Marc Parmentier

Université Libre de Bruxelles, Bruxelles, Brussels Capital Region, Belgium

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Publications (272)1562.77 Total impact

  • [Show abstract] [Hide abstract]
    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.
    The Journal of biological chemistry. 01/2015;
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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.
    Journal of Nuclear Medicine 12/2014; · 5.56 Impact Factor
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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.
    Journal of Endocrinology 10/2013; · 3.59 Impact Factor
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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.
    PLoS ONE 02/2013; 8(2):e58075. · 3.53 Impact Factor
  • Marc Parmentier
    Nature Methods 10/2012; 9(10):965-6. · 23.57 Impact Factor
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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.
    PLoS ONE 06/2012; 7(6):e40043. · 3.53 Impact Factor
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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.
    Cytokine & growth factor reviews 11/2011; 22(5-6):331-8. · 6.49 Impact Factor
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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.
    PLoS Pathogens 11/2011; 7(11):e1002358. · 8.06 Impact Factor
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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.
    The Journal of Immunology 06/2011; 187(3):1475-85. · 5.36 Impact Factor
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    ABSTRACT: Dendritic cells (DCs) have a pivotal role in the autoimmune response of systemic lupus erythematosus. Plasmacytoid DCs infiltrate the kidney of patients with lupus nephritis, but factors regulating their recruitment to the kidney are unknown. Chemerin is the recently identified natural ligand of ChemR23, a receptor highly expressed by plasmacytoid DCs. We performed immunohistochemical and immunofluorescence analysis to study the ChemR23/Chemerin axis in renal biopsies from patients with lupus nephritis. We found ChemR23-positive DCs had infiltrated the kidney tubulointerstitium in patients with severe lupus nephritis. Chemerin association with tubular epithelial cells and renal lymphatic endothelial cells was found in patients with lupus nephritis but not in normal kidneys. Proximal tubular epithelial cells produced Chemerin in vitro, which was significantly down-modulated by added tumor necrosis factor (TNF)-α and interferon-γ as measured by quantitative PCR and enzyme-linked immunosorbent assay. Interestingly, TNF-α was capable of inducing a functionally active form of renal Chemerin, resulting in an efficient transendothelial migration of plasmacytoid DCs measured in transwell systems. Thus, the ChemR23/Chemerin axis may have a role in the recruitment of DCs within the kidney in patients affected by lupus nephritis.
    Kidney International 02/2011; 79(11):1228-35. · 8.52 Impact Factor
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    ABSTRACT: We investigated possible cellular receptors for the human CXC chemokine platelet factor-4 variant/CXCL4L1, a potent inhibitor of angiogenesis. We found that CXCL4L1 has lower affinity for heparin and chondroitin sulfate-E than platelet factor-4 (CXCL4) and showed that CXCL10 and CXCL4L1 could displace each other on microvascular endothelial cells. Labeled CXCL4L1 also bound to CXCR3A- and CXCR3B-transfectants and was displaced by CXCL4L1, CXCL4, and CXCL10. The CXCL4L1 anti-angiogenic activity was blocked by anti-CXCR3 antibodies (Abs) in the Matrigel and cornea micropocket assays. CXCL4L1 application in CXCR3(-/-) or in wild-type mice treated with neutralizing anti-CXCR3 Abs, resulted in reduced inhibitory activity of CXCL4L1 on tumor growth and vascularization of Lewis lung carcinoma. Furthermore, CXCL4L1 and CXCL4 chemoattracted activated T cells, human natural killer cells, and human immature dendritic cells (DCs). Migration of DCs toward CXCL4 and CXCL4L1 was desensitized by preincubation with CXCL10 and CXCL11, inhibited by pertussis toxin, and neutralized by anti-CXCR3 Abs. Chemotaxis of T cells, natural killer cells, and DCs is likely to contribute to the antitumoral action. However, the in vivo data indicate that the angiostatic property of CXCL4L1 is equally important in retarding tumor growth. Thus, both CXCR3A and CXCR3B are implicated in the chemotactic and vascular effects of CXCL4L1.
    Blood 10/2010; 117(2):480-8. · 9.78 Impact Factor
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    ABSTRACT: SUMMARY: Rapid expansion of available data about G Protein Coupled Receptor (GPCR) dimers/oligomers over the past few years requires an effective system to organize this information electronically. Based on an ontology derived from a community dialog involving colleagues using experimental and computational methodologies, we developed the GPCR-Oligomerization Knowledge Base (GPCR-OKB). GPCR-OKB is a system that supports browsing and searching for GPCR oligomer data. Such data were manually derived from the literature. While focused on GPCR oligomers, GPCR-OKB is seamlessly connected to GPCRDB, facilitating the correlation of information about GPCR protomers and oligomers. Availability and Implementation: The GPCR-OKB web application is freely available at http://www.gpcr-okb.org
    Bioinformatics 07/2010; 26(14):1804-5. · 4.62 Impact Factor
