The neurotoxic prion peptide fragment PrP(106-126) is a chemotactic agonist for the G protein-coupled receptor formyl peptide receptor-like 1

J Immunol. 2001 Feb 1;166(3):1448-51. doi: 10.4049/jimmunol.166.3.1448.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Signaling / immunology
  • Cell Line
  • Chemotactic Factors / physiology*
  • Chemotactic Factors / toxicity
  • Chemotaxis, Leukocyte / immunology*
  • Cytokines / biosynthesis
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Ligands
  • Microglia / immunology
  • Microglia / metabolism
  • Monocytes / immunology
  • Monocytes / metabolism
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism*
  • Peptide Fragments / agonists*
  • Peptide Fragments / physiology
  • Peptide Fragments / toxicity*
  • Prions / agonists*
  • Prions / physiology
  • Prions / toxicity*
  • Rats
  • Receptors, Formyl Peptide
  • Receptors, Immunologic / metabolism
  • Receptors, Immunologic / physiology*
  • Receptors, Lipoxin*
  • Receptors, Peptide / metabolism
  • Receptors, Peptide / physiology*
  • Tumor Cells, Cultured

Substances

  • Chemotactic Factors
  • Cytokines
  • FPR2 protein, human
  • Ligands
  • Peptide Fragments
  • Prions
  • Receptors, Formyl Peptide
  • Receptors, Immunologic
  • Receptors, Lipoxin
  • Receptors, Peptide
  • prion protein (106-126)
  • N-Formylmethionine Leucyl-Phenylalanine
  • GTP-Binding Proteins