The Journal of Experimental Medicine
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Published 6 October 2003. doi:10.1084/jem.20030382
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© Rockefeller University Press, 0022-1007/2003/10/977 $5.00
The Journal of Experimental Medicine, Volume 198, Number 7, 977-985

Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids

Valérie Wittamer1, Jean-Denis Franssen2, Marisa Vulcano3, Jean-François Mirjolet1, Emmanuel Le Poul2, Isabelle Migeotte1, Stéphane Brézillon2, Richard Tyldesley4, Cédric Blanpain1, Michel Detheux2, Alberto Mantovani3,5, Silvano Sozzani3,6, Gilbert Vassart1, Marc Parmentier1 and David Communi1

1 Institut de Recherche en Biologie Humaine et Moléculaire, B-1070 Brussels, Belgium
2 Euroscreen s.a., B-6041 Gosselies, Belgium
3 Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milan, Italy
4 Micromass Ltd., Manchester M23 9LZ, United Kingdom
5 Department of General Pathology, University of Milan, 20123 Milan, Italy
6 Section of General Pathology and Immunology, University of Brescia, 25123 Brescia, Italy

Address correspondence to Marc Parmentier, Institut de Recherche en Biologie Humaine et Moléculaire, ULB Campus Erasme, 808 Route de Lennik, Brussels B-1070, Belgium. Phone: 32-2-5554171; Fax: 32-2-5554655; email: mparment{at}ulb.ac.be

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.

Key Words: orphan receptor • dendritic cells • macrophages • chemotaxis • proteolytic processing


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