A5040384607- Platelet Disorders and Treatments
- Heparin-Induced Thrombocytopenia and Thrombosis
- Cell Adhesion Molecules Research
- Blood groups and transfusion
- Blood Coagulation and Thrombosis Mechanisms
- Antiplatelet Therapy and Cardiovascular Diseases
- Blood disorders and treatments
- Blood properties and coagulation
- Complement system in diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Monoclonal and Polyclonal Antibodies Research
- Venous Thromboembolism Diagnosis and Management
- Proteoglycans and glycosaminoglycans research
- Protease and Inhibitor Mechanisms
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cellular Mechanics and Interactions
- Hematopoietic Stem Cell Transplantation
- Renal cell carcinoma treatment
- Peripheral Neuropathies and Disorders
- Biochemical and Structural Characterization
- Autoimmune Bullous Skin Diseases
- Pancreatic function and diabetes
- Hemophilia Treatment and Research
- Patient-Provider Communication in Healthcare
- Neuroinflammation and Neurodegeneration Mechanisms
Sorbonne Paris Cité
2013-2025
Université Paris Cité
2010-2025
Inserm
2009-2025
Weizmann Institute of Science
2025
Innovations Thérapeutiques en Hémostase
2021
Biomécanique et Bioingénierie
2021
Université de Technologie de Compiègne
2021
Hôpital Européen Georges-Pompidou
2008-2021
Platod (France)
2016-2021
Délégation Paris 5
2008-2019
Objective: The inability to regulate the inflammatory response initiated upon infection leads severe sepsis, characterized by widespread microvascular injury and thrombosis, organ ischemia, dysfunction. A disintegrin-like metalloprotease with thrombospondin type 1 repeats (ADAMTS)-13 regulates primary hemostasis proteolyzing von Willebrand factor (VWF). Decreased ADAMTS-13 has been reported in disseminated intravascular coagulation due sepsis. present study investigates whether...
Abstract We present a new, rapid method for producing blood platelets in vitro from cultured megakaryocytes based on microfluidic device. This device consists wide array of VWF-coated micropillars. Such pillars act as anchors megakaryocytes, allowing them to remain trapped the and subjected hydrodynamic shear. The combined effect anchoring shear induces elongation finally their rupture into proplatelets. process was observed with different origins found be robust. original bioreactor design...
A significant challenge in cell biology is to uncover the function of uncharacterized proteins. Surprisingly a quarter proteome still poorly understood even most well studied model organisms. Systematic methodologies, including use tagged protein collections, have emerged as powerful approach address this gap. Despite availability proteome-wide collections featuring various fused proteins, impact tag size on highlighted need for using minimally disruptive tags functional genomic studies. To...
We have recently shown that von Willebrand factor (vWF) binds to endothelial and fibroblastic extracellular matrixes (ECM) in a dose-dependent, specific, saturable way. To localize the domain on vWF subunit responsible for this interaction, purified proteolytic fragments of were compared their ability inhibit 125I-vWF binding ECM. A tryptic dimeric fragment 116 kD (T116), extending from amino acid (aa) residues 449 728, produced significant inhibition In contrast, P34 (aa 1-272), SpI...
We have determined the rate constants of inactivation factor Xa and thrombin by antithrombin III/heparin during process prothrombin activation. The second-order constant inhibition alone III as using synthetic peptide substrate S-2337 was found to be 1.1 X 10(6) M-1 min-1. Factor in activation mixtures that contained prothrombin, either saturating amounts Va or phospholipid (20 mol % dioleoylphosphatidylserine/80 dioleoylphosphatidylcholine, 10 microM), inhibited with a essentially same: 1.2...
Hematopoietic stem cells (HSC) differentiate into megakaryocytes (MK), whose function is to release platelets. Attempts improve in vitro platelet production have been hampered by the low amplification of MK. Providing HSC with an optimal three-dimensional (3D) architecture may favor MK differentiation mimicking some crucial functions bone marrow structure. To this aim, porous hydrogel scaffolds were used study from as well production. Flow cytometry, qPCR and perfusion studies showed that 3D...
