Annexin A2 Limits Neutrophil Transendothelial Migration by Organizing the Spatial Distribution of ICAM-1

Niels Heemskerk1, Mohammed Asimuddin1, Chantal Oort1

  • 1Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.

Insights

Annexin A2 limits neutrophil migration by organizing ICAM-1 distribution. Depleting annexin A2 increases neutrophil adhesion and transendothelial migration, revealing its role in regulating leukocyte-endothelial interactions.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Intercellular Adhesion Molecule 1 (ICAM-1) is crucial for leukocyte firm adhesion to endothelium.
  • The precise spatial regulation of endothelial ICAM-1 in leukocyte adhesion remains unclear.

Purpose of the Study:

  • To investigate the novel binding partner of ICAM-1 and its role in leukocyte adhesion.
  • To elucidate how annexin A2 influences the spatial organization and function of ICAM-1.

Main Methods:

  • Identified annexin A2 as a novel ICAM-1 binding partner.
  • Utilized RNA interference to deplete endothelial annexin A2.
  • Observed ICAM-1 clustering, membrane domain translocation, and neutrophil behavior under flow conditions.

Main Results:

  • Annexin A2 binds to ICAM-1, promoting its clustering and translocation into caveolin-1-rich domains.
  • Annexin A2 depletion increases ICAM-1 mobility and prevents its domain translocation.
  • Loss of annexin A2 leads to enhanced neutrophil adhesion and transendothelial migration, with reduced neutrophil crawling.

Conclusions:

  • Annexin A2 is a key regulator of ICAM-1 spatial organization.
  • Annexin A2 limits neutrophil transendothelial migration by controlling ICAM-1 distribution.
  • This study reveals a novel mechanism for regulating leukocyte-endothelial interactions.

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