References of "Delierneux, Céline"
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See detailRasa3 Controls Megakaryocyte Rap1 Activation, Integrin Signaling and Differentiation into Proplatelet
Molina Ortiz, Patricia ULg; Polizzi, Séléna; Ramery, Eve ULg et al

in PLoS Genetics (2014), 10(6), 1004420

Rasa3 is a GTPase activating protein of the GAP1 family which targets Ras and Rap1. Ubiquitous Rasa3 catalytic inactivation in mouse results in early embryonic lethality. Here, we show that Rasa3 ... [more ▼]

Rasa3 is a GTPase activating protein of the GAP1 family which targets Ras and Rap1. Ubiquitous Rasa3 catalytic inactivation in mouse results in early embryonic lethality. Here, we show that Rasa3 catalytic inactivation in mouse hematopoietic cells results in a lethal syndrome characterized by severe defects during megakaryopoiesis, thrombocytopenia and a predisposition to develop preleukemia. The main objective of this study was to define the cellular and the molecular mechanisms of terminal megakaryopoiesis alterations. We found that Rasa3 catalytic inactivation altered megakaryocyte development, adherence, migration, actin cytoskeleton organization and differentiation into proplatelet forming megakaryocytes. These megakaryocyte alterations were associated with an increased active Rap1 level and a constitutive integrin activation. Thus, these mice presented a severe thrombocytopenia, bleeding and anemia associated with an increased percentage of megakaryocytes in the bone marrow, bone marrow fibrosis, extramedular hematopoiesis, splenomegaly and premature death. Altogether, our results indicate that Rasa3 catalytic activity controls Rap1 activation and integrin signaling during megakaryocyte differentiation in mouse. [less ▲]

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See detailCompetitive interaction of a synthetic polycation (PDMAEMA) to human platelets and erythrocytes
Flebus, Luca ULg; Lombart, François ULg; martinez, Lucia et al

Poster (2013, October)

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See detailStudy of the specific interaction between fluorescent PDMAEMA and Platelets compared to Erythrocytes
Flebus, Luca ULg; Lombart, François ULg; Martinez, Lucia et al

Poster (2013, June 18)

Nowadays synthetic polymers provide more and more functionalities in the biomedical world, in particular as part of medical devices and drug delivery systems. Looking for new applications in the ... [more ▼]

Nowadays synthetic polymers provide more and more functionalities in the biomedical world, in particular as part of medical devices and drug delivery systems. Looking for new applications in the cardiovascular field, our attention has been focused on the well-known poly(2-(dimethylamino)ethyl methacrylate polymer (PDMAEMA). This synthetic polycation has particularly been studied as a potential DNA carrier to promote cell transfection. However and surprisingly enough relative few studies have been published in order to better understand its hemoreactivity under a free form (thus not based on “PolyElectrolyte Complex”), but also its biodistribution and clearance kinetics. In order to facilitate the in vitro and in vivo monitoring of this polycation and especially to follow its reactivity with whole blood we have labeled it with fluorescein adopting a new chemical route of synthesis. After its thorough purification and full-characterization (NMR, SEC, fluorescent spectroscopy), we followed its interaction with erythrocytes and platelets using flow cytometry. Dose-response curves were established in whole blood and within incubation times ranging between 5 min to 3 h. Considering the largest area and more negative Zeta potential developed by red blood cells compared to platelets, we initially hypothesized that RBC should interact more quickly and efficiently with the polycation. Unexpectedly, platelets presented a higher affinity for the polycation with a saturation binding curve whilst a linear profile was observed for the erythrocyte adsorption curve. Aggregometry analyses also revealed this phenomenon, although displaying a weaker effect in whole blood compared to washed platelets. Ongoing research seeks to understand the molecular mechanism of interaction of this polymer with platelets. [less ▲]

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See detailOverexpression of CD39 in mouse airways promotes bacteria induced inflammation
Theatre, Emilie ULg; Frederix, Kim; Guilmain, William et al

in Journal of Immunology (2012), 189(4), 1966-1974

In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of ... [more ▼]

In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of inflammation because accelerated ATP metabolism occurs in chronic inflammatory lung diseases.We sought to determine whether constant elevated CD39 activity in lung epithelia is sufficient to cause inflammation and whether this affects the response to acute LPS or Pseudomonas aeruginosa exposure. We generated transgenic mice overexpressing human CD39 under the control of the airway-specific Clara cell 10-kDa protein gene promoter. Transgenic mice did not develop any spontaneous lung inflammation. However, intratracheal instillation of LPS resulted in accelerated recruitment of neutrophils to the airways of transgenic mice. Macrophage clearance was delayed, and the amounts of CD8+ T and B cells were augmented. Increased levels of keratinocyte chemoattractant, IL-6, and RANTES were produced in transgenic lungs. Similarly, higher numbers of neutrophils and macrophages were found in the lungs of transgenic mice infected with P. aeruginosa, which correlated with improved bacteria clearance. The transgenic phenotype was partially and differentially restored by coinstillation of P2X1 or P2X7 receptor antagonists or of caffeine with LPS. Thus, a chronic increase of epithelial CD39 expression and activity promotes airway inflammation in response to bacterial challenge by enhancing P1 and P2 receptor activation. [less ▲]

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See detailATP-gated P2X1 ion channels protect from endotoxemia by dampening neutrophil activation
Lecut, Christelle ULg; Faccinetto, Céline ULg; Delierneux, Céline ULg et al

in Journal of Thrombosis and Haemostasis [=JTH] (2012), 10(3), 453-65

Background: In sepsis, extracellular ATP, secreted by activated platelets and leukocytes, may contribute to the crosstalk between hemostasis and inflammation. Previously, we showed that, in addition to ... [more ▼]

Background: In sepsis, extracellular ATP, secreted by activated platelets and leukocytes, may contribute to the crosstalk between hemostasis and inflammation. Previously, we showed that, in addition to their role in platelet activation, ATP-gated P2X1 ion channels are involved in promoting neutrophil chemotaxis. <br />Objectives: To elucidate the contribution of P2X1 ion channels to sepsis and associated disturbance of hemostasis. <br />Methods: We used P2X1-/- mice in a model of lipopolysaccharide (LPS)-induced sepsis. Hemostasis and inflammation parameters were analysed together with outcome. Mechanisms were further studied ex vivo using mouse and human blood or isolated neutrophils and monocytes. <br />Results: P2X1-/- mice were more susceptible to LPS-induced shock than wild-type mice despite normal cytokine production. Plasma levels of thrombin-antithrombin complexes were higher, thrombocytopenia was worsened and whole blood coagulation time was markedly reduced, pointing to aggravated hemostasis disturbance in the absence of P2X1. However, whole blood platelet aggregation occurred normally and P2X1-/- macrophages displayed normal levels of total tissue factor activity. We found that P2X1-/- neutrophils produced higher amounts of reactive oxygen species. Increased amounts of myeloperoxidase were released in the blood of LPS-treated P2X1-/- mice, and circulating neutrophils and monocytes expressed higher levels of CD11b. Neutrophil accumulation into the lungs was also significantly augmented, as was lipid peroxidation in the liver. Desensitization of P2X1 ion channels led to increased activation of human neutrophils and enhanced formation of platelet-leukocyte aggregates. [less ▲]

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