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Updated: Mar 26, 2026

Real-time Imaging of Endothelial Cell-cell Junctions During Neutrophil Transmigration Under Physiological Flow
Published on: August 14, 2014
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.
Abstract:
ICAM-1 is required for firm adhesion of leukocytes to the endothelium. However, how the spatial organization of endothelial ICAM-1 regulates leukocyte adhesion is not well understood. In this study, we identified the calcium-effector protein annexin A2 as a novel binding partner for ICAM-1. ICAM-1 clustering promotes the ICAM-1-annexin A2 interaction and induces translocation of ICAM-1 into caveolin-1-rich membrane domains. Depletion of endothelial annexin A2 using RNA interference enhances ICAM-1 membrane mobility and prevents the translocation of ICAM-1 into caveolin-1-rich membrane domains. Surprisingly, this results in increased neutrophil adhesion and transendothelial migration under flow conditions and reduced crawling time, velocity, and lateral migration distance of neutrophils on the endothelium. In conclusion, our data show that annexin A2 limits neutrophil transendothelial migration by organizing the spatial distribution of ICAM-1.
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