T21/DP107, a synthetic leucine zipper-like domain of the HIV-1 envelope gp41, attracts and activates human phagocytes by using G-protein-coupled formyl peptide receptors
Sb. Su et al., T21/DP107, a synthetic leucine zipper-like domain of the HIV-1 envelope gp41, attracts and activates human phagocytes by using G-protein-coupled formyl peptide receptors, J IMMUNOL, 162(10), 1999, pp. 5924-5930
A leucine zipper-like domain, T21/DP107, located in the amino terminus of t
he ectodomain of gp41, is crucial to the formation of fusogenic configurati
on of the HIV-1 envelope protein gp41. We report that the synthetic T21/DP1
07 segment is a potent stimulant of migration and calcium mobilization in h
uman monocytes and neutrophils, The activity of T21/DP107 on phagocytes was
pertussis toxin-sensitive, suggesting this peptide uses Gi-coupled seven-t
ransmembrane receptor(s), Since the bacterial chemotactic peptide fMLP part
ially desensitized the calcium-mobilizing activity of T21/DP107 in phagocyt
es, we postulated that T21/DP107 might preferentially use a lower affinity
fMLP receptor. By using cells transfected to express cloned prototype chemo
tactic N-formyl peptide receptor (FPR) or its variant, FPR-like 1 (FPRL1),
we demonstrate that T21/DP107 activates both receptors but has a much highe
r efficacy for FPRL1, In addition, T21/DP107 at nM concentrations induced m
igration of FPRL1-transfected human embryonic kidney 293 cells. In contrast
, fMLP did not induce significant chemotaxis of the same cells at a concent
ration as high as 50 mu M Although a lipid metabolite, lipoxin A4, was a hi
gh-affinity ligand for FPRL1, it was not reported to induce Ca2+ mobilizati
on or chemotaxis in FPRL1-transfected cells. Therefore, T21/DP107 is a firs
t chemotactic peptide agonist identified thus far for FPRL1. Our results su
ggest that this peptide domain of the HIV-1 gp41 may have the potential to
activate host innate immune response by interacting with FPR and FPRL1 on p
hagocytes.