A5021541509- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nuclear Structure and Function
- RNA Research and Splicing
- Immune cells in cancer
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- Eicosanoids and Hypertension Pharmacology
- PARP inhibition in cancer therapy
- Nitric Oxide and Endothelin Effects
- Heme Oxygenase-1 and Carbon Monoxide
- Liver Disease and Transplantation
- Genomics and Chromatin Dynamics
- Drug-Induced Hepatotoxicity and Protection
- Neuroinflammation and Neurodegeneration Mechanisms
- Food Allergy and Anaphylaxis Research
- Advanced Glycation End Products research
- Ubiquitin and proteasome pathways
- Extracellular vesicles in disease
- Mast cells and histamine
- Circadian rhythm and melatonin
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Pneumocystis jirovecii pneumonia detection and treatment
- Telomeres, Telomerase, and Senescence
- Chemokine receptors and signaling
- Drug-Induced Adverse Reactions
Queen Mary University of London
2018-2024
William Harvey Research Institute
2018-2024
RELX Group (United States)
2020
Centre National de la Recherche Scientifique
2015-2020
Inserm
2012-2020
Délégation Paris 7
2015-2019
Sorbonne Paris Cité
2015-2019
Centre de Recherche sur l'Inflammation
2015-2019
Université Paris Cité
2015-2019
Neutrophils require directional cues to navigate through the complex structure of venular walls and into inflamed tissues. Here we applied confocal intravital microscopy analyze neutrophil emigration in cytokine-stimulated mouse cremaster muscles. We identified differential non-redundant roles for chemokines CXCL1 CXCL2, governed by their distinct cellular sources. was produced mainly TNF-stimulated endothelial cells (ECs) pericytes supported luminal sub-EC crawling. Conversely, neutrophils...
Aging is associated with dysregulated immune functions. Here, we investigated the impact of age on neutrophil diapedesis. Using confocal intravital microscopy, found that in aged mice, neutrophils adhered to vascular endothelium inflamed tissues but exhibited a high frequency reverse transendothelial migration (rTEM). This retrograde breaching by was governed enhanced production chemokine CXCL1 from mast cells localized at endothelial cell (EC) junctions. Increased EC expression atypical...
The migration of neutrophils from the blood circulation to sites infection or injury is a key immune response and requires breaching endothelial cells (ECs) that line inner aspect vessels. Unregulated neutrophil transendothelial cell (TEM) pathogenic, but molecular basis its physiological termination remains unknown. Here, we demonstrated ECs venules in inflamed tissues exhibited robust autophagic was aligned temporally with peak trafficking strictly localized EC contacts. Genetic ablation...
Increased microvascular permeability to plasma proteins and neutrophil emigration are hallmarks of innate immunity key features numerous inflammatory disorders. Although neutrophils can promote leakage, the impact vascular on trafficking is unknown. Here, through application confocal intravital microscopy, we report that permeability-enhancing stimuli caused a significant frequency reverse transendothelial cell migration (rTEM). Furthermore, mice with selective defect in enhancement...
Significance: Despite their intrinsic cytotoxic properties, mounting evidence indicates that reactive oxygen species (ROS) physiologically produced by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) of epithelial cells (NOX1, dual oxidase [DUOX]2) and phagocytes (NOX2) are critical for innate immune response homeostasis intestinal mucosa. However, dysregulated ROS production could be a driving factor in inflammatory bowel diseases (IBDs). Recent Advances: In addition...
Background: Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder characterized by premature aging and death mainly because of myocardial infarction, stroke, or heart failure. The disease provoked progerin, variant lamin A expressed in most differentiated cells. Patients look healthy at birth, symptoms typically emerge the first second year life. Assessing reversibility progerin-induced damage relative contribution specific cell types critical to determining potential benefits late...
