Ca2+and Protein Kinase C Signaling for Histamine and Sulfidoleukotrienes Released from Human Cultured Mast Cells

Abstract

Human cultured mast cells (HCMC) release histamine and sulfidoleukotrienes (LTs) upon IgE-FcϵRI-mediated mast cell activation. We analyzed the Ca2+and PKC signaling in HCMC and compared it to that in rodent mast cells. In HCMC, after IgE-mediated stimulation, an elevation of [Ca2+]iand PKC translocation to the membrane fraction was observed. As concerns Ca2+signaling, 1) IgE-mediated histamine and LTs release was abolished after Ca2+depletion, and the reconstitution of Ca2+recovered the release of histamine and LTs. As regards PKC signaling, 1) staurosporine inhibited IgE-mediated mediator release. 2) PKC-downregulated mast cells did not release histamine and LTs. A23187 and PMA synergistically potentiated the activation of extracellular-regulated kinase and synergistically induced histamine and LTs release. These results demonstrated that HCMC might be useful for analysis of the signal transduction pathway for mediator release, such as histamine and LTs.