Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage

Autores
D'Atri, Lina Paola; Etulain, Julia; Rivadeneyra, Leonardo; Lapponi, María José; Centurion, M.; Cheng, K.; Yin, H.; Schattner, Mirta Ana
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: In addition to their key role in hemostasis, platelets and megakaryocytes regulate immune and inflammatory responses, in part through their expression of Toll-like receptors (TLRs). Among the TLRs, TLR3 recognizes dsRNA associated with viral infection. Thrombocytopenia is a frequent complication of viral infection. However, the expression and functionality of TLR3 in megakaryocytes and platelets is not yet well understood. Objective: To study the expression and functionality of TLR3 in the megakaryocytic lineage. Methods and results: RT-PCR, flow cytometric and immunofluorescence assays showed that TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets. Immunoblotting assays showed that stimulation of megakaryocytes with two synthetic agonists of TLR3, Poly(I:C) and Poly(A:U), activated the nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-related kinase (ERK)1/2 and p38 pathways. TLR3-megakaryocyte activation resulted in reduced platelet production in vitro and interferon-β release through the PI3K-Akt and NF-κB signaling pathways. TLR3 ligands potentiated the aggregation mediated by classic platelet agonists. This effect was also observed for ATP release, but not for P-selectin or CD40L membrane exposure, indicating that TLR3 activation was not involved in α-granule release. In addition, TLR3 agonists induced activation of the NF-κB, PI3K-Akt and ERK1/2 pathways in platelets. Reductions in platelet production and platelet fibrinogen binding mediated by Poly(I:C) or Poly(A:U) were prevented by the presence of an inhibitor of the TLR3-dsRNA complex. Conclusions: Our findings indicate that functional TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets, and suggest a potential role for this receptor in the megakaryopoiesis/thrombopoiesis alterations that occur in viral infections.
Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rivadeneyra, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lapponi, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Centurion, M.. Ciudad Autónoma de Buenos Aires. Hospital Bernardino Rivadavia ; Argentina
Fil: Cheng, K.. Tsinghua University; China
Fil: Yin, H.. Tsinghua University; China. State University of Colorado Boulder; Estados Unidos
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
Interferon-Beta
Megakaryocytes
Nf-Kappa B
Platelets
Toll-Like Receptor&Nbsp;3
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/38495
Acceder
id CONICETDig_616a18f09cf465fea2d5cdf18832c00f
oai_identifier_str oai:ri.conicet.gov.ar:11336/38495
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineageD'Atri, Lina PaolaEtulain, JuliaRivadeneyra, LeonardoLapponi, María JoséCenturion, M.Cheng, K.Yin, H.Schattner, Mirta AnaInterferon-BetaMegakaryocytesNf-Kappa BPlateletsToll-Like Receptor&Nbsp;3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: In addition to their key role in hemostasis, platelets and megakaryocytes regulate immune and inflammatory responses, in part through their expression of Toll-like receptors (TLRs). Among the TLRs, TLR3 recognizes dsRNA associated with viral infection. Thrombocytopenia is a frequent complication of viral infection. However, the expression and functionality of TLR3 in megakaryocytes and platelets is not yet well understood. Objective: To study the expression and functionality of TLR3 in the megakaryocytic lineage. Methods and results: RT-PCR, flow cytometric and immunofluorescence assays showed that TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets. Immunoblotting assays showed that stimulation of megakaryocytes with two synthetic agonists of TLR3, Poly(I:C) and Poly(A:U), activated the nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-related kinase (ERK)1/2 and p38 pathways. TLR3-megakaryocyte activation resulted in reduced platelet production in vitro and interferon-β release through the PI3K-Akt and NF-κB signaling pathways. TLR3 ligands potentiated the aggregation mediated by classic platelet agonists. This effect was also observed for ATP release, but not for P-selectin or CD40L membrane exposure, indicating that TLR3 activation was not involved in α-granule release. In addition, TLR3 agonists induced activation of the NF-κB, PI3K-Akt and ERK1/2 pathways in platelets. Reductions in platelet production and platelet fibrinogen binding mediated by Poly(I:C) or Poly(A:U) were prevented by the presence of an inhibitor of the TLR3-dsRNA complex. Conclusions: Our findings indicate that functional TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets, and suggest a potential role for this receptor in the megakaryopoiesis/thrombopoiesis alterations that occur in viral infections.Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rivadeneyra, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Lapponi, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Centurion, M.. Ciudad Autónoma de Buenos Aires. Hospital Bernardino Rivadavia ; ArgentinaFil: Cheng, K.. Tsinghua University; ChinaFil: Yin, H.. Tsinghua University; China. State University of Colorado Boulder; Estados UnidosFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaWiley Blackwell Publishing, Inc2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38495D'Atri, Lina Paola; Etulain, Julia; Rivadeneyra, Leonardo; Lapponi, María José; Centurion, M.; et al.; Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage; Wiley Blackwell Publishing, Inc; Journal of Thrombosis and Haemostasis; 13; 5; 5-2015; 839-8501538-7933CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/jth.12842/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/jth.12842info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:23:05Zoai:ri.conicet.gov.ar:11336/38495instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:23:05.731CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage
title Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage
spellingShingle Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage
D'Atri, Lina Paola
Interferon-Beta
Megakaryocytes
Nf-Kappa B
Platelets
Toll-Like Receptor&Nbsp;3
title_short Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage
title_full Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage
title_fullStr Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage
title_full_unstemmed Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage
title_sort Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage
dc.creator.none.fl_str_mv D'Atri, Lina Paola
Etulain, Julia
Rivadeneyra, Leonardo
Lapponi, María José
Centurion, M.
