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Publication : Role of the P2Y12 receptor in the modulation of murine dendritic cell function by ADP.

First Author  Ben Addi A Year  2010
Journal  J Immunol Volume  185
Issue  10 Pages  5900-6
PubMed ID  20952684 Mgi Jnum  J:165783
Mgi Id  MGI:4838463 Doi  10.4049/jimmunol.0901799
Citation  Ben Addi A, et al. (2010) Role of the P2Y12 receptor in the modulation of murine dendritic cell function by ADP. J Immunol 185(10):5900-6
abstractText  The effects of ADP on the biology of dendritic cells have been studied much less than those of ATP or adenosine. In this study, we showed that adenosine-5'-O-(2-thiodiphosphate) (ADPbetaS) induced intracellular Ca(2+) transients in murine dendritic cells (DCs). This effect was abolished by AR-C69931MX, a dual P2Y(12) and P2Y(13) receptor antagonist. RT-PCR experiments revealed the expression of both P2Y(12) and P2Y(13) mRNA in DCs. The Ca(2+) response to ADPbetaS was maintained in P2Y(13)-deficient DCs, whereas it was abolished completely in P2Y(12)(-/-) DCs. ADPbetaS stimulated FITC-dextran and OVA capture in murine DCs through macropinocytosis, and this effect was abolished in P2Y(12)(-/-) DCs. ADPbetaS had a similar effect on FITC-dextran uptake by human monocyte-derived DCs. OVA loading in the presence of ADPbetaS increased the capacity of DCs to stimulate OVA-specific T cells, whereas ADPbetaS had no effect on the ability of DCs to stimulate allogeneic T cells. Moreover, after immunization against OVA, the serum level of anti-OVA IgG1 was significantly lower in P2Y(12)(-/-) mice than that in wild-type controls. In conclusion, we have shown that the P2Y(12) receptor is expressed in murine DCs and that its activation increased Ag endocytosis by DCs with subsequent enhancement of specific T cell activation.
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