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ADAM10-Mediated Cleavage of ICAM-1 Is Involved in Neutrophil Transendothelial Migration

To efficiently cross the endothelial barrier during inflammation, neutrophils first firmly adhere to the endothelial surface using the endothelial adhesion molecule ICAM-1. Upon actual transmigration, the release from ICAM-1 is required. While Integrin LFA1/Mac1 de-activation is one described mechan...

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Autores principales: Morsing, Sofia K. H., Rademakers, Timo, Brouns, Sanne L. N., van Stalborch, Anne-Marieke D., Donners, Marjo M. P. C., van Buul, Jaap D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911467/
https://www.ncbi.nlm.nih.gov/pubmed/33504031
http://dx.doi.org/10.3390/cells10020232
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author Morsing, Sofia K. H.
Rademakers, Timo
Brouns, Sanne L. N.
van Stalborch, Anne-Marieke D.
Donners, Marjo M. P. C.
van Buul, Jaap D.
author_facet Morsing, Sofia K. H.
Rademakers, Timo
Brouns, Sanne L. N.
van Stalborch, Anne-Marieke D.
Donners, Marjo M. P. C.
van Buul, Jaap D.
author_sort Morsing, Sofia K. H.
collection PubMed
description To efficiently cross the endothelial barrier during inflammation, neutrophils first firmly adhere to the endothelial surface using the endothelial adhesion molecule ICAM-1. Upon actual transmigration, the release from ICAM-1 is required. While Integrin LFA1/Mac1 de-activation is one described mechanism that leads to this, direct cleavage of ICAM-1 from the endothelium represents a second option. We found that a disintegrin and metalloprotease 10 (ADAM10) cleaves the extracellular domain of ICAM-1 from the endothelial surface. Silencing or inhibiting endothelial ADAM10 impaired the efficiency of neutrophils to cross the endothelium, suggesting that neutrophils use endothelial ADAM10 to dissociate from ICAM-1. Indeed, when measuring transmigration kinetics, neutrophils took almost twice as much time to finish the diapedesis step when ADAM10 was silenced. Importantly, we found increased levels of ICAM-1 on the transmigrating neutrophils when crossing an endothelial monolayer where such increased levels were not detected when neutrophils crossed bare filters. Using ICAM-1-GFP-expressing endothelial cells, we show that ICAM-1 presence on the neutrophils can also occur by membrane transfer from the endothelium to the neutrophil. Based on these findings, we conclude that endothelial ADAM10 contributes in part to neutrophil transendothelial migration by cleaving ICAM-1, thereby supporting the release of neutrophils from the endothelium during the final diapedesis step.
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spelling pubmed-79114672021-02-28 ADAM10-Mediated Cleavage of ICAM-1 Is Involved in Neutrophil Transendothelial Migration Morsing, Sofia K. H. Rademakers, Timo Brouns, Sanne L. N. van Stalborch, Anne-Marieke D. Donners, Marjo M. P. C. van Buul, Jaap D. Cells Article To efficiently cross the endothelial barrier during inflammation, neutrophils first firmly adhere to the endothelial surface using the endothelial adhesion molecule ICAM-1. Upon actual transmigration, the release from ICAM-1 is required. While Integrin LFA1/Mac1 de-activation is one described mechanism that leads to this, direct cleavage of ICAM-1 from the endothelium represents a second option. We found that a disintegrin and metalloprotease 10 (ADAM10) cleaves the extracellular domain of ICAM-1 from the endothelial surface. Silencing or inhibiting endothelial ADAM10 impaired the efficiency of neutrophils to cross the endothelium, suggesting that neutrophils use endothelial ADAM10 to dissociate from ICAM-1. Indeed, when measuring transmigration kinetics, neutrophils took almost twice as much time to finish the diapedesis step when ADAM10 was silenced. Importantly, we found increased levels of ICAM-1 on the transmigrating neutrophils when crossing an endothelial monolayer where such increased levels were not detected when neutrophils crossed bare filters. Using ICAM-1-GFP-expressing endothelial cells, we show that ICAM-1 presence on the neutrophils can also occur by membrane transfer from the endothelium to the neutrophil. Based on these findings, we conclude that endothelial ADAM10 contributes in part to neutrophil transendothelial migration by cleaving ICAM-1, thereby supporting the release of neutrophils from the endothelium during the final diapedesis step. MDPI 2021-01-25 /pmc/articles/PMC7911467/ /pubmed/33504031 http://dx.doi.org/10.3390/cells10020232 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Morsing, Sofia K. H.
Rademakers, Timo
Brouns, Sanne L. N.
van Stalborch, Anne-Marieke D.
Donners, Marjo M. P. C.
van Buul, Jaap D.
ADAM10-Mediated Cleavage of ICAM-1 Is Involved in Neutrophil Transendothelial Migration
title ADAM10-Mediated Cleavage of ICAM-1 Is Involved in Neutrophil Transendothelial Migration
title_full ADAM10-Mediated Cleavage of ICAM-1 Is Involved in Neutrophil Transendothelial Migration
title_fullStr ADAM10-Mediated Cleavage of ICAM-1 Is Involved in Neutrophil Transendothelial Migration
title_full_unstemmed ADAM10-Mediated Cleavage of ICAM-1 Is Involved in Neutrophil Transendothelial Migration
title_short ADAM10-Mediated Cleavage of ICAM-1 Is Involved in Neutrophil Transendothelial Migration
title_sort adam10-mediated cleavage of icam-1 is involved in neutrophil transendothelial migration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911467/
https://www.ncbi.nlm.nih.gov/pubmed/33504031
http://dx.doi.org/10.3390/cells10020232
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