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Updated: Jun 17, 2026

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
Published on: December 13, 2024
Eicosanoid-induced store-operated calcium entry in dendritic cells
Kiyoshi Itagaki1, Beverly E Barton, Thomas F Murphy
1Division of Trauma, Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07101, USA.
Insights
Eicosanoids, such as leukotriene B4 and LTD4, influence dendritic cell (DC) calcium levels by depleting endoplasmic reticulum stores. This finding reveals a novel mechanism for regulating DC function and immune responses.
Area of Science:
- Immunology
- Cell Biology
- Calcium Signaling
Background:
- Eicosanoids modulate immune cells, including dendritic cells (DCs).
- Dendritic cell maturation and function are influenced by store-operated calcium entry (SOCE).
- Intracellular calcium dynamics may mediate eicosanoid effects on DCs.
Purpose of the Study:
- To investigate the impact of eicosanoids on calcium mobilization in dendritic cells.
- To determine if eicosanoids affect store-operated calcium entry (SOCE) in DCs.
- To explore the role of intracellular calcium in eicosanoid-mediated DC function.
Main Methods:
- Dendritic cells (DCs) were generated from mouse bone marrow.
- The effects of eicosanoids on intracellular calcium levels and SOCE were measured.
- RT-PCR was used to identify relevant receptors and ion channels in DCs.
Main Results:
- Leukotriene B4 (LTB4) and LTD4 depleted calcium from DC endoplasmic reticulum stores.
- Specific antagonists blocked LTB4 and LTD4-induced calcium store depletion.
- DCs express receptors for LTB4 and cysteinyl-leukotrienes, along with TRPC and STIM1 proteins involved in SOCE.
- Prostaglandin E2 (PGE2) did not affect DC calcium mobilization.
Conclusions:
- Eicosanoids exhibit distinct effects on dendritic cell calcium mobilization.
- These findings suggest a novel mechanism for regulating DC maturation via calcium signaling.
- This has significant implications for understanding immune and non-immune inflammatory processes.
Background:
Eicosanoids 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.
Methods:
DC 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 Ca(2+) mobilization.
Results:
The 5-lipoxygenase (5-LO) products leukotriene B(4) (LTB(4)) and LTD(4,) but not LTC(4), depleted Ca(2+) from DC endoplasmic reticulum stores. The specificity of LTB(4) and LTD(4) on Ca(2+) store-depletion was confirmed by the ability of the specific receptor antagonists, LY25583 and MK571, respectively, to abrogate Ca(2+) store depletion. RT-PCR demonstrated DC receptors for LTB(4) (BLT(1) and BLT(2)) and the cysteinyl-LTs (CysLT(1), CysLT(2), 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 PGE(2) had no effect on DC Ca(2+) mobilization.
Conclusions:
To our knowledge, these are the first observations of distinct effects of eicosanoids on DC Ca(2+) mobilization, which may have important implications for the regulation of DC maturation at sites of immune and non-immune inflammation.
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