F2L, a Peptide Derived from Heme-Binding Protein, Chemoattracts Mouse Neutrophils by Specifically Activating Fpr2, the Low-Affinity N-Formylpeptide Receptor

摘要: F2L (formylpeptide receptor (FPR)-like (FPRL)-2 ligand), a highly conserved acetylated peptide derived from the amino-terminal cleavage of heme-binding protein, is potent chemoattractant for human monocytes and dendritic cells, inhibits LPS-induced cell maturation. We recently reported that able to activate receptors FPRL-1 FPRL2, two members FPR family, with highest selectivity affinity FPRL2. To facilitate delineation mechanisms action in vivo, we have now attempted define its mouse receptors. This complicated by nonequivalence gene families (three vs at least eight members, respectively). When lines were transfected plasmids encoding receptors, only one expressing Fpr2 responded (EC(50) approximately 400 nM both calcium flux cAMP inhibition assays). value similar potency FPRL1. Consistent this, neutrophils, which like macrophages cells express Fpr2, chemotaxis assays EC(50) values those found Fpr2-expressing ( 500 nM). Moreover, neutrophils mice genetically deficient failed respond F2L. Thus, F2L, can be targeted study models.