Activation of the chemotactic peptide receptor FPRL1 in monocytes phosphorylates the chemokine receptor CCR5 and attenuates cell responses to selected chemokines.
FPRL1 is a seven-transmembrane (STM), G-protein coupled receptor which was originally identified as a low affinity receptor for the bacterial chemotactic formyl peptide and a high affinity receptor for the lipid metabolite lipoxin A4. We recently discovered that a number of peptides, including several synthetic domains of the HIV-1 envelope proteins and the serum amyloid A, use FPRL1 to induce migration and calcium mobilization in human monocytes and neutrophils. In this study, we report that a synthetic peptide domain of the V3 region of the HIV-1 envelope gp120, activates the FPRL1 receptor in monocytes and neutrophils. Furthermore, monocytes prestimulated with V3 peptide showed reduced response to several chemokines that use multiple cell receptors. This is associated with a rapid phosphorylation of the chemokine receptor CCR5 on the serine residues. Our study suggests that FPRL1, as a classical chemoattractant receptor, may play an important role in modulating monocyte activation in the presence of multiple stimuli.
Shen
W
W
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research & Development Center, Maryland 21702-1201, USA.
Proost
P
P
Li
B
B
Gong
W
W
Le
Y
Y
Sargeant
R
R
Murphy
P M
PM
Van Damme
J
J
Wang
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D020013:Calcium Signaling; D002460:Cell Line; D018925:Chemokines / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation; D051381:Rats; D019713:Receptors, CCR5 / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*
D018925:Chemokines; C105101:FPR2 protein, human; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide