Eicosanoid-induced store-operated calcium entry in dendritic cells.
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.
Itagaki
Kiyoshi
K
Division of Trauma, Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07101, USA.
Barton
Beverly E
BE
Murphy
Thomas F
TF
Taheri
Sean
S
Shu
Ping
P
Huang
Hosea
H
Jordan
Mark L
ML
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D039521:CD11c Antigen / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015777:Eicosanoids / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000378:metabolism; D017998:Leukotriene D4 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010641:Phenotype; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels / Q000378:metabolism
D039521:CD11c Antigen; D015220:Calcium Channels; D015777:Eicosanoids; D008562:Membrane Glycoproteins; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; D007975:Leukotriene B4; D017998:Leukotriene D4; D002118:Calcium