Effect of serotonin on murine macrophages: suppression of Ia expression by serotonin and its reversal by 5-HT2 serotonergic receptor antagonists.
Serotonin (5-HT), a mediator released from platelets at sites of inflammation, suppressed IFN-gamma-induced Ia expression in mouse bone marrow macrophages maintained in vitro. (Mean percent suppression = 63.9% +/- 9.2, n = 40.) This suppression was not toxic or endotoxin-related, was concentration-dependent, and occurred at the physiologic concentrations of 5-HT present at inflammatory sites. The concentration of 5-HT producing the half-maximal effect was 2.5 to 5.5 X 10(-8) M. Related compounds, dopamine, histamine, and tryptamine, were much less potent in suppressing IFN-gamma-induced Ia, with maximally suppressing concentrations more than 100-fold higher than the maximally suppressing 5-HT concentration. L-5-hydroxytryptophan (5-HTP), the most potent analog tested, was 10-fold less potent than 5-HT in suppressing Ia expression. The concentration of 5-HTP producing the half-maximal effect = 4 X 10(-7) M. 5-HT suppression of IFN-gamma-induced Ia expression was antagonized by the 5-HT2 type receptor antagonists spiperone, ketanserin, and LY53857. Concentrations of these agents resulting in 50% inhibition of the serotonin effect were 1.5 X 10(-8) M, 7.5 X 10(-8) M, and 4.5 X 10(-12) M, respectively. 5-HT was most effective in suppressing IFN-gamma-induced Ia when added early in culture simultaneously with IFN-gamma. These data provide functional evidence that 5-HT suppression of IFN-gamma-induced Ia expression is mediated through a 5-HT receptor with some characteristics of the 5-HT2 type. 5-HT may play a physiologic role at sites of inflammation as a modulator of the effects of IFN-gamma on macrophage function.
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Sternberg
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Trial
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Parker
D000818:Animals; D001853:Bone Marrow; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D005312:Fetal Blood / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008222:Lymphokines / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D008222:Lymphokines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D007371:Interferon-gamma