References of "Lecut, Christelle"
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See detailSepsis prediction in critically ill patients by platelet activation markers on ICU admission: a prospective pilot study
LAYIOS, Nathalie ULg; Delierneux, Céline ULg; Hego, Alexandre ULg et al

in Intensive Care Medicine Experimental (in press)

Background: Platelets have been involved in both surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with ... [more ▼]

Background: Platelets have been involved in both surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with predisposition to sepsis in critical illness remains unknown. The aim of this work was to identify platelet markers that could predict sepsis occurrence in critically ill injured patients. Results: This single-center, prospective, observational, 7-month study was based on a cohort of 99 non-infected adult patients admitted to ICUs for elective cardiac surgery, trauma, acute brain injury and post-operative prolonged ventilation and followed up during ICU stay. Clinical characteristics and severity score (SOFA) were recorded on admission. Platelet activation markers, including fibrinogen binding to platelets, platelet membrane P-selectin expression, plasma soluble CD40L, and platelet-leukocytes aggregates were assayed by flow cytometry at admission and 48h later, and also at the time of sepsis diagnosis (Sepsis-3 criteria) and 7 days later for sepsis patients. Hospitalization data and outcomes were also recorded. Of the 99 patients, 19 developed sepsis after a median time of 5 days. SOFA at admission was higher; their levels of fibrinogen binding to platelets (platelet-Fg) and of D-dimers were significantly increased compared to the other patients. Levels 48h after ICU admission were no longer significant. Platelet-Fg % was an independent predictor of sepsis (P = 0.030). By ROC curve analysis cutoff points for SOFA (AUC=0.85) and Platelet-Fg (AUC=0.75) were 8 and 50%, respectively. The prior risk of sepsis (19%) increased to 50% when SOFA was above 8, to 46% when Platelet-Fg was above 50%, and to 87% when both SOFA and Platelet-Fg were above their cutoff values. By contrast, when the two parameters were below their cutoffs, the risk of sepsis was negligible (3.8%). Patients with sepsis had longer ICU and hospital stays and higher death rate. Conclusion: In addition to SOFA, platelet-bound fibrinogen levels assayed by flow cytometry within 24h of ICU admission help identifying critically ill patients at risk of developing sepsis. [less ▲]

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See detailTargeting of C-type lectin-like receptor 2 or P2Y12 for the prevention of platelet activation by immunotherapeutic CpG oligodeoxynucleotides
Delierneux, Céline ULg; Donis, Nathalie ULg; servais, laurence et al

in Journal of Thrombosis and Haemostasis (2017), 15(5), 983-997

Background: Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (CpG ODNs) display potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment ... [more ▼]

Background: Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (CpG ODNs) display potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment. Unexpectedly, a recent study indicates that CpG ODNs activate human platelets via the immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptor glycoprotein VI. Objective: To further analyze the mechanisms of CpG ODN-induced platelet activation and identify potential inhibitory strategies. Methods: In vitro analyses were performed on human and mouse platelets, and on cell lines expressing platelet ITAM receptors. CpG ODN platelet activating effects were evaluated in a mouse model of thrombosis. Results: We demonstrated platelet uptake of CpG ODNs, resulting in platelet activation and aggregation. The C-type lectin-like receptor 2 (CLEC-2) expressed in DT40 cells bound CpG ODNs. CpG ODN uptake did not occur in CLEC-2-deficient mouse platelets. Inhibition of human CLEC-2 with a blocking antibody inhibited CpG ODN-induced platelet aggregation. CpG ODNs caused CLEC-2 dimerization, and provoked its internalization. They induced dense granule release before the onset of aggregation. Accordingly, pretreating platelets with apyrase, or inhibiting P2Y12 with cangrelor or clopidogrel prevented CpG ODN platelet activating effect. In vivo, intravenously injected CpG ODN interacted with platelets adhered to mouse injured endothelium, and promoted thrombus growth, which was inhibited by CLEC-2 deficiency or by clopidogrel. Conclusions: CLEC-2 and P2Y12 are required for CpG ODN-induced platelet activation and thrombosis and might be targeted to prevent adverse events in patients at risk. [less ▲]

