Alpha7-nicotinic acetylcholine receptors involve the imidacloprid-induced inhibition of IgE-mediated rat and human mast cell activation

Although our recent study indicated that imidacloprid, a widely used neonicotinoid insecticide, inhibited IgE-mediated rat mast cell RBL-2H3 activation, little information is available on the relationship between imidacloprid and IgE-mediated human mast cell activation, and the inhibition mechanism still remains unclear. In the present work, the IgE-sensitized RBL-2H3 cells and human basophilic cell KU812 were incubated with imidacloprid or methyllycaconitine (MLA, the antagonist of alpha 7-nAChRs) prior to the treatment of imidacloprid, followed by challenging the cells with dinitrophenyl-human serum albumin and b-lactoglobulin, respectively. The allergic mediator release, Ca2+ influx in cells, cPLA2 activity, the phosphorylation contents of PLC-gamma and NF-kB in Fc epsilon RI signaling pathway were tested. The results indicated that imidacloprid could suppress the production of allergic mediators, Ca2+ mobilization, cPLA2 activity and the expression of the phosphorylated antibodies of PLC-gamma and NF-kB in the RBL-2H3 and KU812 cells. Moreover, an IgE-dependent passive cutaneous anaphylaxis model was used to determine whether alpha 7-nAChRs involved the suppressive effects of imidacloprid in vivo. It was shown that MLA alleviated the imidacloprid-induced inhibition on the absorbance value of vascular extravasation in mice. It is the first time it has been demonstrated that alpha 7-nAChRs involve the inhibitory effects of imidacloprid on the IgE-mediated activation of mast cells.