The Chemerin/ChemR23 System Does Not Affect the Pro-Inflammatory Response of Mouse and Human Macrophages Ex Vivo

Macrophages constitute a major component of innate immunity and play an essential role in defense mechanisms against external aggressions and in inflammatory responses. Chemerin, a chemoattractant protein, is generated in inflammatory conditions, and recruits cells expressing the G protein-coupled receptor ChemR23, including macrophages. Chemerin was initially expected to behave as a pro-inflammatory agent. However, recent data described more complex activities that are either pro- or anti-inflammatory, according to the disease model investigated. In the present study, peritoneal macrophages were generated from WT or ChemR23−/− mice, stimulated with lipopolyssaccharide in combination or not with IFN-γ and the production of pro- (TNF-α, IL-1β and IL-6) and anti-inflammatory (IL-10) cytokines was evaluated using qRT-PCR and ELISA. Human macrophages generated from peripheral blood monocytes were also tested in parallel. Peritoneal macrophages from WT mice, recruited by thioglycolate or polyacrylamide beads, functionally expressed ChemR23, as assessed by flow cytometry, binding and chemotaxis assays. However, chemerin had no effect on the strong upregulation of cytokine release by these cells upon stimulation by LPS or LPS/IFN-γ, whatever the concentration tested. Similar data were obtained with human macrophages. In conclusion, our results rule out the direct anti-inflammatory effect of chemerin on macrophages ex vivo, described previously in the literature, despite the expression of a functional ChemR23 receptor in these cells

ChemR23 Dampens Lung Inflammation and Enhances Anti-viral Immunity in a Mouse Model of Acute Viral Pneumonia

Viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. Plasmacytoid dendritic cells play an important role in anti-viral immunity, and these cells were recently shown to express ChemR23, the receptor for the chemoattractant protein chemerin, which is expressed by epithelial cells in the lung. Our aim was to determine the role played by the chemerin/ChemR23 system in the physiopathology of viral pneumonia, using the pneumonia virus of mice (PVM) as a model. Wild-type and ChemR23 knock-out mice were infected by PVM and followed for functional and inflammatory parameters. ChemR23−/− mice displayed higher mortality/morbidity, alteration of lung function, delayed viral clearance and increased neutrophilic infiltration. We demonstrated in these mice a lower recruitment of plasmacytoid dendritic cells and a reduction in type I interferon production. The role of plasmacytoid dendritic cells was further addressed by performing depletion and adoptive transfer experiments as well as by the generation of chimeric mice, demonstrating two opposite effects of the chemerin/ChemR23 system. First, the ChemR23-dependent recruitment of plasmacytoid dendritic cells contributes to adaptive immune responses and viral clearance, but also enhances the inflammatory response. Second, increased morbidity/mortality in ChemR23−/− mice is not due to defective plasmacytoid dendritic cells recruitment, but rather to the loss of an anti-inflammatory pathway involving ChemR23 expressed by non-leukocytic cells. The chemerin/ChemR23 system plays important roles in the physiopathology of viral pneumonia, and might therefore be considered as a therapeutic target for anti-viral and anti-inflammatory therapies

Contribution à l'étude du pouvoir antioxidant et des propriétés immunomodulatrices d'un composé à groupement thiol, le nacystelyn

Doctorat en sciences pharmaceutiquesinfo:eu-repo/semantics/nonPublishe

Contribution à l'étude du pouvoir antioxidant et des propriétés immunomodulatrices d'un composé à groupement thiol, le nacystelyn

Doctorat en sciences pharmaceutiquesinfo:eu-repo/semantics/nonPublishe

Inhibitory effects of several thiol-containing drugs on erythrocyte oxidative damages investigated with an improved assay system

The involvement of oxygen-derived free radicals and other oxidant species in numerous physiopathological processes makes it necessary to develop suitable analytical systems to study their effects and also to assess the antioxidant activity of endogenous and exogenous compounds. In this respect, the properties of three selected thiol-containing drugs (Captopril, N-acetylcystiene and its lysine salt Nacystelyn, a newly developed mucoactive agent) and of reference compounds were examined in a lipid peroxidation model using human red blood cells (RBC) as biological substrate. The thermolabile azo-compound 2,2′-azobis-2-amidinopropane dihydrochloride (AAPH) served for the generation of an oxidative stress and the determination of the extent of RBC haemolysis was recorded. Experimental conditions were developed and optimised to ensure the stability and reproducibility of the system and to establish complete dose-response relationships in order to determine relevant pharmacological parameters. Actually, the AAPH/haemolysis system shrewdly combined with a procedure to measure the extent of haemolysis in which all common haemoglobin derivatives released following haemolysis are converted to cyanomethaemoglobin, allowed the assessment of the antioxidant activity of most investigated drugs. Precision was also improved by considering readings at 50% haemolysis (T50). The following sequence was obtained for the antioxidant properties of investigated drugs: uric acid > Trolox > ascorbic acid > N-acetylcysteine ∼ Nacystelyn > Captopril ≫ L-lysine. © 2002 Elsevier Science B.V. All rights reserved.info:eu-repo/semantics/publishe

Application de techniques de peroxydation d'érythrocytes intacts à l'évaluation de l'activité antioxydante de molécules médicamenteuses

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

PET-CT with 18F-FDG and 18F-FBEM-labeled leukocytes for metabolic activity and leukocyte recruitment monitoring in a mouse model of pulmonary fibrosis

0info:eu-repo/semantics/publishe

Peroxidation of intact erythrocyte membranes by two initiators for the assessment of the antioxidant activity of drugs: application to therapeutically-relevant thiols

info:eu-repo/semantics/nonPublishe

Influence du pH sur le pouvoir antioxydant de molécules médicamenteuses évalué par un modèle de peroxydation d'érythrocytes intacts

info:eu-repo/semantics/nonPublishe

Développement et optimalisation d'une méthode d'étude de l'activité antioxydante de divers thiols basée sur l'utilisation d'érythrocytes intacts

info:eu-repo/semantics/nonPublishe