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    ABSTRACT: It has been reported that, as well as morphine, the cannabinoid CB1 receptor agonist WIN 55,212-2 failed to induce intravenous self-administration in mutant CB1 receptor knockout (CB1−/−) mice but not in the corresponding wild type (CB1+/+) mice. To verify whether this functional interaction responsible for opioid rewarding effects was specific or could also be extended to other drugs of abuse, we have evaluated the ability of cocaine, amphetamine and nicotine to induce intravenous self-administration in both CB1−/− and CB1+/+ mice.The results showed that, contrary to morphine, the other drugs of abuse were intravenously self-administered to the same extent by both wild type and CB1−/− mice. This points to a specific role of the CB1 receptor in the opioid motivational and rewarding properties.In addition, since mesolimbic dopamine transmission is known to have a pivotal role in reward mediation, the effect of morphine on limbic dopamine release in CB1−/− and CB1+/+ mice has been investigated and compared with the effect of cocaine.Morphine did not modify dopamine release in the nucleus accumbens of CB1−/− mice whereas it dose-dependently stimulated dopamine release in the corresponding CB1+/+ mice. In contrast, cocaine increased dopamine release in both strains of mice, showing that its effect on dopamine transmission was not linked to the cannabinoid system.Taken together, our results clearly show that the CB1 receptor is essential for the expression of the behavioural and biochemical effects of morphine. This extends previous observations on a functional specific interaction between endogenous cannabinoid and opiate systems in the central mechanisms of reward.
    Pharmacy and Pharmacology Communications. 02/2010; 6(6):281 - 285.
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    ABSTRACT: Chemokine receptors constitute an attractive family of drug targets in the frame of inflammatory diseases. However, targeting specific chemokine receptors may be complicated by their ability to form dimers or higher order oligomers. Using a combination of luminescence complementation and bioluminescence resonance energy transfer assays, we demonstrate for the first time the existence of hetero-oligomeric complexes composed of at least three chemokine receptors (CCR2, CCR5, and CXCR4). We show in T cells and monocytes that negative binding cooperativity takes place between the binding pockets of these receptors, demonstrating their functional interaction in leukocytes. We also show that specific antagonists of one receptor (TAK-779 or AMD3100) lead to functional cross-inhibition of the others. Finally, using the air pouch model in mice, we show that the CCR2 and CCR5 antagonist TAK-779 inhibits cell recruitment promoted by the CXCR4 agonist SDF-1α, demonstrating that cross-inhibition by antagonists also occurs in vivo. Thus, antagonists of the therapeutically important chemokine receptors regulate the functional properties of other receptors to which they do not bind directly with important implications for the use of these agents in vivo.
    Journal of Biological Chemistry 11/2009; 284(45):31270-31279. · 4.60 Impact Factor
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    ABSTRACT: Chemerin is the ligand of the ChemR23 receptor and a chemoattractant factor for human immature dendritic cells (DCs), macrophages, and NK cells. In this study, we characterized the mouse chemerin/ChemR23 system in terms of pharmacology, structure-function, distribution, and in vivo biological properties. Mouse chemerin is synthesized as an inactive precursor (prochemerin) requiring, as in human, the precise processing of its C terminus for generating an agonist of ChemR23. Mouse ChemR23 is highly expressed in immature plasmacytoid DCs and at lower levels in myeloid DCs, macrophages, and NK cells. Mouse prochemerin is expressed in most epithelial cells acting as barriers for pathogens but not in leukocytes. Chemerin promotes calcium mobilization and chemotaxis on DCs and macrophages and these functional responses were abrogated in ChemR23 knockout mice. In a mouse model of acute lung inflammation induced by LPS, chemerin displayed potent anti-inflammatory properties, reducing neutrophil infiltration and inflammatory cytokine release in a ChemR23-dependent manner. ChemR23 knockout mice were unresponsive to chemerin and displayed an increased neutrophil infiltrate following LPS challenge. Altogether, the mouse chemerin/ChemR23 system is structurally and functionally conserved between human and mouse, and mouse can therefore be considered as a good model for studying the anti-inflammatory role of this system in the regulation of immune responses and inflammatory diseases.
    The Journal of Immunology 11/2009; 183(10):6489-99. · 5.36 Impact Factor
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    ABSTRACT: Chemokine receptors constitute an attractive family of drug targets in the frame of inflammatory diseases. However, targeting specific chemokine receptors may be complicated by their ability to form dimers or higher order oligomers. Using a combination of luminescence complementation and bioluminescence resonance energy transfer assays, we demonstrate for the first time the existence of hetero-oligomeric complexes composed of at least three chemokine receptors (CCR2, CCR5, and CXCR4). We show in T cells and monocytes that negative binding cooperativity takes place between the binding pockets of these receptors, demonstrating their functional interaction in leukocytes. We also show that specific antagonists of one receptor (TAK-779 or AMD3100) lead to functional cross-inhibition of the others. Finally, using the air pouch model in mice, we show that the CCR2 and CCR5 antagonist TAK-779 inhibits cell recruitment promoted by the CXCR4 agonist SDF-1 alpha, demonstrating that cross-inhibition by antagonists also occurs in vivo. Thus, antagonists of the therapeutically important chemokine receptors regulate the functional properties of other receptors to which they do not bind directly with important implications for the use of these agents in vivo.
