Neutrophil-mediated maturation of chemerin: a link between innate and adaptive immunity.
Dendritic cells and macrophages are professional APCs that play a central role in initiating immune responses, linking innate and adaptive immunity. Chemerin is a novel chemoattractant factor that specifically attracts APCs through its receptor ChemR23. Interestingly, chemerin is secreted as a precursor of low biological activity, prochemerin, which upon proteolytic removal of a C-terminal peptide, is converted into a potent and highly specific agonist of its receptor. Given the fact that APCs are often preceded by polymorphonuclear cells (PMN) in inflammatory infiltrates, we hypothesized that PMN could mediate chemerin generation. We demonstrate here that human degranulated PMNs release proteases that efficiently convert prochemerin into active chemerin. The use of specific protease inhibitors allowed us to identify the neutrophil serine proteases cathepsin G and elastase as responsible for this process. Mass spectrometry analysis of processed prochemerin showed that each protease generates specifically a distinct form of active chemerin, differing in their C terminus and initially identified in human inflammatory fluids. These findings strongly suggest that bioactive chemerin generation takes place during the early stages of inflammation, underscoring the functional contribution of chemerin as a bridge between innate and adaptive immunity.
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels, Belgium.
Valérie
V
Wittamer
Benjamin
B
Bondue
Aude
A
Guillabert
Gilbert
G
Vassart
Marc
M
Parmentier
David
D
Communi
D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D001665:Binding Sites; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D015550:Cell Degranulation; D018925:Chemokines / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins; D019272:Leukocyte Elastase / Q000378:metabolism; D018448:Models, Immunological; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012697:Serine Endopeptidases / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D011480:Protease Inhibitors; C478630:RARRES2 protein, human; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase