Cutting edge:: The neurotoxic prion peptide fragment PrP106-126 is a chemotactic agonist for the G protein-coupled receptor formyl peptide receptor-like 1

Prion diseases are transmissible and fatal neurodegenerative disorders which involve infiltration and activation of mononuclear phagocytes at the brain lesions. A 20-aa acid fragment of the human cellular prion protein, PrP106-126, was reported to mimic the biological activity of the pathologic isoform of prion and activates mononuclear phagocytes, The cell surface receptor(s) mediating the activity of PrP106-126 is unknown. In this study, we show 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 internalization and, furthermore, PrP106-126 enhanced monocyte production of proinflammatory cytokines, which was inhibited by pertussis toxin, Thus, FPRL1 may act as a pattern recognition receptor that interacts with multiple pathologic agents and may be involved in the proinflammatory process of prion diseases.