title: Desensitization of chemokine receptor CCR5 in dendritic cells at the early stage of differentiation by activation of formyl peptide receptors.
abstract: Chemokine receptors are subjected to heterologous desensitization by activation of formyl peptide receptors. We investigated the cross-talk between formyl peptide receptors and the chemokine receptor CCR5 in human monocyte-differentiated immature dendritic cells (iDC). Monocytes cultured with GM-CSF and IL-4 for 4 days exhibit markers characteristic of iDC and maintain the expression of both formyl peptide receptors FPR and FPRL1, as well as CCR5. Pretreatment of iDC with W peptide (WKYMVm), a potent agonist for FPR and FPRL1 but with preference for FPRL1, resulted in down-regulation of CCR5 from the cell surface and reduced cell response to the CCR5 ligands through a PKC-dependent pathway. Furthermore, W peptide induced a PKC-dependent phosphorylation of CCR5 and inhibited infection of iDC by R5 HIV-1. Our results indicate that the expression and functions of CCR5 in iDC can be attenuated by W peptide, which activates formyl peptide receptors, and suggest an approach to the design of novel anti-HIV-1 agents.
authors.affiliation: Laboratory of Molecular Immunoregulation, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Le
authors.forename: M A
authors.initials: MA
authors.lastname: Wetzel
authors.forename: W
authors.initials: W
authors.lastname: Shen
authors.forename: W
authors.initials: W
authors.lastname: Gong
authors.forename: T J
authors.initials: TJ
authors.lastname: Rogers
authors.forename: E E
authors.initials: EE
authors.lastname: Henderson
authors.forename: J M
authors.initials: JM
authors.lastname: Wang
mesh_terms: D002454:Cell Differentiation; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D003713:Dendritic Cells / Q000502:physiology* / Q000821:virology; D015536:Down-Regulation; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D010766:Phosphorylation; D019713:Receptors, CCR5 / Q000502:physiology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology*; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000502:physiology*
chemical_list: D054407:Chemokine CCL4; D018946:Chemokine CCL5; C105101:FPR2 protein, human; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide