Endothelial Focal Adhesions Are Functional Obstacles for Leukocytes During Basolateral Crawling.
Autor: | Arts JJG; Molecular Cell Biology Lab, Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands.; Leeuwenhoek Centre for Advanced Microscopy (LCAM), Section of Molecular Cytology, Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, Amsterdam, Netherlands., Mahlandt EK; Leeuwenhoek Centre for Advanced Microscopy (LCAM), Section of Molecular Cytology, Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, Amsterdam, Netherlands., Schimmel L; Molecular Cell Biology Lab, Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands., Grönloh MLB; Molecular Cell Biology Lab, Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands., van der Niet S; Molecular Cell Biology Lab, Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands., Klein BJAM; Molecular Cell Biology Lab, Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands., Fernandez-Borja M; Molecular Cell Biology Lab, Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands., van Geemen D; Molecular Cell Biology Lab, Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands., Huveneers S; Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands., van Rijssel J; Molecular Cell Biology Lab, Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands., Goedhart J; Leeuwenhoek Centre for Advanced Microscopy (LCAM), Section of Molecular Cytology, Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, Amsterdam, Netherlands., van Buul JD; Molecular Cell Biology Lab, Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands.; Leeuwenhoek Centre for Advanced Microscopy (LCAM), Section of Molecular Cytology, Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, Amsterdam, Netherlands. |
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Jazyk: | angličtina |
Zdroj: | Frontiers in immunology [Front Immunol] 2021 May 18; Vol. 12, pp. 667213. Date of Electronic Publication: 2021 May 18 (Print Publication: 2021). |
DOI: | 10.3389/fimmu.2021.667213 |
Abstrakt: | An inflammatory response requires leukocytes to migrate from the circulation across the vascular lining into the tissue to clear the invading pathogen. Whereas a lot of attention is focused on how leukocytes make their way through the endothelial monolayer, it is less clear how leukocytes migrate underneath the endothelium before they enter the tissue. Upon finalization of the diapedesis step, leukocytes reside in the subendothelial space and encounter endothelial focal adhesions. Using TIRF microscopy, we show that neutrophils navigate around these focal adhesions. Neutrophils recognize focal adhesions as physical obstacles and deform to get around them. Increasing the number of focal adhesions by silencing the small GTPase RhoJ slows down basolateral crawling of neutrophils. However, apical crawling and diapedesis itself are not affected by RhoJ depletion. Increasing the number of focal adhesions drastically by expressing the Rac1 GEF Tiam1 make neutrophils to avoid migrating underneath these Tiam1-expressing endothelial cells. Together, our results show that focal adhesions mark the basolateral migration path of neutrophils. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Arts, Mahlandt, Schimmel, Grönloh, van der Niet, Klein, Fernandez-Borja, van Geemen, Huveneers, van Rijssel, Goedhart and van Buul.) |
Databáze: | MEDLINE |
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