Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells

LFA-1 is a leukocyte specific β2 integrin that plays a major role in regulating adhesion and migration of different immune cells. Recent data suggest that LFA-1 on mature dendritic cells (mDCs) may function as a chemokine-inducible anchor during homing of DCs through the afferent lymphatics into the...

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Autores: Borgman, Kyra J., Zanten, Thomas S. van, Manzo, Carlo, Cabezón, Raquel, Cambi, Alessandra, Benítez-Ribas, Daniel, Garcia-Parajo, Maria F.
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/24864
Acceso en línea:https://hdl.handle.net/2117/24864
https://dx.doi.org/10.1371/journal.pone.0099589
Access Level:acceso abierto
Palabra clave:Chemokines
chemokine
integrin
intercellular adhesion molecule 1
lymphocyte function associated antigen 1
monocyte chemotactic protein 5
Biologia
Àrees temàtiques de la UPC::Ciències de la salut
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spelling Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic CellsBorgman, Kyra J.Zanten, Thomas S. vanManzo, CarloCabezón, RaquelCambi, AlessandraBenítez-Ribas, DanielGarcia-Parajo, Maria F.Chemokineschemokineintegrinintercellular adhesion molecule 1lymphocyte function associated antigen 1monocyte chemotactic protein 5BiologiaÀrees temàtiques de la UPC::Ciències de la salutLFA-1 is a leukocyte specific β2 integrin that plays a major role in regulating adhesion and migration of different immune cells. Recent data suggest that LFA-1 on mature dendritic cells (mDCs) may function as a chemokine-inducible anchor during homing of DCs through the afferent lymphatics into the lymph nodes, by transiently switching its molecular conformational state. However, the role of LFA-1 mobility in this process is not yet known, despite that the importance of lateral organization and dynamics for LFA-1-mediated adhesion regulation is broadly recognized. Using single particle tracking approaches we here show that LFA-1 exhibits higher mobility on resting mDCs compared to monocytes. Lymphoid chemokine CCL21 stimulation of the LFA-1 high affinity state on mDCs, led to a significant reduction of mobility and an increase on the fraction of stationary receptors, consistent with re-activation of the receptor. Addition of soluble monomeric ICAM-1 in the presence of CCL21 did not alter the diffusion profile of LFA-1 while soluble ICAM-1 nano-aggregates in the presence of CCL21 further reduced LFA-1 mobility and readily bound to the receptor. Overall, our results emphasize the importance of LFA-1 lateral mobility across the membrane on the regulation of integrin activation and its function as adhesion receptor. Importantly, our data show that chemokines alone are not sufficient to trigger the high affinity state of the integrin based on the strict definition that affinity refers to the adhesion capacity of a single receptor to its ligand in solution. Instead our data indicate that nanoclustering of the receptor, induced by multi-ligand binding, is required to maintain stable cell adhesion once LFA-1 high affinity state is transiently triggered by inside-out signals.Peer ReviewedPLOS20142014-06-1920142014-11-27journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/24864https://dx.doi.org/10.1371/journal.pone.009958924945611reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)InglésengEuropean Commission http://dx.doi.org/10.13039/100011102 Seventh Framework Programme 288263 Advanced photonic antenna tools for biosensing and cellular nanoimagingopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/248642026-05-27T15:37:01Z
dc.title.none.fl_str_mv Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells
title Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells
spellingShingle Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells
Borgman, Kyra J.
Chemokines
chemokine
integrin
intercellular adhesion molecule 1
lymphocyte function associated antigen 1
monocyte chemotactic protein 5
Biologia
Àrees temàtiques de la UPC::Ciències de la salut
title_short Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells
title_full Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells
title_fullStr Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells
title_full_unstemmed Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells
title_sort Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells
dc.creator.none.fl_str_mv Borgman, Kyra J.
Zanten, Thomas S. van
Manzo, Carlo
Cabezón, Raquel
Cambi, Alessandra
Benítez-Ribas, Daniel
Garcia-Parajo, Maria F.
author Borgman, Kyra J.
author_facet Borgman, Kyra J.
Zanten, Thomas S. van
Manzo, Carlo
Cabezón, Raquel
Cambi, Alessandra
Benítez-Ribas, Daniel
Garcia-Parajo, Maria F.
author_role author
author2 Zanten, Thomas S. van
Manzo, Carlo
Cabezón, Raquel
Cambi, Alessandra
Benítez-Ribas, Daniel
Garcia-Parajo, Maria F.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Chemokines
chemokine
integrin
intercellular adhesion molecule 1
lymphocyte function associated antigen 1
monocyte chemotactic protein 5
Biologia
Àrees temàtiques de la UPC::Ciències de la salut
topic Chemokines
chemokine
integrin
intercellular adhesion molecule 1
lymphocyte function associated antigen 1
monocyte chemotactic protein 5
Biologia
Àrees temàtiques de la UPC::Ciències de la salut
description LFA-1 is a leukocyte specific β2 integrin that plays a major role in regulating adhesion and migration of different immune cells. Recent data suggest that LFA-1 on mature dendritic cells (mDCs) may function as a chemokine-inducible anchor during homing of DCs through the afferent lymphatics into the lymph nodes, by transiently switching its molecular conformational state. However, the role of LFA-1 mobility in this process is not yet known, despite that the importance of lateral organization and dynamics for LFA-1-mediated adhesion regulation is broadly recognized. Using single particle tracking approaches we here show that LFA-1 exhibits higher mobility on resting mDCs compared to monocytes. Lymphoid chemokine CCL21 stimulation of the LFA-1 high affinity state on mDCs, led to a significant reduction of mobility and an increase on the fraction of stationary receptors, consistent with re-activation of the receptor. Addition of soluble monomeric ICAM-1 in the presence of CCL21 did not alter the diffusion profile of LFA-1 while soluble ICAM-1 nano-aggregates in the presence of CCL21 further reduced LFA-1 mobility and readily bound to the receptor. Overall, our results emphasize the importance of LFA-1 lateral mobility across the membrane on the regulation of integrin activation and its function as adhesion receptor. Importantly, our data show that chemokines alone are not sufficient to trigger the high affinity state of the integrin based on the strict definition that affinity refers to the adhesion capacity of a single receptor to its ligand in solution. Instead our data indicate that nanoclustering of the receptor, induced by multi-ligand binding, is required to maintain stable cell adhesion once LFA-1 high affinity state is transiently triggered by inside-out signals.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-06-19
2014
2014-11-27
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/24864
https://dx.doi.org/10.1371/journal.pone.0099589
24945611
url https://hdl.handle.net/2117/24864
https://dx.doi.org/10.1371/journal.pone.0099589
identifier_str_mv 24945611
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/100011102 Seventh Framework Programme 288263 Advanced photonic antenna tools for biosensing and cellular nanoimaging
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv PLOS
publisher.none.fl_str_mv PLOS
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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