Serotonin upregulates the activity of phagocytosis through 5‐HT_1A receptors

Abstract

1 In this study, we investigated whether serotonin could regulate the in vitro activity of phagocytosis through 5-hydroxytryptamine or serotonin (5-HT 1A ) receptors. 2 Mouse peritoneal macrophages were cultured with serotonin and the activity of phagocytosis was assessed by the uptake of zymosan and latex particles added to the culture media. Specific binding of [ 3 H]8-OH-DPAT and immunohistochemistry using an affinity-purified anti-5-HT 1A -receptor antibody were assayed in the macrophages. In addition, we took advantage of the availability of pharmacological inhibitors of nuclear factor-kB (NF-kB) to explore its role in the regulation of the 5-HT 1A receptor. 3 Serotonin increased the in vitro activity of phagocytosis in a dose-dependent manner. The 5-HT 1A receptor agonist (7)-8-hydroxy-2-(di-n-propyl-amino)-tetralin (R(+)-8-OH-DPAT) reproduced these effects. Serotonin-or R(+)-8-OH-DPAT-induced increases in phagocytosis were blocked by the 5-HT 1A receptor antagonist WAY100635 and the NF-kB inhibitor pyrrolidinedithiocarbamate. Moreover, mouse peritoneal macrophages expressed specific binding sites for [3 H]8-OH-DPAT when cultivated in the presence of zymosan or latex beads. Immunohistochemistry confirmed the expression of the 5-HT 1A receptor protein in the macrophages. 4 These results show that serotonin can upregulate the activity of peritoneal macrophages through 5-HT 1A receptors.

A Dialogue between the Immune System and Brain, Spoken in the Language of Serotonin

“…For example in macrophages, 5-HT stimulates phagocytosis 67 of cells that contained zymosan, a component of yeast cell walls that is used to induced sterile inflammation. 68 5-HT also plays a role in enhancing the cytotoxicity of NK cells 67,69 cells in blood and lymph that are not phagocytic but promote cell lysis when stimulated. Together, these findings indicate that multiple cells of the native immune system possess the machinery to produce, store, release, and respond to 5-HT, with the overall picture being one to mobilize cells to target to, and destroy, pathogens.…”

Role of a Serotonin Precursor in Development of Gut Microvilli

“…21 The peritoneal macrophages were cultured for 24 hours, and Cy5.5 (Molecular Probes)-labeled zymosan was added to the macrophages for an hour in a final concentration of 100 g/ml. The number of zymosan particles in a cell was quantitatively determined.…”

Neuroendocrine Signaling Via the Serotonin Transporter Regulates Clearance of Apoptotic Cells

“…They found that 5-HT enhanced latex bead ingestion when cells were simultaneously exposed to small concentrations of IFN␥ but inhibited ingestion when exposed to larger concentrations. In contrast, Freire-Garabal et al (42) found that a short exposure to 5-HT increased latex bead phagocytosis by resident peritoneal macrophages from BALB/c mice. More recently Krabbe et al (43) demonstrated that 5-HT inhibits ingestion of microspheres by microglia, resident macrophages of the CNS.…”

“…Several groups have studied the effect of 5-HT on phagocytosis of targets that are unrelated to efferocytosis by murine peritoneal macrophages, such as bone marrow-derived macrophages and microglia, but the effects have been variable (42)(43)(44). We performed similar experiments using resident and TGelicited peritoneal macrophages and found that 5-HT inhibited ingestion of latex beads, but had no effect on ingestion of IgGopsonized erythrocytes through the Fc␥ receptor (Fig.…”