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The PSGL-1–L-selectin signaling complex regulates neutrophil adhesion under flow
Neutrophils are recruited from the blood to sites of inflammation, where they contribute to immune defense but may also cause tissue damage. During inflammation, neutrophils roll along the microvascular endothelium before arresting and transmigrating. Arrest requires conformational activation of the...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804951/ https://www.ncbi.nlm.nih.gov/pubmed/24127491 http://dx.doi.org/10.1084/jem.20130664 |
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author | Stadtmann, Anika Germena, Giulia Block, Helena Boras, Mark Rossaint, Jan Sundd, Prithu Lefort, Craig Fisher, Charles I. Buscher, Konrad Gelschefarth, Bernadette Urzainqui, Ana Gerke, Volker Ley, Klaus Zarbock, Alexander |
author_facet | Stadtmann, Anika Germena, Giulia Block, Helena Boras, Mark Rossaint, Jan Sundd, Prithu Lefort, Craig Fisher, Charles I. Buscher, Konrad Gelschefarth, Bernadette Urzainqui, Ana Gerke, Volker Ley, Klaus Zarbock, Alexander |
author_sort | Stadtmann, Anika |
collection | PubMed |
description | Neutrophils are recruited from the blood to sites of inflammation, where they contribute to immune defense but may also cause tissue damage. During inflammation, neutrophils roll along the microvascular endothelium before arresting and transmigrating. Arrest requires conformational activation of the integrin lymphocyte function–associated antigen 1 (LFA-1), which can be induced by selectin engagement. Here, we demonstrate that a subset of P-selectin glycoprotein ligand-1 (PSGL-1) molecules is constitutively associated with L-selectin. Although this association does not require the known lectin-like interaction between L-selectin and PSGL-1, the signaling output is dependent on this interaction and the cytoplasmic tail of L-selectin. The PSGL-1–L-selectin complex signals through Src family kinases, ITAM domain–containing adaptor proteins, and other kinases to ultimately result in LFA-1 activation. The PSGL-1–L-selectin complex–induced signaling effects on neutrophil slow rolling and recruitment in vivo demonstrate the functional importance of this pathway. We conclude that this is a signaling complex specialized for sensing adhesion under flow. |
format | Online Article Text |
id | pubmed-3804951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-38049512014-04-21 The PSGL-1–L-selectin signaling complex regulates neutrophil adhesion under flow Stadtmann, Anika Germena, Giulia Block, Helena Boras, Mark Rossaint, Jan Sundd, Prithu Lefort, Craig Fisher, Charles I. Buscher, Konrad Gelschefarth, Bernadette Urzainqui, Ana Gerke, Volker Ley, Klaus Zarbock, Alexander J Exp Med Brief Definitive Report Neutrophils are recruited from the blood to sites of inflammation, where they contribute to immune defense but may also cause tissue damage. During inflammation, neutrophils roll along the microvascular endothelium before arresting and transmigrating. Arrest requires conformational activation of the integrin lymphocyte function–associated antigen 1 (LFA-1), which can be induced by selectin engagement. Here, we demonstrate that a subset of P-selectin glycoprotein ligand-1 (PSGL-1) molecules is constitutively associated with L-selectin. Although this association does not require the known lectin-like interaction between L-selectin and PSGL-1, the signaling output is dependent on this interaction and the cytoplasmic tail of L-selectin. The PSGL-1–L-selectin complex signals through Src family kinases, ITAM domain–containing adaptor proteins, and other kinases to ultimately result in LFA-1 activation. The PSGL-1–L-selectin complex–induced signaling effects on neutrophil slow rolling and recruitment in vivo demonstrate the functional importance of this pathway. We conclude that this is a signaling complex specialized for sensing adhesion under flow. The Rockefeller University Press 2013-10-21 /pmc/articles/PMC3804951/ /pubmed/24127491 http://dx.doi.org/10.1084/jem.20130664 Text en © 2013 Stadtmann et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Stadtmann, Anika Germena, Giulia Block, Helena Boras, Mark Rossaint, Jan Sundd, Prithu Lefort, Craig Fisher, Charles I. Buscher, Konrad Gelschefarth, Bernadette Urzainqui, Ana Gerke, Volker Ley, Klaus Zarbock, Alexander The PSGL-1–L-selectin signaling complex regulates neutrophil adhesion under flow |
title | The PSGL-1–L-selectin signaling complex regulates neutrophil adhesion under flow |
title_full | The PSGL-1–L-selectin signaling complex regulates neutrophil adhesion under flow |
title_fullStr | The PSGL-1–L-selectin signaling complex regulates neutrophil adhesion under flow |
title_full_unstemmed | The PSGL-1–L-selectin signaling complex regulates neutrophil adhesion under flow |
title_short | The PSGL-1–L-selectin signaling complex regulates neutrophil adhesion under flow |
title_sort | psgl-1–l-selectin signaling complex regulates neutrophil adhesion under flow |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804951/ https://www.ncbi.nlm.nih.gov/pubmed/24127491 http://dx.doi.org/10.1084/jem.20130664 |
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