Ca²⁺ influx-mediated histamine synthesis and IL-6 release in mast cells activated by monomeric IgE

We previously demonstrated that histamine synthesis is drastically induced upon sensitization with an anti-DNP IgE clone, SPE-7, in IL-3-dependent mouse bone marrow derived mast cells (BMMC). We found that Ca²⁺ mobilization induced by SPE-7 exhibited a similar profile to the capacitative Ca²⁺ entry evoked by thapsigargin. Potentials for activation of mast cells were found to vary between different IgE clones, and a monovalent hapten, DNP-lysine, suppressed the activation induced by SPE-7. Ca²⁺ mobilization induced by SPE-7 was suppressed potently by the specific store-operated Ca²⁺ channel inhibitor, SK&F 96365, but not at all by Ca²⁺ channel inhibitors with more broad spectrum, La³⁺ and Gd³⁺, whereas the Ca²⁺ mobilization induced by Ag stimulation was suppressed by these inhibitors. Ca²⁺ mobilization was also induced by SPE-7 in in vitro differentiated mast cells, although the increases in histamine synthesis and IL-6 release were smaller than those in BMMC. These results suggest that Ca²⁺ influx operated by a distinct mechanism from that in Ag stimulation is essential for increased histamine synthesis and IL-6 release in mast cells.