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Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM‐1

Upon inflammation, leukocytes leave the circulation by crossing the endothelial monolayer at specific transmigration “hotspot” regions. Although these regions support leukocyte transmigration, their functionality is not clear. We found that endothelial hotspots function to limit vascular leakage dur...

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Autores principales: Grönloh, Max L B, Arts, Janine J G, Palacios Martínez, Sebastián, van der Veen, Amerens A, Kempers, Lanette, van Steen, Abraham C I, Roelofs, Joris J T H, Nolte, Martijn A, Goedhart, Joachim, van Buul, Jaap D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827561/
https://www.ncbi.nlm.nih.gov/pubmed/36382783
http://dx.doi.org/10.15252/embr.202255483
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author Grönloh, Max L B
Arts, Janine J G
Palacios Martínez, Sebastián
van der Veen, Amerens A
Kempers, Lanette
van Steen, Abraham C I
Roelofs, Joris J T H
Nolte, Martijn A
Goedhart, Joachim
van Buul, Jaap D
author_facet Grönloh, Max L B
Arts, Janine J G
Palacios Martínez, Sebastián
van der Veen, Amerens A
Kempers, Lanette
van Steen, Abraham C I
Roelofs, Joris J T H
Nolte, Martijn A
Goedhart, Joachim
van Buul, Jaap D
author_sort Grönloh, Max L B
collection PubMed
description Upon inflammation, leukocytes leave the circulation by crossing the endothelial monolayer at specific transmigration “hotspot” regions. Although these regions support leukocyte transmigration, their functionality is not clear. We found that endothelial hotspots function to limit vascular leakage during transmigration events. Using the photoconvertible probe mEos4b, we traced back and identified original endothelial transmigration hotspots. Using this method, we show that the heterogeneous distribution of ICAM‐1 determines the location of the transmigration hotspot. Interestingly, the loss of ICAM‐1 heterogeneity either by CRISPR/Cas9‐induced knockout of ICAM‐1 or equalizing the distribution of ICAM‐1 in all endothelial cells results in the loss of TEM hotspots but not necessarily in reduced TEM events. Functionally, the loss of endothelial hotspots results in increased vascular leakage during TEM. Mechanistically, we demonstrate that the 3 extracellular Ig‐like domains of ICAM‐1 are crucial for hotspot recognition. However, the intracellular tail of ICAM‐1 and the 4(th) Ig‐like dimerization domain are not involved, indicating that intracellular signaling or ICAM‐1 dimerization is not required for hotspot recognition. Together, we discovered that hotspots function to limit vascular leakage during inflammation‐induced extravasation.
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spelling pubmed-98275612023-01-11 Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM‐1 Grönloh, Max L B Arts, Janine J G Palacios Martínez, Sebastián van der Veen, Amerens A Kempers, Lanette van Steen, Abraham C I Roelofs, Joris J T H Nolte, Martijn A Goedhart, Joachim van Buul, Jaap D EMBO Rep Articles Upon inflammation, leukocytes leave the circulation by crossing the endothelial monolayer at specific transmigration “hotspot” regions. Although these regions support leukocyte transmigration, their functionality is not clear. We found that endothelial hotspots function to limit vascular leakage during transmigration events. Using the photoconvertible probe mEos4b, we traced back and identified original endothelial transmigration hotspots. Using this method, we show that the heterogeneous distribution of ICAM‐1 determines the location of the transmigration hotspot. Interestingly, the loss of ICAM‐1 heterogeneity either by CRISPR/Cas9‐induced knockout of ICAM‐1 or equalizing the distribution of ICAM‐1 in all endothelial cells results in the loss of TEM hotspots but not necessarily in reduced TEM events. Functionally, the loss of endothelial hotspots results in increased vascular leakage during TEM. Mechanistically, we demonstrate that the 3 extracellular Ig‐like domains of ICAM‐1 are crucial for hotspot recognition. However, the intracellular tail of ICAM‐1 and the 4(th) Ig‐like dimerization domain are not involved, indicating that intracellular signaling or ICAM‐1 dimerization is not required for hotspot recognition. Together, we discovered that hotspots function to limit vascular leakage during inflammation‐induced extravasation. John Wiley and Sons Inc. 2022-11-16 /pmc/articles/PMC9827561/ /pubmed/36382783 http://dx.doi.org/10.15252/embr.202255483 Text en © 2022 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Grönloh, Max L B
Arts, Janine J G
Palacios Martínez, Sebastián
van der Veen, Amerens A
Kempers, Lanette
van Steen, Abraham C I
Roelofs, Joris J T H
Nolte, Martijn A
Goedhart, Joachim
van Buul, Jaap D
Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM‐1
title Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM‐1
title_full Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM‐1
title_fullStr Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM‐1
title_full_unstemmed Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM‐1
title_short Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM‐1
title_sort endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of icam‐1
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827561/
https://www.ncbi.nlm.nih.gov/pubmed/36382783
http://dx.doi.org/10.15252/embr.202255483
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