NR AHCO
AU Le,Y.; Yazawa,H.; Gong,W.; Yu,Z.; Ferrans,V.J.; Murphy,P.M.; Wang,J.M.
TI The neurotoxic prion peptide fragment PrP(106-126) is a chemotactic agonist for the G protein-coupled receptor formyl peptide receptor-like 1
QU Journal of Immunology 2001 Feb 1; 166(3): 1448-51
PT journal article
AB 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, PrP(106-126), 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 PrP(106-126) is unknown. In this study, we show that PrP(106-126) 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 PrP(106-126), FPRL1 underwent a rapid internalization and, furthermore, PrP(106-126) 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.
MH Animal; Calcium Signaling/immunology; Cell Line; Chemotactic Factors/*physiology/toxicity; Chemotaxis, Leukocyte/*immunology; Cytokines/biosynthesis; GTP-Binding Proteins/*metabolism; Human; Inflammation/immunology/metabolism; Ligands; Microglia/immunology/metabolism; Monocytes/immunology/metabolism; N-Formylmethionine Leucyl-Phenylalanine/*metabolism; Peptide Fragments/*agonists/physiology/*toxicity; Prions/*agonists/physiology/*toxicity; Rats; Receptors, Immunologic/metabolism/*physiology; Receptors, Peptide/metabolism/*physiology; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured
AD Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute-Frederick, Science Applications International Corporation-Frederick, Frederick, MD 21702, USA
SP englisch
PO USA