Activation of the chemotactic peptide receptor FPRL1 in monocytes phosphorylates the chemokine receptor CCR5 and attenuates cell responses to selected chemokines

FPRL1 is a seven-transmembrane (STM), G-protein coupled receptor which was originally identified as a low affinity receptor for the bacterial chemotac tic formyl peptide and a high affinity receptor for the Lipid metabolite li poxin A4. me recently discovered that a number of peptides, including sever al synthetic domains of the HIV-1 envelope proteins and the serum amyloid A , use FPRL1 to induce migration and calcium mobilization in human monocytes and neutrophils. In this study, we report that a synthetic peptide domain of the V3 region of the HIV-1 envelope gp120, activates the FPRL1 receptor in monocytes and neutrophils. Furthermore, monocytes prestimulated with V3 peptide showed reduced response to several chemokines that use multiple cel l receptors. This is associated with a rapid phosphorylation of the chemoki ne receptor CCR5 on the serine residues. Our study suggests that FPRL1, as a classical chemoattractant receptor, may play an important role in modulat ing monocyte activation in the presence of multiple stimuli. (C) 2000 Acade mic Press.