[Characterization of new chemoattractant agents in leukocytes]

G protein-coupled receptors constitute one of the largest gene families in mammals. About a hundred orphan receptors still exist, for which the ligands and functions are unknown. We have recently identified the natural ligands of two orphan receptors expressed in dendritic cells and monocytes/macrophages. Chemerin, product of the gene Tig-2, was characterized as the ligand of the chemR23 receptor. The protein is synthesized as an inactive precursor, prochemerin, which requires the proteolytic removal of the last 6 or 7 amino acids, in order to generate a high affinity ligand of chemR23. Two neutrophil proteases, elastase and cathepsin G, are able to mediate this conversion. Besides, a peptide derived from the intracellular protein heme-binding protein (HBP) has been characterized as the first specific ligand of the FPRL2 receptor. The role of these two new systems in the control of physiological and pathological inflammatory reactions is presently being studied.