Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration
- Sanquin Research and Landsteiner Laboratory, Netherlands
- SILS/UvA, Netherlands
- Uppsala University, Sweden
- Ludwig-Maximilians-Universität München, Germany
- Janelia Research Campus, United States
- Howard Hughes Medical Institute, United States
- University of Haifa, Israel
- University of Barcelona, Spain
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
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
- Carla V Rothlin, Yale School of Medicine, United States
Publication history
- Received: December 24, 2020
- Preprint posted: January 21, 2021 (view preprint)
- Accepted: August 22, 2021
- Accepted Manuscript published: August 25, 2021 (version 1)
- 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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