Les plaquettes dans les réactions inflammatoires : maintien de l'intégrité vasculaire et régulation des neutrophiles

Abstract : Platelets are crucial players in hemostasis and immune responses. They intervene at various stages of inflammatory reactions. Our objectives were : (i)to characterize platelet mechanisms responsible for the prevention of inflammatory bleeding, which differs from trauma-induced bleeding, and (ii)to characterize the determinants of the regulation of neutrophil cytotoxic activities by platelets. In vivo, in an immune complex-mediated cutaneous inflammation, we demonstrated the role of glycoprotein (GP) VI in the prevention of inflammatory bleeding caused by neutrophils. Our results suggest that GPVI has a protective effect, independent of platelet aggregation, by a mechanical action associated to an activation of the ITAM (Immunoreceptor tyrosine-based activation motif)-based signaling pathway. In contrast, in an acute pulmonary inflammatory model, the ITAM receptors GPVI and CLEC-2 (C-type lectin-like receptor 2) were not required while the absence of platelet GPIb led to inflammatory bleeding. In vitro, we showed that physical interactions between neutrophils and endothelial cells are major determinants that guide the regulatory action of platelets towards neutrophil cytotoxic activities. In conclusion, our results contribute to a better understanding of platelet functions in inflammatory reactions, a necessary first step for future therapeutic applications of antiplatelet agents.
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Angèle Gros. Les plaquettes dans les réactions inflammatoires : maintien de l'intégrité vasculaire et régulation des neutrophiles. Hématologie. Université Sorbonne Paris Cité, 2017. Français. ⟨NNT : 2017USPCC288⟩. ⟨tel-02276662⟩

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