Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
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
_version_ 1782288236445433856
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
work_keys_str_mv AT stadtmannanika thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT germenagiulia thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT blockhelena thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT borasmark thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT rossaintjan thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT sunddprithu thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT lefortcraig thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT fishercharlesi thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT buscherkonrad thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT gelschefarthbernadette thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT urzainquiana thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT gerkevolker thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT leyklaus thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT zarbockalexander thepsgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT stadtmannanika psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT germenagiulia psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT blockhelena psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT borasmark psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT rossaintjan psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT sunddprithu psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT lefortcraig psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT fishercharlesi psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT buscherkonrad psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT gelschefarthbernadette psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT urzainquiana psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT gerkevolker psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT leyklaus psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow
AT zarbockalexander psgl1lselectinsignalingcomplexregulatesneutrophiladhesionunderflow