin in lowering the polymorphonuclear leukocyte
S Salman-Tabcheh1, M C Guérin, J Torreilles
1INSERM unité 58, Montpellier, France.
Abstract:
Serotonin (5-hydroxytryptamine, 5-HT) significantly and dose-dependently suppressed the luminol-enhanced chemiluminescence (CL) signal generated by polymorphonuclear leukocytes (PMN) activated with phorbol myristate acetate (PMA), but did not modify either lucigenin-enhanced CL or the reduction of superoxide dismutase-inhibitable cytochrome c. Moreover, stimulation of PMNs previously incubated with 5-HT resulted in a threefold increase in 5-HT equivalents bound to the proteins of PMN. The addition of catalase or sodium azide substantially reduced this binding. The present results suggest that 5-HT metabolism is mediated by H2O2 and myeloperoxidase (MPO) released by activated PMNs. Hence 5-HT could lower the bactericidal function of these cells by competition with hypochlorite formation from halides and MPO/H2O2.
Insights
Serotonin (5-hydroxytryptamine, 5-HT) suppresses immune cell signaling and function. This suggests 5-HT may reduce the bacteria-fighting capacity of polymorphonuclear leukocytes (PMNs).
Area of Science:
- Immunology
- Biochemistry
- Cellular Biology
Background:
- Polymorphonuclear leukocytes (PMNs) are critical immune cells involved in the inflammatory response.
- Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter with known immunomodulatory effects.
- The precise mechanisms by which 5-HT influences PMN function are not fully understood.
Purpose of the Study:
- To investigate the effect of serotonin (5-HT) on the chemiluminescence (CL) and oxidative metabolism of activated PMNs.
- To explore the interaction and metabolism of 5-HT within PMNs.
- To elucidate the potential impact of 5-HT on the bactericidal functions of PMNs.
Main Methods:
- Measurement of luminol- and lucigenin-enhanced chemiluminescence (CL) in PMNs stimulated with phorbol myristate acetate (PMA).
- Assay for superoxide production via the reduction of cytochrome c.
- Quantification of 5-HT binding to PMN proteins and assessment of the role of hydrogen peroxide (H2O2) and myeloperoxidase (MPO) using catalase and sodium azide.
Main Results:
- Serotonin (5-HT) significantly suppressed luminol-enhanced CL in PMA-activated PMNs in a dose-dependent manner.
- 5-HT did not affect lucigenin-enhanced CL or superoxide production.
- Incubation with 5-HT increased its binding to PMN proteins, a process inhibited by catalase and sodium azide, indicating mediation by H2O2 and MPO.
Conclusions:
- Serotonin (5-HT) metabolism within activated PMNs is mediated by hydrogen peroxide (H2O2) and myeloperoxidase (MPO).
- The findings suggest that 5-HT may impair the bactericidal activity of PMNs by interfering with hypochlorite formation.
- This interaction highlights a potential mechanism by which 5-HT modulates innate immune responses.