Chemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury through ChemR23

Jenna L Cash, Stefania Bena, Sarah E Headland, Simon McArthur, Vincenzo Brancaleone, Mauro Perretti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)999-1007
Number of pages9
JournalEMBO Reports
Volume14
Issue number11
DOIs
Publication statusPublished - Nov 2013

Keywords

  • Animals
  • Blood Vessels
  • Cell Communication
  • Chemotactic Factors
  • Endothelial Cells
  • Humans
  • Inflammation
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Inbred C57BL
  • Microvessels
  • Myocardial Reperfusion Injury
  • Neutrophils
  • Peptide Fragments
  • Peptides
  • Receptors, Chemokine
  • Receptors, G-Protein-Coupled
  • Up-Regulation

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