Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration

eLife

Teng Leong Chew¹  Satya Khuon¹  Eric Wait¹  John M Heddleston²  Barbara Walzog³  Eloi Montanez⁴  Ivar Noordstra⁵  Emma Gordon⁵  Marten Postma⁶  Eike K Mahlandt⁶  Joachim Goedhart⁶  Simon Tol⁷  Jos van Rijssel⁷  Abraham CI van Steen⁷  Martijn A Nolte⁷  Max LB Grönloh⁸  Jaap D van Buul⁸  Janine JG Arts⁸  Lilian Schimmel⁹  Mark Winter^1,10 

[1] Advanced Imaging Center at Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States;Advanced Imaging Center at Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States;Microscopy Facility at the Cleveland Clinic Florida Research and Innovation Center, Port St. Lucie, United States;Department of Cardiovascular Physiology and Pathophysiology, Walter Brendel Center of Experimental Medicine, Biomedical Center, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany;Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain;Division of Cell and Developmental Biology, Institute for Molecular Bioscience, The University of Queensland, BrisbaneQLD, Australia;Leeuwenhoek Centre for Advanced Microscopy (LCAM), section Molecular Cytology at Swammerdam Institute for Life Sciences (SILS) at University of Amsterdam, Amsterdam, Netherlands;Molecular Cell Biology Lab at Dept. Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands;Molecular Cell Biology Lab at Dept. Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands;Leeuwenhoek Centre for Advanced Microscopy (LCAM), section Molecular Cytology at Swammerdam Institute for Life Sciences (SILS) at University of Amsterdam, Amsterdam, Netherlands;Molecular Cell Biology Lab at Dept. Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands;Leeuwenhoek Centre for Advanced Microscopy (LCAM), section Molecular Cytology at Swammerdam Institute for Life Sciences (SILS) at University of Amsterdam, Amsterdam, Netherlands;Division of Cell and Developmental Biology, Institute for Molecular Bioscience, The University of Queensland, BrisbaneQLD, Australia;Zuckerman Postdoctoral Fellow, Department of Marine Sciences, University of Haifa, Haifa, Israel;

关键词: endothelium;    Transmigration;    protrusions;    GTPase;    actin;    inflammation;    Human;    Mouse;   

DOI  :  10.7554/eLife.66074

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Upon inflammation, leukocytes rapidly transmigrate across the endothelium to enter the inflamed tissue. Evidence accumulates that leukocytes use preferred exit sites, alhough it is not yet clear how these hotspots in the endothelium are defined and how they are recognized by the leukocyte. Using lattice light sheet microscopy, we discovered that leukocytes prefer endothelial membrane protrusions at cell junctions for transmigration. Phenotypically, these junctional membrane protrusions are present in an asymmetric manner, meaning that one endothelial cell shows the protrusion and the adjacent one does not. Consequently, leukocytes cross the junction by migrating underneath the protruding endothelial cell. These protrusions depend on Rac1 activity and by using a photo-activatable Rac1 probe, we could artificially generate local exit-sites for leukocytes. Overall, we have discovered a new mechanism that uses local induced junctional membrane protrusions to facilitate/steer the leukocyte escape/exit from inflamed vessel walls.

【 授权许可】

CC BY