Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids.
Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity. ChemR23 is an orphan G protein-coupled receptor related to chemokine receptors, which is expressed specifically in these cell types. Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids. Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor. Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42-p44 MAP kinases, through the Gi class of heterotrimeric G proteins. Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens. Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner. Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs.
Wittamer
Valérie
V
Institut de Recherche en Biologie Humaine et Moléculaire, ULB Campus Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium.
Franssen
Jean-Denis
JD
Vulcano
Marisa
M
Mirjolet
Jean-François
JF
Le Poul
Emmanuel
E
Migeotte
Isabelle
I
Brézillon
Stéphane
S
Tyldesley
Richard
R
Blanpain
Cédric
C
Detheux
Michel
M
Mantovani
Alberto
A
Sozzani
Silvano
S
Vassart
Gilbert
G
Parmentier
Marc
M
Communi
David
D
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D018925:Chemokines / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D019707:Receptors, Chemokine / Q000378:metabolism*
C102741:CMKLR1 protein, human; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D019707:Receptors, Chemokine; D002118:Calcium