Cooperation between the Fc epsilonR1 and formyl peptide receptor signaling pathways in RBL(FPR) cells: the contribution of receptor-specific Ca2+ mobilization responses.

RBL(FPR) mast cells express the tyrosine kinase-coupled IgE receptor, Fc epsilonR1, and the G-protein-coupled formyl peptide receptor, FPR. Fc epsilonR1 crosslinking causes Ca2+ stores release, Ca2+ influx, Ins(1,4,5)P3 production and secretion. FPR ligation also mobilizes Ca2+, but without measurable Ins(1,4,5)P3 production or secretion. Co-stimulating the FPR and Fc epsilonR1 induces more Ins(1,4,5)P3 production and secretion than Fc epsilonR1 cross-linking alone. Costimulation also produces more rapid and sustained Ca2+ responses than are generated by Fc epsilonR1 activation alone. We identified multiple differences between the FPR- and Fc epsilonR1-coupled Ca2+ responses, including a more rapid Ca2+ spike response to FPR ligation; intracellular Ca2+ stores that are empty following Fc epsilonR1 crosslinking but partially full following FPR activation; a more sustained Ca2+ influx response to Fc epsilonR1 crosslinking; and the immediate inhibition of stimulated Ca2+ influx by FPR antagonists but not by monovalent ligand that terminates Fc epsilonR1 crosslinking. We hypothesize that the interaction of receptor-specific Ca2+ mobilization pathways contributes to the FPR-mediated potentiation of Fc epsilonR1-coupled secretion.