Wp. Shen et al., Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes, BLOOD, 96(8), 2000, pp. 2887-2894
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-enveiopeglycoprotein-mediated fusion and infection of
cells expressing CD4, CCR5, and FPR, The finding that the expression and fu
nction of CCR5 can be regulated by peptides that use an unrelated receptor
may provide a novel approach to the design of anti-inflamatory and antiretr
oviral agents. (C) 2000 by The American Society of Hematology.