Journal
CLINICAL IMMUNOLOGY
Volume 99, Issue 3, Pages 365-372Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/clim.2001.5021
Keywords
chemokine receptor; receptor desensitization; N-formyl peptide; N-formyl peptide receptors; HIV-1
Categories
Funding
- NCI NIH HHS [N01-CO-56000] Funding Source: Medline
- NIDA NIH HHS [DA12113, DA11130, DA06650, T32DA07237, F31DA05894] Funding Source: Medline
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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. (C) 2001 Academic Press.
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