期刊
JOURNAL OF IMMUNOLOGY
卷 185, 期 10, 页码 5900-5906出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0901799
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资金
- Actions de Recherche Concertees de la Communaute Francaise de Belgique
- Belgian Program on Interuniversity Poles of Attraction
- Belgian State, Prime Minister's Office, Federal Service for Science, Technology and Culture
- Fonds de la Recherche Scientifique Medicale
- Fonds National de la Recherche Scientifique, Belgium
- Fonds David and Alice Van Buuren
- ATPBone project
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) (ADP beta S) induced intracellular Ca2+ 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 Ca2+ response to ADP beta S was maintained in P2Y(13)-deficient DCs, whereas it was abolished completely in P2Y(12)(-/-) DCs. ADP beta S stimulated FITC-dextran and OVA capture in murine DCs through macropinocytosis, and this effect was abolished in P2Y(12)(-/-) DCs. ADP beta S had a similar effect on FITC-dextran uptake by human monocyte-derived DCs. OVA loading in the presence of ADP beta S increased the capacity of DCs to stimulate OVA-specific T cells, whereas ADP beta S 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. The Journal of Immunology, 2010, 185: 5900-5906.
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