Marc Parmentier

Université Libre de Bruxelles, Bruxelles, Brussels Capital, Belgium

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Publications (291)1553.39 Total impact

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    Marc Parmentier

    Preview · Article · Jun 2015 · Frontiers in Immunology
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    ABSTRACT: The ability of GPCRs to activate selective signaling pathways according to the conformation stabilized by bound ligands (signaling bias) is a challenging concept in the GPCR field. Signaling bias has been documented for several GPCRs, including chemokine receptors. However, most of these studies examined the global signaling bias between G protein- and arrestin-dependent pathways, leaving unaddressed the potential bias between particular G protein subtypes. Here, we investigated the coupling selectivity of chemokine receptors CCR2, CCR5 and CCR7 in response to various ligands with G protein subtypes by using BRET biosensors monitoring directly the activation of G proteins. We also compared data obtained with the G protein biosensors to those obtained with other functional readouts, such as β-arrestin-2 recruitment, cAMP accumulation and calcium mobilization assays. We showed that the binding of chemokines to CCR2, CCR5 and CCR7 activated the three Gαi subtypes (Gαi1, Gαi2 and Gαi3) and the two Gαo isoforms (Gαoa and Gαob) with potencies that generally correlate to their binding affinities. In addition, we showed that the binding of chemokines to CCR5 and CCR2 also activated Gα12, but not Gα13. For each receptor, we showed that the relative potency of various agonist chemokines was not identical in all assays, supporting the notion that signaling bias exists at chemokine receptors. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Full-text · Article · Jan 2015 · Journal of Biological Chemistry
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    ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive and irreversible respiratory failure. Validated non-invasive methods able to assess disease activity are essential for prognostic purpose as well as for the evaluation of emerging anti-fibrotic treatments. C57BL6 mice were used in a murine model of pulmonary fibrosis induced by an intra-tracheal instillation of bleomycin (control mice were instilled with a saline solution). At different times post-instillation, (18)F-FDG or (18)F-FBEM-labeled leukocytes PET-CT were performed to assess metabolic activity and leukocyte recruitment, respectively. In bleomycin-treated mice, a higher metabolic activity was measured on (18)F-FDG PET-CT scans from day 7 to day 24 post-instillation with a peak of activity measured at day 14. Of note, lung SUVmean values correlated with bleomycin doses, histological score of fibrosis, lung hydroxyproline content and weight loss. Moreover, during the inflammatory phase of the model (day 7), but not the fibrotic phase (day 23), bleomycin-treated mice present with an enhanced leukocyte recruitment as assessed by (18)F-FBEM-labeled leukocyte PET-CT. Autoradiographic analysis of lung sections and CD45 immunostaining confirm the higher and early recruitment of leukocytes in bleomycin-treated mice compared to control mice. (18)F-FDG and (18)F-FBEM-labeled leukocytes PET-CT enable to monitor metabolic activity and leukocyte recruitment in a mouse model of pulmonary fibrosis. Implications for pre-clinical evaluation of anti-fibrotic therapy are expected. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Full-text · Article · Dec 2014 · Journal of Nuclear Medicine
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    Full-text · Dataset · Jan 2014
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    ABSTRACT: Chemerin was initially described as a chemoattractant factor for leukocyte populations. More recently, the protein was also reported as an adipokine regulating adipocyte differentiation in vitro via its receptor ChemR23, and correlating with body mass index and other parameters of the metabolic syndrome in humans. The aim of the present study is to investigate the role of the chemerin-ChemR23 axis in the regulation of metabolism in vivo, using a mouse knock out model for ChemR23 in a C57Bl6 genetic background. Body weight and adipose tissue mass were not different in young animals, but became significantly higher for ChemR23 KO animals older than 12 months. Glucose tolerance was unaffected. No significant modifications of blood lipids were observed and no enhancement of inflammatory markers was seen in KO mice adipose tissue. A high fat diet did not exacerbate the obese phenotype in ChemR23 KO mice. No obvious defect in adipocyte differentiation was detected, while a marker of lipogenic activity (GPDH expression) was found elevated. In conclusion, the chemerin/ChemR23 system does not appear to play a major role in adipocyte differentiation in vivo, but intervene in adipose tissue homeostasis.
    Full-text · Article · Oct 2013 · Journal of Endocrinology
  • G Vassart · M Parmentier · F Libert · J Dumont

    No preview · Article · Apr 2013
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    ABSTRACT: Recent studies have shown that heteromerization of the chemokine receptors CCR2, CCR5 and CXCR4 is associated to negative binding cooperativity. In the present study, we build on these previous results, and investigate the consequences of chemokine receptor heteromerization with ChemR23, the receptor of chemerin, a leukocyte chemoattractant protein structurally unrelated to chemokines. We show, using BRET and HTRF assays, that ChemR23 forms homomers, and provide data suggesting that ChemR23 also forms heteromers with the chemokine receptors CCR7 and CXCR4. As previously described for other chemokine receptor heteromers, negative binding cooperativity was detected between ChemR23 and chemokine receptors, i.e. the ligands of one receptor competed for the binding of a specific tracer of the other. We also showed, using mouse bone marrow-derived dendritic cells prepared from wild-type and ChemR23 knockout mice, that ChemR23-specific ligands cross-inhibited CXCL12 binding on CXCR4 in a ChemR23-dependent manner, supporting the relevance of the ChemR23/CXCR4 interaction in native leukocytes. Finally, and in contrast to the situation encountered for other previously characterized CXCR4 heteromers, we showed that the CXCR4-specific antagonist AMD3100 did not cross-inhibit chemerin binding in cells co-expressing ChemR23 and CXCR4, demonstrating that cross-regulation by AMD3100 depends on the nature of receptor partners with which CXCR4 is co-expressed.
    Full-text · Article · Feb 2013 · PLoS ONE
  • P Vanderhaegen · S Schurmans · M Parmentier · G Vassart

