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Vitronectin stabilizes intravascular adhesion of neutrophils by coordinating b2 integrin clustering

The recruitment of neutrophils from the microvasculature to the site of injury or infection represents a key event in the inflammatory response. Vitronectin (VN) is a multifunctional macromolecule abundantly present in blood and extracellular matrix. The role of this glycoprotein in the extravasatio...

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Autores principales: Zuchtriegel, Gabriele, Uhl, Bernd, Pick, Robert, Ramsauer, Michaela, Dominik, Julian, Mittmann, Laura A., Canis, Martin, Kanse, Sandip, Sperandio, Markus, Krombach, Fritz, Reichel, Christoph A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485676/
https://www.ncbi.nlm.nih.gov/pubmed/32703799
http://dx.doi.org/10.3324/haematol.2019.226241
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author Zuchtriegel, Gabriele
Uhl, Bernd
Pick, Robert
Ramsauer, Michaela
Dominik, Julian
Mittmann, Laura A.
Canis, Martin
Kanse, Sandip
Sperandio, Markus
Krombach, Fritz
Reichel, Christoph A.
author_facet Zuchtriegel, Gabriele
Uhl, Bernd
Pick, Robert
Ramsauer, Michaela
Dominik, Julian
Mittmann, Laura A.
Canis, Martin
Kanse, Sandip
Sperandio, Markus
Krombach, Fritz
Reichel, Christoph A.
author_sort Zuchtriegel, Gabriele
collection PubMed
description The recruitment of neutrophils from the microvasculature to the site of injury or infection represents a key event in the inflammatory response. Vitronectin (VN) is a multifunctional macromolecule abundantly present in blood and extracellular matrix. The role of this glycoprotein in the extravasation process of circulating neutrophils remains elusive. Employing advanced in vivo/ex vivo imaging techniques in different mouse models as well as in vitro methods, we uncovered a previously unrecognized function of VN in the transition of dynamic to static intravascular interactions of neutrophils with microvascular endothelial cells. These distinct properties of VN require the heteromerization of this glycoprotein with plasminogen activator inhibitor-1 (PAI- 1) on the activated venular endothelium and subsequent interactions of this protein complex with the scavenger receptor low-density lipoprotein receptor-related protein-1 on intravascularly adhering neutrophils. This induces p38 mitogen-activated protein kinases-dependent intracellular signaling events which, in turn, regulates the proper clustering of the b2 integrin lymphocyte function associated antigen-1 on the surface of these immune cells. As a consequence of this molecular interplay, neutrophils become able to stabilize their adhesion to the microvascular endothelium and, subsequently, to extravasate to the perivascular tissue. Hence, endothelial-bound VN-PAI-1 heteromers stabilize intravascular adhesion of neutrophils by coordinating b2 integrin clustering on the surface of these immune cells, thereby effectively controlling neutrophil trafficking to inflamed tissue. Targeting this protein complex might be beneficial for the prevention and treatment of inflammatory pathologies.
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spelling pubmed-84856762021-10-18 Vitronectin stabilizes intravascular adhesion of neutrophils by coordinating b2 integrin clustering Zuchtriegel, Gabriele Uhl, Bernd Pick, Robert Ramsauer, Michaela Dominik, Julian Mittmann, Laura A. Canis, Martin Kanse, Sandip Sperandio, Markus Krombach, Fritz Reichel, Christoph A. Haematologica Article The recruitment of neutrophils from the microvasculature to the site of injury or infection represents a key event in the inflammatory response. Vitronectin (VN) is a multifunctional macromolecule abundantly present in blood and extracellular matrix. The role of this glycoprotein in the extravasation process of circulating neutrophils remains elusive. Employing advanced in vivo/ex vivo imaging techniques in different mouse models as well as in vitro methods, we uncovered a previously unrecognized function of VN in the transition of dynamic to static intravascular interactions of neutrophils with microvascular endothelial cells. These distinct properties of VN require the heteromerization of this glycoprotein with plasminogen activator inhibitor-1 (PAI- 1) on the activated venular endothelium and subsequent interactions of this protein complex with the scavenger receptor low-density lipoprotein receptor-related protein-1 on intravascularly adhering neutrophils. This induces p38 mitogen-activated protein kinases-dependent intracellular signaling events which, in turn, regulates the proper clustering of the b2 integrin lymphocyte function associated antigen-1 on the surface of these immune cells. As a consequence of this molecular interplay, neutrophils become able to stabilize their adhesion to the microvascular endothelium and, subsequently, to extravasate to the perivascular tissue. Hence, endothelial-bound VN-PAI-1 heteromers stabilize intravascular adhesion of neutrophils by coordinating b2 integrin clustering on the surface of these immune cells, thereby effectively controlling neutrophil trafficking to inflamed tissue. Targeting this protein complex might be beneficial for the prevention and treatment of inflammatory pathologies. Fondazione Ferrata Storti 2020-07-23 /pmc/articles/PMC8485676/ /pubmed/32703799 http://dx.doi.org/10.3324/haematol.2019.226241 Text en Copyright© 2021 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Zuchtriegel, Gabriele
Uhl, Bernd
Pick, Robert
Ramsauer, Michaela
Dominik, Julian
Mittmann, Laura A.
Canis, Martin
Kanse, Sandip
Sperandio, Markus
Krombach, Fritz
Reichel, Christoph A.
Vitronectin stabilizes intravascular adhesion of neutrophils by coordinating b2 integrin clustering
title Vitronectin stabilizes intravascular adhesion of neutrophils by coordinating b2 integrin clustering
title_full Vitronectin stabilizes intravascular adhesion of neutrophils by coordinating b2 integrin clustering
title_fullStr Vitronectin stabilizes intravascular adhesion of neutrophils by coordinating b2 integrin clustering
title_full_unstemmed Vitronectin stabilizes intravascular adhesion of neutrophils by coordinating b2 integrin clustering
title_short Vitronectin stabilizes intravascular adhesion of neutrophils by coordinating b2 integrin clustering
title_sort vitronectin stabilizes intravascular adhesion of neutrophils by coordinating b2 integrin clustering
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485676/
https://www.ncbi.nlm.nih.gov/pubmed/32703799
http://dx.doi.org/10.3324/haematol.2019.226241
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