Cirrhosis is commonly accompanied by impaired defense functions of polymorphonuclear leucocytes (PMNs), increased patient susceptibility to infections, and hepatocellular carcinoma (HCC). PMN antimicrobial activity dependent on a massive production reactive oxygen species (ROS) nicotinamide adenine dinucleotide phosphate (NADPH) 2 (NADPH oxidase 2; NOX2), termed respiratory burst (RB). Rapamycin, an antagonist mammalian target rapamycin (mTOR), may be used in the treatment HCC transplanted...
Objective Cirrhosis downregulates phagocyte oxidant production via their antibacterial superoxide-generating system, NADPH oxidase (NOX2) and increases patients’ susceptibility to infection mortality rate. To explore novel biochemical parameters that explain infections, we investigated the expression of NOX2 partners in neutrophils patients with severe alcoholic cirrhosis have provided a approach restore superoxide capacity blood. Design Neutrophils were isolated from decompensated...
Hutchinson–Gilford progeria syndrome (HGPS, progeria) is a rare genetic disease characterized by premature aging and death in childhood for which there were no approved drugs its treatment until last November, when lonafarnib obtained long-sought FDA approval. However, the benefits of patients are limited, highlighting need new therapeutic strategies. Here, we validate enzyme isoprenylcysteine carboxylmethyltransferase (ICMT) as target with development series potent inhibitors this that...
Hutchinson–Gilford progeria syndrome (HGPS) is a rare disease caused by the expression of progerin, mutant protein that accelerates aging and precipitates death. Given atherosclerosis complications are main cause death in progeria, here, we investigated whether progerin-induced prevented HGPSrev-Cdh5-CreERT2 HGPSrev-SM22α-Cre mice with progerin suppression endothelial cells (ECs) vascular smooth muscle (VSMCs), respectively. were undistinguishable from HGPSrev ubiquitous expression, contrast...
Abstract The nuclear lamina (NL) lines the envelope (NE) to maintain structure in metazoan cells. major NL components, lamins contribute protection against NE rupture induced by mechanical stress. Lamin A (LA) and a short form of splicing variant lamin C (LC) are diffused from nucleoplasm sites immortalized mouse embryonic fibroblasts (MEFs). LA localization is significantly slow weak compared with LC, but underlying mechanism remains unknown. In this study, wild-type (WT),...
ABSTRACT Upon inflammation, leukocytes extravasate through endothelial cells. When they in a paracellular manner, it is generally accepted that neighbouring cells physically disconnect to open cell-cell junctions, allowing cross. carefully examining we found partial membrane overlap of beyond VE-cadherin distribution. These overlaps are regulated by actin polymerization and, although marked by, do not require PECAM-1, nor VE-cadherin. Neutrophils prefer wider as exit sites. Detailed 3D...
Abstract The nuclear lamina (NL) lines the envelope (NE) to maintain structure in metazoan cells. major NL components, lamins contribute protection against NE rupture induced by mechanical stress. Lamin A (LA) and a short form of splicing variant lamin C (LC) are diffused from nucleoplasm sites immortalized mouse embryonic fibroblasts (MEFs). LA localization is significantly slow weak compared LC because its relatively small pool nucleoplasm, but precise mechanism remains unknown. In this...
ABSTRACT Progerin is a mutant prelamin A variant that causes Hutchinson–Gilford progeria syndrome (HGPS, progeria), rare genetic disease characterized by premature aging and death in childhood. Although several therapeutic approaches have been explored experimental models, clinical trials shown very limited benefits HGPS patients. Here, we describe the development of UCM-13207, new potent inhibitor isoprenylcysteine carboxylmethyltransferase (ICMT) reduces progerin nuclear accumulation...
Abstract Superoxide anion production by the phagocyte NADPH oxidase plays a crucial role in host defenses and inflammatory reaction. The is composed of cytosolic components (p40phox, p47phox, p67phox, Rac1/2) membrane flavocytochrome b558, which two proteins: p22phox gp91phox/NOX2. stabilization gp91phox phagocytes also docking site for p47phox during activation. In current study, we have used yeast two-hybrid approach to identify unknown partners p22phox. Using C-terminal region as bait...