Utilization of two seven-transmembrane, G protein-coupled receptors, formyl peptide receptor-like 1 and formyl peptide receptor, by the synthetic hexapeptide WKYMVm for human phagocyte activation
Yy. Le et al., Utilization of two seven-transmembrane, G protein-coupled receptors, formyl peptide receptor-like 1 and formyl peptide receptor, by the synthetic hexapeptide WKYMVm for human phagocyte activation, J IMMUNOL, 163(12), 1999, pp. 6777-6784
Trp-Lys-Tyr-Val-D-Met (WKYMVm) is a synthetic leukocyte-activating peptide
postulated to use seven-transmembrane, G protein-coupled receptor(s), In th
e study to characterize the receptor(s) for WKYMVm, we found that this pept
ide induced marked chemotaxis and calcium flux in human phagocytes, The sig
naling induced by WKYMVm in phagocytes was attenuated by high concentration
s of the bacterial chemotactic peptide fMLP, suggesting that WKYMVm might u
se receptor(s) for fMLP. This hypothesis was tested by using cells over exp
ressing genes encoding two seven-transmembrane receptors, formyl peptide re
ceptor (FPR) and formyl peptide receptor-like 1 (FPRL1), which are with hig
h and low affinity for fMLP, respectively. Both FPR- and FPRL1-expressing c
ells mobilized calcium in response to picomolar concentrations of WKYMVm, W
hile FPRL1-expressing cells migrated to picomolar concentrations of WKYMVm,
nanomolar concentrations of the peptide were required to induce migration
of FPR-expressing cells. In contrast, fMLP elicited both calcium flux and c
hemotaxis only in FPR-expressing cells with an efficacy comparable with WKY
MVm, Thus, WKYMVm uses both FPR and FPRL1 to stimulate phagocytes with a ma
rkedly higher efficacy for FPRL1, Our study suggests that FPR and FPRL1 in
phagocytes react to a broad spectrum of agonists and WKYMVm as a remarkably
potent agonist provides a valuable tool for studying leukocyte signaling v
ia these receptors.