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 elements in the complex host responses to infections. In this study, it is shown that a classic chemotactic factor, the bacterial chemotactic peptide N-formyl-methionyl-leucylphenyl-alanine (fMLF), rapidly induced a protein-kinase-C-mediated serine phosphorylation and down-regulation of the chemokine receptor CCR5, which serves as a major human immunodeficiency virus (HIV)-1 coreceptor. The fMLF binding to its receptor, formyl peptide receptor (FPR), resulted 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 function of CCR5 can be regulated by peptides that use an unrelated receptor may provide a novel approach to the design of anti-inflamatory and antiretroviral agents. (Blood. 2000;96:2887-2894)
Shen
W
W
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702-1201, USA.
Li
B
B
Wetzel
M A
MA
Rogers
T J
TJ
Henderson
E E
EE
Su
S B
SB
Gong
W
W
Le
Y
Y
Sargeant
R
R
Dimitrov
D S
DS
Oppenheim
J J
JJ
Wang
J M
JM
D019380:Anti-HIV Agents / Q000494:pharmacology; D002459:Cell Fusion; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D015536:Down-Regulation / Q000187:drug effects*; D015195:Drug Design; D015686:Gene Products, env / Q000502:physiology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000502:physiology; D018000:Receptors, Peptide / Q000187:drug effects* / Q000502:physiology; D014162:Transfection
D019380:Anti-HIV Agents; D015686:Gene Products, env; D019713:Receptors, CCR5; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C