Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles

Jesmond Dalli1, Lucy V Norling, Derek Renshaw

  • 1The William Harvey Research Institute, Barts and The London Medical School, London, United Kingdom.

Blood
|July 3, 2008
PubMed

Insights

Polymorphonuclear leukocyte (PMN)-derived microparticles contain active annexin 1 (AnxA1), inhibiting inflammatory cell adhesion and recruitment. These microparticles offer a novel therapeutic strategy for resolving inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Polymorphonuclear leukocytes (PMNs) are key inflammatory cells.
  • PMN-derived microparticles may possess regulatory functions.
  • Annexin A1 (AnxA1) is an endogenous anti-inflammatory protein found in PMNs.

Purpose of the Study:

  • To investigate the presence and function of AnxA1 in PMN-derived microparticles.
  • To determine if AnxA1 in these microparticles confers anti-inflammatory properties.
  • To explore the therapeutic potential of PMN-derived microparticles in inflammation.

Main Methods:

  • Generation of microparticles from PMN adhesion to HUVECs.
  • Detection of AnxA1 in microparticles using Western blotting, flow cytometry, and mass spectrometry.
  • In vitro assays assessing microparticle inhibition of PMN adhesion.
  • In vivo studies using an air pouch inflammation model and AnxA1-null PMNs.

Main Results:

  • PMN-derived microparticles were found to contain AnxA1.
  • These microparticles significantly inhibited PMN adhesion to endothelial cells in vitro.
  • This inhibitory effect was dependent on AnxA1 and its receptor, ALX.
  • In vivo administration of microparticles reduced PMN recruitment to inflamed tissue.
  • The anti-inflammatory effect in vivo was dependent on the presence of AnxA1 in the microparticles.

Conclusions:

  • PMN-derived microparticles contain functionally active AnxA1.
  • These microparticles possess potent anti-inflammatory properties.
  • Microparticle generation in vivo could contribute to the resolution of inflammation by modulating leukocyte recruitment.

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