Background: Mast cell-released chemical mediators such as histamine, leukotriene (LT) C4 and prostaglandin (PG) D2 lead to the onset of allergic disorders. ATP provided from glycolysis is essential for histamine release and LTC4 secretion from mast cells upon FcΕRI cross-linking, indicating that glucose is a primary environmental factor for mast cell activation. In this study, we investigated whether increases in concentrations of glucose in culture media affect the activation of bone marrow-derived mouse mast cells (BMMCs) upon FcΕRI cross-linking. Methods: BMMCs were cultured in RPMI-1640 supplemented with varying concentrations (5.5, 11, 16.5, 22, 27.5 and 33 mM) of D-glucose for 3 h, or 1, 3 or 7 days. D-Mannitol was added to the medium containing 5.5 mMD-glucose for osmotic control. After culturing, these cells were sensitized with anti-TNP IgE and then stimulated with TNP-BSA. Results: We found that long-term culture (7 days) of BMMCs with 33 mMD-glucose increases the FcΕRI-dependent release of β-hexosaminidase and LTC4 without affecting surface expression levels of FcΕRI, intracellular ATP levels or calcium signaling. Biochemical analyses demonstrated that FcΕRI-dependent phosphorylation of cytosolic phospholipase A2 (cPLA2) at the Ser505 residue was significantly increased by culturing with 33 mM glucose. Conclusions: Taken together, our data suggest that glucose can augment FcΕRI-mediated mast cell activation, particularly the degranulation response and LTC4 secretion after prolonged culture of mast cells with high-glucose medium. Moreover, it is suggested that increased phosphorylation of cPLA2 at the Ser505 residue contributes to the enhancement of LTC4 secretion.

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