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

Abstract

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.

Trafficking properties of plasmacytoid dendritic cells in health and disease

“…ChemR23 is expressed by antigenpresenting cells, such as MDCs, PDCs and macrophages, and by blood monocytes and NK cells [55,58,92]. In contrast to other chemotactic receptors, human ChemR23 maps to chromosome 12, and shows little homology with other receptors of the same family (e.g.…”

Differential Patterns of Serum Concentration and Adipose Tissue Expression of Chemerin in Obesity: Adipose Depot Specificity and Gender Dimorphism

“…Chemerin, a recently discovered circulating chemokine, exerts its actions through cell surface receptors termed chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), or chemokine (C-C motif) receptor-like 2 (CCRL2) (Barnea et al, 2008;Cash et al, 2008;Wittamer et al, 2003;Zabel et al, 2008). Later studies characterized chemerin as an adipokine with a potential role in regulating adipocyte development in vitro and metabolic functions, such as glucose and lipid metabolism, in adipose tissue (Goralski et al, 2007).…”

Staphylococcus aureus-Derived Staphopain B, a Potent Cysteine Protease Activator of Plasma Chemerin

“…Although it is attached to the cell surface, CX3CL1 acts as a cell adhesion molecule, but after proteolytic cleavage, it functions as a soluble chemokine (5,6). Finally, recent advances reveal the potential for proteases to activate chemoattractants (7,8).…”