Platelets are required for enhanced activation of the endothelium and fibrinogen in a mouse thrombosis model of APS

Antiphospholipid syndrome (APS) is defined by thrombosis, fetal loss, and the presence of antiphospholipid antibodies, including anti-beta 2-glycoprotein-1 autoantibodies (anti-beta 2GP1) that have a direct role in the pathogenesis of thrombosis in vivo. The cellular targets of the anti-beta 2GP1autoantibody/beta 2GP1complex in vivo were studied using a laser-induced thrombosis model of APS in a live mouse and human anti-beta 2GP1 autoantibodies affinity-purified from APS patients. Cell binding of fluorescently labeled beta 2GP1 and anti-beta 2GP1 autoantibodies revealed their colocalization on the platelet thrombus but not the endothelium. Anti-beta 2GP1 autoantibodies enhanced platelet activation, monitored by calcium mobilization, and endothelial activation, monitored by intercellular adhesion molecule-1 expression. When eptifibatide was infused to block platelet thrombus formation, enhanced fibrin generation and endothelial cell activation were eliminated. Thus, the anti-beta 2GP1 autoantibody/beta 2GP1 complex binds to the thrombus, enhancing platelet activation, and platelet secretion leads to enhanced endothelium activation and fibrin generation. These results lead to a paradigm shift away from the concept that binding of the anti-beta 2GP1 autoantibody/beta 2GP1 complex activates both endothelial cells and platelets toward one in which activation of platelets in response to anti-beta 2GP1 autoantibody/beta 2GP1 complex binding leads to subsequent enhanced endothelium activation and fibrin generation

Infographie : utilisation des PRP en traumatologie sportive. Recommandations professionnelles de la Société française de traumatologie du sport Infographic : Use of platelet-rich plasma in sports medicine. Guidelines from the French Society of Sports Traumatology

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PHYSIOPATHOLOGY OF HEREDITARY XEROCYTOSIS: PIEZO1 GAIN OF FUNCTION MUTATIONS IMPACT HEMOGLOBIN OXYGEN AFFINITY

22nd Congress of the European-Hematology-Association, Madrid, SPAIN, JUN 22-25, 2017International audienc

PHYSIOPATHOLOGY OF HEREDITARY XEROCYTOSIS: PIEZO1 GAIN OF FUNCTION MUTATIONS IMPACT HEMOGLOBIN OXYGEN AFFINITY

22nd Congress of the European-Hematology-Association, Madrid, SPAIN, JUN 22-25, 2017International audienc

Efficacy and safety of high ration HVWF/FVIII concentrate (VONCENTO (R)) for the treatment of bleeding epidodes in patients with WITH VON WILLEBRAND disease :s: the OPALE French experience

International audienc

Soluble Siglec-5 associates to PSGL-1 and displays anti-inflammatory activity

International audienceInteractions between endothelial selectins and the leukocyte counter-receptor PSGL1 mediates leukocyte recruitment to inflammation sites. PSGL1 is highly sialylated, making it a potential ligand for Siglec-5, a leukocyte-receptor that recognizes sialic acid structures. Binding assays using soluble Siglec-5 variants (sSiglec-5/C4BP and sSiglec-5/Fc) revealed a dose- and calcium-dependent binding to PSGL1. Pre-treatment of PSGL1 with sialidase reduced Siglec-5 binding by 79 ± 4%. In confocal immune-fluorescence assays, we observed that 50% of Peripheral Blood Mononuclear Cells (PBMCs) simultaneously express PSGL1 and Siglec-5. Duolink-proximity ligation analysis demonstrated that PSGL1 and Siglec-5 are in close proximity (<40 nm) in 31 ± 4% of PBMCs. In vitro perfusion assays revealed that leukocyte-rolling over E- and P-selectin was inhibited by sSiglec-5/Fc or sSiglec-5/C4BP, while adhesion onto VCAM1 was unaffected. When applied to healthy mice (0.8 mg/kg), sSiglec-5/C4BP significantly reduced the number of rolling leukocytes under basal conditions (10.9 ± 3.7 versus 23.5 ± 9.3 leukocytes/field/min for sSiglec-5/C4BP-treated and control mice, respectively; p = 0.0093). Moreover, leukocyte recruitment was inhibited over a 5-h observation period in an in vivo model of TNFalpha-induced inflammation following injection sSiglec-5/C4BP (0.8 mg/kg). Our data identify PSGL1 as a ligand for Siglec-5, and soluble Siglec-5 variants appear efficient in blocking PSGL1-mediated leukocyte rolling and the inflammatory response in general

HEREDITARY XEROCYTOSIS: CLINICAL AND BIOLOGICAL PRESENTATION AT DIAGNOSIS IN A RETROSPECTIVE SERIES OF 103 PATIENTS

22nd Congress of the European-Hematology-Association, Madrid, SPAIN, JUN 22-25, 2017International audienc