Cheng, K.
Yin, H.
Schattner, Mirta Ana
author D'Atri, Lina Paola
author_facet D'Atri, Lina Paola
Etulain, Julia
Rivadeneyra, Leonardo
Lapponi, María José
Centurion, M.
Cheng, K.
Yin, H.
Schattner, Mirta Ana
author_role author
author2 Etulain, Julia
Rivadeneyra, Leonardo
Lapponi, María José
Centurion, M.
Cheng, K.
Yin, H.
Schattner, Mirta Ana
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Interferon-Beta
Megakaryocytes
Nf-Kappa B
Platelets
Toll-Like Receptor&Nbsp;3
topic Interferon-Beta
Megakaryocytes
Nf-Kappa B
Platelets
Toll-Like Receptor&Nbsp;3
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: In addition to their key role in hemostasis, platelets and megakaryocytes regulate immune and inflammatory responses, in part through their expression of Toll-like receptors (TLRs). Among the TLRs, TLR3 recognizes dsRNA associated with viral infection. Thrombocytopenia is a frequent complication of viral infection. However, the expression and functionality of TLR3 in megakaryocytes and platelets is not yet well understood. Objective: To study the expression and functionality of TLR3 in the megakaryocytic lineage. Methods and results: RT-PCR, flow cytometric and immunofluorescence assays showed that TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets. Immunoblotting assays showed that stimulation of megakaryocytes with two synthetic agonists of TLR3, Poly(I:C) and Poly(A:U), activated the nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-related kinase (ERK)1/2 and p38 pathways. TLR3-megakaryocyte activation resulted in reduced platelet production in vitro and interferon-β release through the PI3K-Akt and NF-κB signaling pathways. TLR3 ligands potentiated the aggregation mediated by classic platelet agonists. This effect was also observed for ATP release, but not for P-selectin or CD40L membrane exposure, indicating that TLR3 activation was not involved in α-granule release. In addition, TLR3 agonists induced activation of the NF-κB, PI3K-Akt and ERK1/2 pathways in platelets. Reductions in platelet production and platelet fibrinogen binding mediated by Poly(I:C) or Poly(A:U) were prevented by the presence of an inhibitor of the TLR3-dsRNA complex. Conclusions: Our findings indicate that functional TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets, and suggest a potential role for this receptor in the megakaryopoiesis/thrombopoiesis alterations that occur in viral infections.
Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rivadeneyra, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lapponi, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Centurion, M.. Ciudad Autónoma de Buenos Aires. Hospital Bernardino Rivadavia ; Argentina
Fil: Cheng, K.. Tsinghua University; China
Fil: Yin, H.. Tsinghua University; China. State University of Colorado Boulder; Estados Unidos
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Background: In addition to their key role in hemostasis, platelets and megakaryocytes regulate immune and inflammatory responses, in part through their expression of Toll-like receptors (TLRs). Among the TLRs, TLR3 recognizes dsRNA associated with viral infection. Thrombocytopenia is a frequent complication of viral infection. However, the expression and functionality of TLR3 in megakaryocytes and platelets is not yet well understood. Objective: To study the expression and functionality of TLR3 in the megakaryocytic lineage. Methods and results: RT-PCR, flow cytometric and immunofluorescence assays showed that TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets. Immunoblotting assays showed that stimulation of megakaryocytes with two synthetic agonists of TLR3, Poly(I:C) and Poly(A:U), activated the nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-related kinase (ERK)1/2 and p38 pathways. TLR3-megakaryocyte activation resulted in reduced platelet production in vitro and interferon-β release through the PI3K-Akt and NF-κB signaling pathways. TLR3 ligands potentiated the aggregation mediated by classic platelet agonists. This effect was also observed for ATP release, but not for P-selectin or CD40L membrane exposure, indicating that TLR3 activation was not involved in α-granule release. In addition, TLR3 agonists induced activation of the NF-κB, PI3K-Akt and ERK1/2 pathways in platelets. Reductions in platelet production and platelet fibrinogen binding mediated by Poly(I:C) or Poly(A:U) were prevented by the presence of an inhibitor of the TLR3-dsRNA complex. Conclusions: Our findings indicate that functional TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets, and suggest a potential role for this receptor in the megakaryopoiesis/thrombopoiesis alterations that occur in viral infections.
publishDate 2015
dc.date.none.fl_str_mv 2015-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/38495
D'Atri, Lina Paola; Etulain, Julia; Rivadeneyra, Leonardo; Lapponi, María José; Centurion, M.; et al.; Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage; Wiley Blackwell Publishing, Inc; Journal of Thrombosis and Haemostasis; 13; 5; 5-2015; 839-850
1538-7933
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38495
identifier_str_mv D'Atri, Lina Paola; Etulain, Julia; Rivadeneyra, Leonardo; Lapponi, María José; Centurion, M.; et al.; Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage; Wiley Blackwell Publishing, Inc; Journal of Thrombosis and Haemostasis; 13; 5; 5-2015; 839-850
1538-7933
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/jth.12842/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1111/jth.12842
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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