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. |