    Journal of Biological Chemistry 09/2009; 284(45):31270-9. · 4.60 Impact Factor
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    ABSTRACT: The neuromodulator adenosine, acting through activation of four defined metabotropic receptors called A(1), A(2A), A(2B) and A(3,) has been proposed as an endogenous anticonvulsant. Here, the consequences of deleting the adenosine A(2A) receptor have been examined in different experimental models of epilepsy. A(2A)R KO mice were not protected against seizures originating from brainstem structures, namely electroshock-induced seizures. The intensities of seizures induced by pentylenetetrazol or pilocarpine, as well as the percentages of convulsing mice, were significantly reduced in A(2A) receptor knockout (A(2A)R KO) animals. A(2A)R KO mice exhibited reduced pentylenetetrazol-induced kindled seizures, demonstrating an important role of the A(2A) receptor in the acquisition of kindling. These data suggest that adenosine stimulating A(2A) receptors modulates excitatory neurotransmission and exacerbates limbic seizures. It is therefore suggested that adenosine A(2A) receptor antagonists might offer protection from some epileptic syndromes.
    Archiv für Experimentelle Pathologie und Pharmakologie 07/2009; 380(3):223-32. · 2.15 Impact Factor
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    ABSTRACT: Formyl peptide receptors (FPRs) are a small group of seven-transmembrane domain, G protein-coupled receptors that are expressed mainly by mammalian phagocytic leukocytes and are known to be important in host defense and inflammation. The three human FPRs (FPR1, FPR2/ALX, and FPR3) share significant sequence homology and are encoded by clustered genes. Collectively, these receptors bind an extraordinarily numerous and structurally diverse group of agonistic ligands, including N-formyl and nonformyl peptides of different composition, that chemoattract and activate phagocytes. N-formyl peptides, which are encoded in nature only by bacterial and mitochondrial genes and result from obligatory initiation of bacterial and mitochondrial protein synthesis with N-formylmethionine, is the only ligand class common to all three human receptors. Surprisingly, the endogenous anti-inflammatory peptide annexin 1 and its N-terminal fragments also bind human FPR1 and FPR2/ALX, and the anti-inflammatory eicosanoid lipoxin A4 is an agonist at FPR2/ALX. In comparison, fewer agonists have been identified for FPR3, the third member in this receptor family. Structural and functional studies of the FPRs have produced important information for understanding the general pharmacological principles governing all leukocyte chemoattractant receptors. This article aims to provide an overview of the discovery and pharmacological characterization of FPRs, to introduce an International Union of Basic and Clinical Pharmacology (IUPHAR)-recommended nomenclature, and to discuss unmet challenges, including the mechanisms used by these receptors to bind diverse ligands and mediate different biological functions.
    Pharmacological reviews 07/2009; 61(2):119-61. · 18.55 Impact Factor
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    ABSTRACT: The CC chemokine CCL14a is constitutively expressed in a large variety of tissues and its inactive proform CCL14a(1-74) circulates in high concentrations in plasma. CCL14a(1-74) is converted into CCL14a(9-74) by the proteases urokinase-type plasminogen activator and plasmin and is a highly active agonist for the chemokine receptors CCR1 and CCR5. In this study, a new CCL14a analog, CCL14a(12-74), was isolated from blood filtrate. To elucidate the functional role of the N terminus, a panel of N-terminally truncated CCL14a analogs were tested on the receptors CCR1 to CCR5 and on the human cytomegalovirus (HCMV)-encoded chemokine receptor US28. The rank order of binding affinity to these receptors and of the activation of CCR1 and CCR5-mediated intracellular Ca(2+) concentration mobilization is CCL14a(6-74)<(7-74)<(8-74)<(9-74) = (10-74)>(11-74)>(12-74). The almost identical affinities of CCL14a(7-74), CCL14a(9-74), and CCL14a(10-74) for the US28 receptor and the inhibition of US28-mediated HIV infection of 293T cells by all of the N-terminally truncated CCL14a analogs support the promiscuous nature of the viral chemokine receptor US28. In high concentrations, CCL14a(12-74) did reveal antagonistic activity on intracellular Ca(2+) concentration mobilization in CCR1- and CCR5-transfected cells, which suggests that truncation of Tyr(11) might be of significance for an efficient inactivation of CCL14a. A putative inactivation pathway of CCL14a(9-74) to CCL14a(12-74) may involve the dipeptidase CD26/dipeptidyl peptidase IV (DPPIV), which generates CCL14a(11-74), and the metalloprotease aminopeptidase N (CD13), which displays the capacity to generate CCL14a(12-74) from CCL14a(11-74). Our results suggest that the activity of CCL14a might be regulated by stringent proteolytic activation and inactivation steps.
    The Journal of Immunology 06/2009; 183(2):1229-37. · 5.36 Impact Factor