    No preview · Article · Feb 2013
  • M Parmentier · P Vanderhaegen · S Schurmans · F Libert · G Vassart

    No preview · Article · Feb 2013
  • M Parmentier · F Libert · G Vassart

    No preview · Article · Feb 2013
  • Marc Parmentier
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    ABSTRACT: A new high-throughput method for monitoring G protein-coupled receptor activation is highly suited to assaying G alpha(12/13)-coupled receptors and is used to deorphanize a group of receptors activated by lysophosphatidylserine.
    No preview · Article · Oct 2012 · Nature Methods
  • M Samson · F Aubry · M Parmentier

    No preview · Article · Aug 2012
  • M Samson · F Libert · G Vassart · M Parmentier

    No preview · Article · Jul 2012

  • No preview · Article · Jul 2012
  • JC Meunier · Molereau C · J Costentin · M Parmentier · G Vassart

    No preview · Article · Jul 2012
  • M Samson · G Vassart · M Parmentier

    No preview · Article · Jul 2012
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    ABSTRACT: 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.
    Full-text · Article · Jun 2012 · PLoS ONE
  • Benjamin Bondue · Valérie Wittamer · Marc Parmentier
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    ABSTRACT: Chemerin was isolated as the natural ligand of the G protein-coupled receptor ChemR23. Chemerin acts as a chemotactic factor for leukocyte populations expressing ChemR23, particularly immature plasmacytoid dendritic cells, but also immature myeloid DCs, macrophages and natural killer cells. Chemerin is expressed by epithelial and non-epithelial cells as an inactive precursor, present at nanomolar concentrations in plasma. Processing of the precursor C-terminus is required for generating bioactive forms of chemerin. Various proteases mediate this processing, including neutrophil serine proteases and proteases from coagulation and fibrinolytic cascades. ChemR23-expressing cells are recruited in human inflammatory diseases, such as psoriasis and lupus. In animal models, both pro-inflammatory and anti-inflammatory roles of chemerin have been reported. Recently, two other receptors for chemerin were described, GPR1 and CCRL2, but their functional relevance is largely unknown. Both chemerin and ChemR23 are also expressed by adipocytes, and the emerging role of chemerin as an adipokine regulating lipid and carbohydrate metabolism is an area of intense research.
    No preview · Article · Nov 2011 · Cytokine & growth factor reviews
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    ABSTRACT: 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.
    Full-text · Article · Nov 2011 · PLoS Pathogens
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    ABSTRACT: The peptide F2L was previously characterized as a high-affinity natural agonist for the human formyl peptide receptor (FPR) 3. F2L is an acetylated 21-aa peptide corresponding with the N terminus of the intracellular heme-binding protein 1 (HEBP1). In the current work, we have investigated which proteases were able to generate the F2L peptide from its precursor HEBP1. Structure-function analysis of F2L identified three amino acids, G(3), N(7), and S(8), as the most important for interaction of the peptide with FPR3. We expressed a C-terminally His-tagged form of human HEBP1 in yeast and purified it to homogeneity. The purified protein was used as substrate to identify proteases generating bioactive peptides for FPR3-expressing cells. A conditioned medium from human monocyte-derived macrophages was able to generate bioactivity from HEBP1, and this activity was inhibited by pepstatin A. Cathepsin D was characterized as the protease responsible for HEBP1 processing, and the bioactive product was identified as F2L. We have therefore determined how F2L, the specific agonist of FPR3, is generated from the intracellular protein HEBP1, although it is unknown in which compartment the processing by cathepsin D occurs in vivo.
    Preview · Article · Jun 2011 · The Journal of Immunology

Publication Stats

26k Citations
1,553.39 Total Impact Points


  • 1986-2015
    • Université Libre de Bruxelles
      • • Institute of Interdisciplinary Research in human and molecular Biology (IRIBHM)
      • • Faculty of Medicine
      • • Department of Interdisciplinary Research
      Bruxelles, Brussels Capital, Belgium
  • 1994-2012
    • University Hospital Brussels
      Bruxelles, Brussels Capital, Belgium
  • 2008
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 1988-2007
    • Vrije Universiteit Brussel
      • Institute of Interdisciplinary Research (IRIBHM)
      Bruxelles, Brussels Capital, Belgium
    • Vanderbilt University
      • Department of Biochemistry
      Nashville, MI, United States
  • 2001
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • Università degli studi di Cagliari
      Cagliari, Sardinia, Italy
  • 1999
    • University of Lausanne
      Lausanne, Vaud, Switzerland
  • 1997
    • The Rockefeller University
      New York, New York, United States
  • 1996-1997
    • University of Pennsylvania
      • • Department of Pathology
      • • Department of Medicine
      Philadelphia, PA, United States