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See detailEccentric training for tendon healing after lesion: a rat model
Kaux, Jean-François ULg; Libertiaux, Vincent ULg; Leprince, Pierre ULg et al

in American Journal of Sports Medicine (2017), 45(6), 1440-1446

BACKGROUND:The tendon is a dynamic entity that remodels permanently. Platelet-rich plasma (PRP) injection has been shown to have a beneficial effect on tendon healing after lesion in rats. Furthermore ... [more ▼]

BACKGROUND:The tendon is a dynamic entity that remodels permanently. Platelet-rich plasma (PRP) injection has been shown to have a beneficial effect on tendon healing after lesion in rats. Furthermore, eccentric exercise seems to improve the mechanical quality of the tendon. HYPOTHESIS:A combination of PRP injection and eccentric training might be more effective than either treatment alone. STUDY DESIGN:Controlled laboratory study. METHODS:Adult male rats were anesthetized, an incision was performed in the middle of their left patellar tendon and an injection of physiological fluid (PF) or homologous PRP was randomly made at the lesion level. The rats were then divided into 2 groups: the eccentric group, undergoing eccentric training 3 times a week, and the untrained group, without any training. Thus, 4 groups were compared. After 5 weeks, the tendons were removed and their ultimate tensile strength and energy were measured. Tendons were frozen for proteomic analyses when all biomechanical tests were completed. Statistical analysis was performed with linear mixed effect models. RESULTS:No significant difference was found between the treatments using PF injection or PRP injection alone. However, the value of the ultimate tensile force at rupture was increased by 4.5 N (108% of control, P = .006) when eccentric training was performed. An intragroup analysis revealed that eccentric training significantly improved the ultimate force values for the PRP group. Proteomic analysis revealed that eccentric training led to an increase in abundance of several cytoskeletal proteins in the PF group, while a decrease in abundance of enzymes of the glycolytic pathway occurred in the PRP treated groups, indicating that this treatment might redirect the exercise-driven metabolic plasticity of the tendon. CONCLUSION: Eccentric training altered the metabolic plasticity of tendon and led to an improvement of injured tendon resistance regardless of the treatment injected (PF or PRP). CLINICAL RELEVANCE:This study demonstrates the necessity of eccentric rehabilitation and training in cases of tendon lesion regardless of the treatment carried out. [less ▲]

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See detailP2X1 ion channel is critical for vascular integrity in inflammation
Wéra, Odile ULg; Delierneux, Céline; Servais, Laurence ULg et al

Poster (2016, November)

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See detailP2X1 ion channel is critical for vascular integrity in inflammation
Wéra, Odile ULg; Delierneux, Céline; Hego, Alexandre ULg et al

Conference (2016, September)

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See detailEfficacy of the RemoweLL cardiotomy reservoir for fat and leucocyte removal from shed mediastinal blood: a randomized controlled trial.
LAGNY, Marc-Gilbert ULg; GOTHOT, André ULg; HANS, Grégory ULg et al

in Perfusion (2016)

Efficacy of the RemoweLL cardiotomy reservoir for Fat and Leucocyte removal from shed mediastinal blood: a randomized controlled trial. ABSTRACT (176 words) Introduction Re-transfusion of lipid particles ... [more ▼]

Efficacy of the RemoweLL cardiotomy reservoir for Fat and Leucocyte removal from shed mediastinal blood: a randomized controlled trial. ABSTRACT (176 words) Introduction Re-transfusion of lipid particles and activated leucocytes with shed mediastinal blood (SMB) can aggravate cardiopulmonary bypass-associated inflammation and increase the embolic load. This study evaluated the fat and leucocyte removal capacity of the RemoweLL cardiotomy reservoir. Methods Forty-five patients undergoing elective on-pump cardiac surgery were randomly allocated to filtration of SMB using the RemoweLL or the Admiral cardiotomy reservoir. The primary outcome was the drop in leucocytes and lipid particles obtained with the two filters. The effect of the filters on other blood cells and inflammatory mediators such as myeloperoxidase (MPO) was also assessed. Results The RemoweLL cardiotomy filter removed 16.5 % of the leucocytes (P < 0.001) while no significant removal of leucocytes was observed with the Admiral (P = 0.48). The percentage reductions in lipid particles were similar in the two groups (26% vs 23 %, P = 0.2). Both filters similarly affected the level of MPO (P = 0.71). Discussion The RemoweLL filter more effectively removed leucocytes from SMB than the Admiral. It offered no advantage in term of lipid particle clearance. [less ▲]

