Annexin 1 cleavage in activated neutrophils: a pivotal role for proteinase 3

Linda Vong, Fulvio D'Acquisto, Magali Pederzoli-Ribeil, Luisa Lavagno, Roderick J Flower, Véronique Witko-Sarsat, Mauro Perretti

Research output: Contribution to journalArticlepeer-review


Annexin 1 is an anti-inflammatory protein that plays a key role in innate immunity by modulating the activation of several types of cells, including neutrophils. Here we have developed a cleavage assay using tagged annexin 1 and observed marked activity in the membrane fraction of activated neutrophils. A combination of inhibitors, transfected cells, and proteomic analyses allowed us to identify proteinase 3 as the main enzyme responsible for this cleavage in the N terminus region of the protein, at least in the context of neutrophil activation. Because annexin 1 is an important endogenous anti-inflammatory mediator, blocking its cleavage by proteinase 3 would augment its homeostatic pro-resolving actions and could represent an opportunity for innovative anti-inflammatory drug discovery.

Original languageEnglish
Pages (from-to)29998-30004
Number of pages7
Issue number41
Publication statusPublished - 12 Oct 2007


  • Amino Acid Sequence
  • Annexin A1
  • Anti-Inflammatory Agents
  • Cell Line
  • Chemistry, Pharmaceutical
  • Drug Design
  • Epithelial Cells
  • Gene Expression Regulation, Enzymologic
  • HL-60 Cells
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Myeloblastin
  • Neutrophil Activation
  • Neutrophils
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Journal Article
  • Research Support, Non-U.S. Gov't

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