Reference : CLEC-2 is required for the activation of mouse platelets by bacterial DNA mimetics
Scientific congresses and symposiums : Unpublished conference/Abstract
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/183877
CLEC-2 is required for the activation of mouse platelets by bacterial DNA mimetics
English
Delierneux, Céline [Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine >]
Hego, Alexandre [Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine >]
LECUT, Christelle [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie biologique et immuno hématologie >]
Vandereyken, Maud [Université de Liège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
MUSUMECI, Lucia mailto [Centre Hospitalier Universitaire de Liège - CHU > > Centre d'oncologie >]
Rahmouni, Souad mailto [Université de Liège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
BOURS, Vincent [Centre Hospitalier Universitaire de Liège - CHU > > Génétique >]
Lancellotti, Patrizio [Université de Liège > Département des sciences cliniques > Imagerie cardiaque fonctionnelle par échographie >]
Oury, Cécile mailto [Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine >]
22-Jun-2015
Yes
No
International
ISTH 2015 Congress
du 20 au 25 Juin 2015
ISTH
Toronto
Canada
[en] Aims: To evaluate whether CpG ODNs affect platelet activation and thrombus formation via CLEC-2 and TLR9.
Methods: We incubated washed platelets or whole blood from TLR9-, MyD88- or CLEC-2- deficient mice with CpG ODNs. We performed platelet aggregometry, flow cytometric binding and platelet activation assays as well as signal transduction analyses. Thrombus formation and fibrin generation were also analyzed by intravital microscopy in mouse microcirculation upon intravenous injection of CpG ODNs.
Results: We show that CpG ODNs bind on platelet surface and are internalized. They activate platelets and induce their aggregation. TLR9- or MyD88-deficient platelets aggregated normally in response to CpG ODN. Interestingly, platelets deficient for the C-type lectin receptor CLEC-2 were unable to capture and internalize CpG ODN. CLEC-2 deficiency abolished CpG ODN-induced platelet activation and aggregation. CpG ODN stimulated CLEC-2 dependent tyrosine kinase pathway and Syk phosphorylation. In vivo, intravenously injected CpG ODN interacted with platelets adhered to laser injured arteriolar endothelia and promoted fibrin generation and thrombus growth.
Conclusion: CLEC-2 mediates CpG ODN uptake and subsequent platelet activation, independently of TLR9, which may serve an important role in the interplay between platelets and immunity.
Researchers ; Professionals
http://hdl.handle.net/2268/183877

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