1. Cell Biology
  2. Immunology and Inflammation
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Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration

  1. Janine JG Arts
  2. Eike K Mahlandt
  3. Max Grönloh
  4. Lilian Schimmel
  5. Ivar Noordstra
  6. Emma Gordon
  7. Abraham CI van Steen
  8. Simon Tol
  9. Barbara Walzog
  10. Jos van Rijssel
  11. Martijn A Nolte
  12. Marten Postma
  13. Satya Khuon
  14. John M Heddleston
  15. Eric Wait
  16. Teng Leong Chew
  17. Mark Winter
  18. Eloi Montanez
  19. Joachim Goedhart
  20. Jaap D van Buul  Is a corresponding author
  1. Sanquin Research and Landsteiner Laboratory, Netherlands
  2. SILS/UvA, Netherlands
  3. Uppsala University, Sweden
  4. Ludwig-Maximilians-Universität München, Germany
  5. Janelia Research Campus, United States
  6. Howard Hughes Medical Institute, United States
  7. University of Haifa, Israel
  8. University of Barcelona, Spain
Research Article
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Cite this article as: eLife 2021;10:e66074 doi: 10.7554/eLife.66074

Abstract

Upon inflammation, leukocytes rapidly transmigrate across the endothelium to enter the inflamed tissue. Evidence accumulates that leukocytes use preferred exit sites, though 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.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files will be provided for Figures 4 and 6.

Article and author information

Author details

  1. Janine JG Arts

    Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Eike K Mahlandt

    Molecular Cytology, SILS/UvA, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Max Grönloh

    Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0109-8225
  4. Lilian Schimmel

    Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0569-0464
  5. Ivar Noordstra

    Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Emma Gordon

    Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Abraham CI van Steen

    Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. Simon Tol

    Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  9. Barbara Walzog

    Ludwig-Maximilians-Universität München, Planegg- Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Jos van Rijssel

    Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8077-1371
  11. Martijn A Nolte

    Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  12. Marten Postma

    Molecular Cytology, SILS/UvA, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  13. Satya Khuon

    Advanced Imaging Center, Janelia Research Campus, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. John M Heddleston

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Eric Wait

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Teng Leong Chew

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Mark Winter

    Department of Marine Sciences, University of Haifa, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1180-1957
  18. Eloi Montanez

    Department of Physiological Sciences, University of Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4059-5056
  19. Joachim Goedhart

    Molecular Cytology, SILS/UvA, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0630-3825
  20. Jaap D van Buul

    Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
    For correspondence
    j.vanbuul@sanquin.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0054-7949

Funding

LSBR (1649)

  • Abraham CI van Steen

NWO-ZonMW Vici (91819632)

  • Max Grönloh
  • Jaap D van Buul

Spanish Ministry of Science, Innovation and Universities (PID2019-108902GB-I00)

  • Eloi Montanez

NWO ALW-OPEN (ALWOP.306)

  • Eike K Mahlandt

Deutsche Forschungsgemeinschaft (SFB 914/A02)

  • Barbara Walzog

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were conducted in accordance with German federal animal protection laws and were approved by the Bavarian Government (Regierung von Oberbayern, Munich, Germany)

Reviewing Editor

  1. Carla V Rothlin, Yale School of Medicine, United States

Publication history

  1. Received: December 24, 2020
  2. Preprint posted: January 21, 2021 (view preprint)
  3. Accepted: August 22, 2021
  4. Accepted Manuscript published: August 25, 2021 (version 1)
  5. Version of Record published: September 13, 2021 (version 2)

Copyright

© 2021, Arts et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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