A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR

Mol Cell. 2000 May;5(5):831-40. doi: 10.1016/s1097-2765(00)80323-8.


The glucocorticoid-regulated protein annexin I (lipocortin I) has been shown to mediate antiinflammatory activities of glucocorticoids, but the molecular basis of its action has remained elusive. Here we show that annexin I acts through the formyl peptide receptor (FPR) on human neutrophils. Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. Lower peptide concentrations possibly found in inflammatory situations elicit Ca2+ transients without fully activating the MAP kinase pathway. This causes a specific inhibition of the transendothelial migration of neutrophils and a desensitization of neutrophils toward a chemoattractant challenge. These findings identify annexin I peptides as novel, endogenous FPR ligands and establish a mechanistic basis of annexin I-mediated antiinflammatory effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Annexin A1 / pharmacology*
  • Calcium Signaling
  • Chemotaxis, Leukocyte / drug effects*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Drug Interactions
  • Endothelium, Vascular / physiology*
  • Humans
  • Molecular Sequence Data
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / physiology*
  • Peptide Fragments / pharmacology
  • Protein Binding
  • Receptors, Formyl Peptide
  • Receptors, Immunologic / metabolism*
  • Receptors, Peptide / metabolism*
  • Superoxides / metabolism


  • Annexin A1
  • Peptide Fragments
  • Receptors, Formyl Peptide
  • Receptors, Immunologic
  • Receptors, Peptide
  • Superoxides
  • N-Formylmethionine Leucyl-Phenylalanine