The inhibitory properties of a panel snake-venom-derived RGD (Arg-Gly-Asp) proteins, including the disintegrins kistrin, elegantin and albolabrin, neurotoxin homologue dendroaspin, were investigated in platelet-adhesion assay using three immobilized ligands glycoprotein IIb-IIIa complex (alpha IIb beta 3), namely fibrinogen, fibronectin von Willebrand factor (vWF). snake-venom proteins preferentially inhibited adhesion ADP-treated platelets to one or more ligands. Kistrin dendroaspin...
During the past 10 years, we have found renin-secreting renal juxtaglomerular cell tumors in three hypertensive patients (two women, one man, aged 22, 69, and 21 respectively). The major chemical biological findings revealed association of severe hypertension with hypokalemia increased plasma renin activity aldosterone. diagnosis such is difficult, two were followed up for four five years respectively before undergoing surgery. pharmacological blockade system by various agents...
During sepsis, von Willebrand factor (VWF) is abundantly secreted; the main mechanism regulating its size involves specific proteolysis by metalloprotease ADAMTS-13.To determine whether ADAMTS-13 consumption due to binding to, and/or cleavage, of VWF contributes decrease during sepsis and abrogating or enhancing activity influences outcome.ADAMTS-13 was evaluated in a model induced cecum ligature puncture (CLP) wild-type Vwf(-/-) mice. Sepsis outcome studied those mice Adamts-13(-/-)...
Colorectal cancer (CRC) mass screening has been implemented in France since 2008. Participation rates remain too low. The objective of this study was to test if the implementation a training course focused on communication skills among general practitioners (GP) would increase delivery gaiac faecal occult blood and CRC participation target population each participating GP. A cluster randomised controlled trial conducted with GP's practice as unit. GPs from practices control group were asked...
von Willebrand disease type 2B (VWD-type 2B) is characterized by gain-of-function mutations of factor (vWF) that enhance its binding to platelet glycoprotein Ibα and alter the protein's multimeric structure. Patients with VWD-type display variable extents bleeding associated macrothrombocytopenia sometimes thrombopathy. Here, we addressed molecular mechanism underlying severe both in a knockin murine model for introducing p.V1316M mutation Vwf gene patient bearing this mutation. We provide...
Abstract von Willebrand disease (VWD)-type 2B is characterized by gain-of-function mutations in the factor (VWF) A1-domain, leading to increased affinity for its platelet-receptor, glycoprotein Ibα. We engineered first knock-in (KI) murine model VWD-type introducing p.V1316M mutation VWF. Homozygous KI-mice replicated human with macrothrombocytopenia (platelet counts reduced 55%, platelet volume 44%), circulating platelet-aggregates and a severe bleeding tendency. Also, vessel occlusion was...
Abstract Blood platelets are essential for controlling hemostasis. They released by megakaryocytes (MKs) located in the bone marrow, upon extension of cytoplasmic protrusions into lumen marrow sinusoids. Their number increases postpulmonary capillaries, suggesting a role oxygen gradient thrombopoiesis (ie, platelet biogenesis). In this study, we show that initiation from human mature MKs was enhanced under hyperoxia or during pro-oxidant treatments, whereas antioxidants dampened it....
The highly negatively charged membrane sialoglycoprotein leukosialin, CD43, is shed during neutrophil activation. This generally thought to enhance cell adhesion. We here describe two novel consequences of this shedding, activation by phorbol esters or chemoattractants after TNF-α priming. CD43 proteolysis was investigated Western blotting, using a polyclonal antibody intracellular domain. Our data emphasize the importance juxtamembranous cleavage about 50% molecules cathepsin G. Indeed, it...
Abstract α9β1 is the main β1 integrin of human activated neutrophils; and α9β1/VCAM-1 interactions participate to neutrophilrolling on endothelial cells. Neutrophil expression contribution cell adhesion were revisited in this study. α5β1 appeared here as integrins expressed membrane resting platelet-depleted neutrophils—α6β1 representing <15% α2β1 undetectable. activation slightly enhanced α5 expression, did not change α6, but resulted a two- threefold increase α9β1, which then became...
It is established that proplatelets are formed from mature megakaryocytes (MK) as intermediates before platelet production. Recently, the presence of was described in blood incubated static conditions. We have previously demonstrated and proplatelet formation upregulated by MK exposure to high shear rates (1800 s(-1)) on immobilized von Willebrand factor (VWF). The purpose present study investigate whether VWF involved regulation terminal production blood. To this end, Vwf (-/-) mice, a...