Eicosanoid-Induced Store-Operated Calcium Entry in Dendritic Cells

BackgroundEicosanoids are generally recognized to exert potent immunomodulatory properties, including effects on T cell, antigen-presenting cell (APC), and dendritic cell (DC) maturation and function. Since DC maturation and function may also be regulated by store-operated calcium entry (SOCE), we hypothesized that the effects of eicosanoids on DC function may in part be regulated through changes in intracellular calcium.MethodsDC derived from the bone marrow of male Balb/ByJ mice cultured for 7 d in the presence of granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) were used to study the effects of eicosanoids on SOCE and the resulting Ca2+ mobilization.ResultsThe 5-lipoxygenase (5-LO) products leukotriene B4 (LTB4) and LTD4, but not LTC4, depleted Ca2+ from DC endoplasmic reticulum stores. The specificity of LTB4 and LTD4 on Ca2+ store-depletion was confirmed by the ability of the specific receptor antagonists, LY25583 and MK571, respectively, to abrogate Ca2+ store depletion. RT-PCR demonstrated DC receptors for LTB4 (BLT1 and BLT2) and the cysteinyl-LTs (CysLT1, CysLT2, and GPR17). We also detected transient receptor potential canonical (TRPC) 1, 2, 4, and 6 and stromal interaction molecule 1 (STIM1) on CD11c+ DCs, suggesting these proteins also participate in DC SOCE. In contrast, the cyclooxygenase (CO) metabolite PGE2 had no effect on DC Ca2+ mobilization.ConclusionsTo our knowledge, these are the first observations of distinct effects of eicosanoids on DC Ca2+ mobilization, which may have important implications for the regulation of DC maturation at sites of immune and non-immune inflammation.