Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes

Interactions between cell surface receptors are important regulatory elemen ts in the complex host responses to infections. In this study, it is shown that a classic chemotactic factor, the bacterial chemotactic peptide N-form yl-methionyl-leucylphenyl-alanine (fMLF), rapidly induced a protein-kinase- C-mediated serine phosphorylation and down-regulation of the chemokine rece ptor CCR5, which serves as a major human immunodeficiency virus (HIV)-1 cor eceptor. The fMLF binding to its receptor, formyl peptide receptor (FPR), r esulted in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1-envelope-glycoprotein-mediated fusion and infection of cells expressing CD4, CCR5, and FPR, The finding that the expression and f unction of CCR5 can be regulated by peptides that use an unrelated receptor may provide a novel approach to the design of anti-inflamatory and antiret roviral agents. (Blood, 2000;96:2887-2894) (C) 2000 by The American Society of Hematology.