Cutting edge: The neurotoxic prion peptide fragment PrP106-126 is a chemotactic agonist for the G protein-coupled receptor formyl peptide receptor-like 1
Yy. Le et al., Cutting edge: The neurotoxic prion peptide fragment PrP106-126 is a chemotactic agonist for the G protein-coupled receptor formyl peptide receptor-like 1, J IMMUNOL, 166(3), 2001, pp. 1448-1451
Prion diseases are transmissible and fatal neurodegenerative disorders whic
h involve infiltration and activation of mononuclear phagocytes at the brai
n lesions. A 20-aa acid fragment of the human cellular prion protein, PrP10
6-126, was reported to mimic the biological activity of the pathologic isof
orm of prion and activates mononuclear phagocytes, The cell surface recepto
r(s) mediating the activity of PrP106-126 is unknown. In this study, we sho
w that PrP106-126 is chemotactic for human monocytes through the use of a G
protein-coupled receptor formyl peptide receptor-like 1 (FPRL1), which has
been reported to interact with a diverse array of exogenous or endogenous
ligands. Upon stimulation by PrP106-126, FPRL1 underwent a rapid internaliz
ation and, furthermore, PrP106-126 enhanced monocyte production of proinfla
mmatory cytokines, which was inhibited by pertussis toxin, Thus, FPRL1 may
act as a "pattern recognition" receptor that interacts with multiple pathol
ogic agents and may be involved in the proinflammatory process of prion dis
eases.