title: Annexin A2 Limits Neutrophil Transendothelial Migration by Organizing the Spatial Distribution of ICAM-1.
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.
authors: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.
authors: Niels
authors: http://orcid.org/0000-0003-2340-537X
authors: N
authors: Heemskerk
authors: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.
authors: Mohammed
authors: M
authors: Asimuddin
authors: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.
authors: Chantal
authors: C
authors: Oort
authors: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.
authors: Jos
authors: http://orcid.org/0000-0001-8077-1371
authors: J
authors: van Rijssel
authors: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands j.vanbuul@sanquin.nl.
authors: Jaap D
authors: http://orcid.org/0000-0003-0054-7949
authors: JD
authors: van Buul
mesh_terms: D017306:Annexin A2 / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D042783:Endothelial Cells / Q000276:immunology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011485:Protein Binding; D021381:Protein Transport; D011940:Receptor Aggregation; D057705:Transendothelial and Transepithelial Migration
chemical_list: D017306:Annexin A2; D051242:Caveolin 1; D018799:Intercellular Adhesion Molecule-1