Nitric oxide inhibits IgE-mediated degranulation of mast cells and is the principal intermediate in IFN-gamma-induced suppression of exocytosis.

Abstract

IFN-gamma regulates various aspects of rodent peritoneal mast cell function, including mediator release, cell growth, TNF-alpha-mediated cytotoxicity, and MHC class II expression. We investigated whether the suppressive action of IFN-gamma on IgE/Ag-mediated degranulation of mast cells is mediated via synthesis of nitric oxide. Incubation of mouse peritoneal cells with L-NMMA, an inhibitor of nitric oxide synthase, or in medium lacking the nitric oxide precursor L-arginine reversed the inhibitory effect of IFN-gamma on Ag-induced serotonin release. Furthermore, the nitric oxide donors sodium nitroprusside and S-nitrosoglutathione inhibited degranulation, and this effect was direct, since it was seen equally on purified and unfractionated mast cells and occurred independently of IFN-gammaR expression. Additional experiments revealed that accessory cells in peritoneal cell populations were the principal target for the action of IFN-gamma and the main source of nitric oxide; the cytokine was more potent on unfractionated compared with purified mast cells, and IFN-gamma induced detectable nitrite production in mixed peritoneal cells, but not in purified mast cells. These studies show that IFN-gamma induces nitric oxide production in peritoneal cell populations, and that synthesized nitric oxide directly inhibits the IgE-mediated secretory function of mast cells. The activation of nitric oxide-producing cells in the tissue microenvironment may be important in the control of mast cell-dependent allergic reactions.

Oxytocin Attenuates Sympathetic Innervation with Inhibition of Cardiac Mast Cell Degranulation in Rats after Myocardial Infarction

“…For example, mast cell degranulation is regulated by intracellular calcium release from the endoplasmic reticulum and activation of protein kinase C (PKC), which depends on the activation of G-protein-coupled receptors (GPCRs) on the mast cell surface (Kimura et al, 1998;Nguyen et al, 2002;Kuehn and Gilfillan, 2007). Eastmond NC et al reported that NO directly inhibited the IgE-mediated secretory function of mast cells (Eastmond et al, 1997). OT promotes NO synthesis by cardiac myocytes and dorsal root ganglion (Jankowski et al, 2010;Gutkowska et al, 2014, Gong et al, 2015.…”

Oxytocin attenuates sympathetic innervation with inhibition of cardiac mast cell degranulation in rats post myocardial infarction

“…For example, mast cell degranulation is regulated by intracellular calcium release from the endoplasmic reticulum and the activation of protein kinase C (PKC), which depends on the activation of G-protein-coupled receptors (GPCRs) on the mast cell surface (28-30). Eastmond NC et al reported that NO directly inhibited the IgEmediated secretory function of mast cells (31). OT promotes NO synthesis by cardiac myocytes (11,32) and dorsal root ganglion(DRG) neurons synthesize NO (33).…”

Generation, Isolation, and Maintenance of Rodent Mast Cells and Mast Cell Lines

“…The number of mast cells routinely obtained is always greater in ovalbumin (OVA)-sensitized rats. The total cell yield from mice ranges from 1 to 3 × 10 6 mixed peritoneal cells, 3 to 6 × 10 5 of which will be mast cells (Coleman et al, 1993;Eastmond et al, 1997).…”