Desensitization of Chemokine Receptor CCR5 in Dendritic Cells at the Early Stage of Differentiation by Activation of Formyl Peptide Receptors

Autor: Wanghua Gong, Earl E. Henderson, Thomas J. Rogers, Michele A. Wetzel, Weiping Shen, Ji Ming Wang, Yingying Le
Rok vydání: 2001
Předmět:
Zdroj: Clinical Immunology. 99:365-372
ISSN: 1521-6616
Popis: 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.
Databáze: OpenAIRE