title: Chemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury through ChemR23.
abstract: Neutrophil activation and adhesion must be tightly controlled to prevent complications associated with excessive inflammatory responses. The role of the anti-inflammatory peptide chemerin15 (C15) and the receptor ChemR23 in neutrophil physiology is unknown. Here, we report that ChemR23 is expressed in neutrophil granules and rapidly upregulated upon neutrophil activation. C15 inhibits integrin activation and clustering, reducing neutrophil adhesion and chemotaxis in vitro. In the inflamed microvasculature, C15 rapidly modulates neutrophil physiology inducing adherent cell detachment from the inflamed endothelium, while reducing neutrophil recruitment and heart damage in a murine myocardial infarction model. These effects are mediated through ChemR23. We identify the C15/ChemR23 pathway as a new regulator and thus therapeutic target in neutrophil-driven pathologies.
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Cash
authors.forename: Stefania
authors.initials: S
authors.lastname: Bena
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Headland
authors.forename: Simon
authors.initials: S
authors.lastname: McArthur
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Brancaleone
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D019707:Receptors, Chemokine / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C102741:CMKLR1 protein, human; C486456:CMKLR1 protein, mouse; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C000589458:chemerin15 peptide, mouse