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See detailRole of inflammatory- and growth factors in the pathophysiology of gestational diabetes-related complications in neonates
Guffins, Amandine; FARHAT, Nesrine ULg; GKIOUGKI, Evangelia ULg et al

in Belgian Journal of Paediatrics (2016), 18(1), 82

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See detailCLEC-2 is required for the activation of mouseplatelets by bacterial DNA mimetics
Delierneux, Céline ULg; Hego, Alexandre ULg; LECUT, Christelle ULg et al

Conference (2015, June 22)

Background: Short nuclease-resistant phosphorothioate synthetic CpG motif-bearing oligonucleotides (CpG ODNs) mimicking bacterial DNA display potent immunostimulatory activity and are therefore being used ... [more ▼]

Background: Short nuclease-resistant phosphorothioate synthetic CpG motif-bearing oligonucleotides (CpG ODNs) mimicking bacterial DNA display potent immunostimulatory activity and are therefore being used in clinical trials as vaccine adjuvants. Cellular uptake and activation depends on the interaction of CpG ODNs with the C-type lectin receptor DEC-205 and subsequent stimulation of the Toll-like receptor 9 (TLR9) and myeloid differentiation primary response 88 (MyD88) signaling cascade. Platelets express TLR9, MyD88, and the C-type lectin-like receptor 2 (CLEC-2). However, the impacts of CpG ODNs on platelet function have been elusive. 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 deficiencyabolished 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. [less ▲]

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See detailCLEC-2 is required for the activation of mouse platelets by bacterial DNA mimetics
Delierneux, Céline ULg; Hego, Alexandre ULg; LECUT, Christelle ULg et al

Conference (2015, June 22)

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 ... [more ▼]

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. [less ▲]

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See detailQuelle place pour le test de génération de thrombine au sein du laboratoire de biologie clinique?
LECUT, Christelle ULg; PETERS, Pierre ULg; MASSION, Paul ULg et al

in Annales de Biologie Clinique (2015), 73(2), 137-149

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See detailReflections about the optimisation of the treatment of tendinopathies with PRP
Kaux, Jean-François ULg; Bouvard, Marc; LECUT, Christelle ULg et al

in Muscles, Ligaments and Tendons Journal (2015), 5(1 (eCollection 2015 Jan-Mar)), 1-4

Background: platelet-rich plasma (PRP) infiltration represents a recent therapy for chronic tendinopathies. However, in the literature, this treatment remains controversial. Purpose: we suggest some ideas ... [more ▼]

Background: platelet-rich plasma (PRP) infiltration represents a recent therapy for chronic tendinopathies. However, in the literature, this treatment remains controversial. Purpose: we suggest some ideas for improving this treatment. Methods: these suggestions were based on a review of published studies and our clinical experience. Conclusion: optimizing the technique for PRP collection is paramount. Different risk factors must be corrected before infiltration and chronic tendinopathies must be carefully selected. Finally, post-infiltration rehabilitation remains absolutely critical. Standardization of the use of PRP remains necessary in order to optimize the results. [less ▲]

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See detailDUSP3 Phosphatase Deficiency or Inhibition Limit Platelet Activation and Arterial Thrombosis
Musumeci, Lucia ULg; Kuijpers, Marijke; Gilio, Karen et al

in Circulation (2015), 131(7), 656-68

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet ... [more ▼]

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet activation is of importance for the development of improved therapies. Recently, protein tyrosine phosphatases (PTPs) have emerged as critical regulators of platelet function. Methods and Results This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated through the collagen receptor glycoprotein VI (GPVI) and the C-type lectin-like receptor 2 (CLEC-2). DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism, compared to wild-type mice, and showed severely impaired thrombus formation upon ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of PLCγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen and CLEC-2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. Conclusions DUSP3 plays a selective and essential role in collagen- and CLEC-2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a PTP, implicated in platelet signaling, has been targeted with a small-molecule drug. [less ▲]

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