Publication Stats

19k Citations
1,562.77 Total Impact Points

Institutions

  • 1987–2013
    • Université Libre de Bruxelles
      • • Institute of Interdisciplinary Research in human and molecular Biology (IRIBHM)
      • • Faculty of Medicine
      • • Department of Interdisciplinary Research
      • • Department of Chest Medicine
      Bruxelles, Brussels Capital Region, Belgium
  • 2006–2010
    • KU Leuven
      • Department of Microbiology and Immunology
      Leuven, VLG, Belgium
  • 2009
    • Istituto di Cura e Cura a Carattere Scientifico Basilicata
      Rionero in Vulture, Basilicate, Italy
  • 1996–2009
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
    • Università degli Studi di Brescia
      • Department of Clinical and Experimental Sciences
      Brescia, Lombardy, Italy
  • 2005–2006
    • University Pompeu Fabra
      • Neuropharmacology Laboratory Research Group (Neurophar)
      Barcelona, Catalonia, Spain
  • 1995–2005
    • Free University of Brussels
      • Institute of Interdisciplinary Research (IRIBHM)
      Bruxelles, Brussels Capital Region, Belgium
  • 2001
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
  • 1996–1999
    • University of Pennsylvania
      • • Department of Pathology and Laboratory Medicine
      • • Department of Pathology
      • • Department of Medicine
      Philadelphia, PA, United States
  • 1992
    • University of Tsukuba
      Tsukuba, Ibaraki, Japan
  • 1988
    • Vanderbilt University
      • Department of Biochemistry
      Nashville, MI, United States