Paracrine regulation of megakaryo/thrombopoiesis by macrophages

Autores
D'Atri, Lina Paola; Pozner, Roberto Gabriel; Nahmod, Karen Amelia; Landoni, Verónica Inés; Isturiz, Martín Amadeo; Negrotto, Soledad; Schattner, Mirta Ana
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: Megakaryo/thrombopoiesis is a complex process regulated by multiple signals provided by the bone marrow microenvironment. Because macrophages are relevant components of the bone marrow stroma and their activation induces an upregulation of molecules that can regulate hematopoiesis, we analyzed the impact of these cells on the control of megakaryocyte development and platelet biogenesis. Materials and Methods: The different stages of megakaryo/thrombopoiesis were analyzed by flow cytometry using an in vitro model of human cord blood CD34+ cells stimulated with thrombopoietin in either a transwell system or conditioned media from monocyte-derived macrophages isolated from peripheral blood. Cytokines secreted from macrophages were characterized by protein array and enzyme-linked immunosorbent assay. Results: Resting macrophages released soluble factors that promoted megakaryocyte growth, cell ploidy, a size increase, proplatelet production, and platelet release. Lipopolysaccharide stimulation triggered the secretion of cytokines that exerted opposite effects together with a dramatic switch of CD34+ commitment to the megakaryocytic lineage toward the myeloid lineage. Neutralization of interleukin-8 released by stimulated macrophages partially reversed the inhibition of megakaryocyte growth. Activation of nuclear factor κB had a major role in the synthesis of molecules involved in the megakaryocyte inhibition mediated by lipopolysaccharide-stimulated macrophages. Conclusions: Our study extends our understanding about the role of the bone marrow microenvironment in the regulation of megakaryo/thrombopoiesis by showing that soluble factors derived from macrophages positively or negatively control megakaryocyte growth, differentiation, maturation, and their ability to produce platelets. © 2011 ISEH - Society for Hematology and Stem Cells.
Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Nahmod, Karen Amelia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Materia
Megacariocyte
Thrombosis
Thrombopoiesis
Macrophages
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:11336/52897
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/52897
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Paracrine regulation of megakaryo/thrombopoiesis by macrophagesD'Atri, Lina PaolaPozner, Roberto GabrielNahmod, Karen AmeliaLandoni, Verónica InésIsturiz, Martín AmadeoNegrotto, SoledadSchattner, Mirta AnaMegacariocyteThrombosisThrombopoiesisMacrophageshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Objective: Megakaryo/thrombopoiesis is a complex process regulated by multiple signals provided by the bone marrow microenvironment. Because macrophages are relevant components of the bone marrow stroma and their activation induces an upregulation of molecules that can regulate hematopoiesis, we analyzed the impact of these cells on the control of megakaryocyte development and platelet biogenesis. Materials and Methods: The different stages of megakaryo/thrombopoiesis were analyzed by flow cytometry using an in vitro model of human cord blood CD34+ cells stimulated with thrombopoietin in either a transwell system or conditioned media from monocyte-derived macrophages isolated from peripheral blood. Cytokines secreted from macrophages were characterized by protein array and enzyme-linked immunosorbent assay. Results: Resting macrophages released soluble factors that promoted megakaryocyte growth, cell ploidy, a size increase, proplatelet production, and platelet release. Lipopolysaccharide stimulation triggered the secretion of cytokines that exerted opposite effects together with a dramatic switch of CD34+ commitment to the megakaryocytic lineage toward the myeloid lineage. Neutralization of interleukin-8 released by stimulated macrophages partially reversed the inhibition of megakaryocyte growth. Activation of nuclear factor κB had a major role in the synthesis of molecules involved in the megakaryocyte inhibition mediated by lipopolysaccharide-stimulated macrophages. Conclusions: Our study extends our understanding about the role of the bone marrow microenvironment in the regulation of megakaryo/thrombopoiesis by showing that soluble factors derived from macrophages positively or negatively control megakaryocyte growth, differentiation, maturation, and their ability to produce platelets. © 2011 ISEH - Society for Hematology and Stem Cells.Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Nahmod, Karen Amelia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaElsevier Science Inc2011-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/52897D'Atri, Lina Paola; Pozner, Roberto Gabriel; Nahmod, Karen Amelia; Landoni, Verónica Inés; Isturiz, Martín Amadeo; et al.; Paracrine regulation of megakaryo/thrombopoiesis by macrophages; Elsevier Science Inc; Experimental Hematology; 39; 7; 7-2011; 763-7720301-472XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.exphem.2011.03.009info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0301472X11001743info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:43Zoai:ri.conicet.gov.ar:11336/52897instacron: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:34982025-09-03 09:44:43.951CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Paracrine regulation of megakaryo/thrombopoiesis by macrophages
title Paracrine regulation of megakaryo/thrombopoiesis by macrophages
spellingShingle Paracrine regulation of megakaryo/thrombopoiesis by macrophages
D'Atri, Lina Paola
Megacariocyte
Thrombosis
Thrombopoiesis
Macrophages
title_short Paracrine regulation of megakaryo/thrombopoiesis by macrophages
title_full Paracrine regulation of megakaryo/thrombopoiesis by macrophages
title_fullStr Paracrine regulation of megakaryo/thrombopoiesis by macrophages
title_full_unstemmed Paracrine regulation of megakaryo/thrombopoiesis by macrophages
title_sort Paracrine regulation of megakaryo/thrombopoiesis by macrophages
dc.creator.none.fl_str_mv D'Atri, Lina Paola
Pozner, Roberto Gabriel
Nahmod, Karen Amelia
Landoni, Verónica Inés
Isturiz, Martín Amadeo
Negrotto, Soledad
Schattner, Mirta Ana
author D'Atri, Lina Paola
author_facet D'Atri, Lina Paola
Pozner, Roberto Gabriel
Nahmod, Karen Amelia
Landoni, Verónica Inés
Isturiz, Martín Amadeo
Negrotto, Soledad
Schattner, Mirta Ana
author_role author
author2 Pozner, Roberto Gabriel
Nahmod, Karen Amelia
Landoni, Verónica Inés
Isturiz, Martín Amadeo
Negrotto, Soledad
Schattner, Mirta Ana
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Megacariocyte
Thrombosis
Thrombopoiesis
Macrophages
topic Megacariocyte
Thrombosis
Thrombopoiesis
Macrophages
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: Megakaryo/thrombopoiesis is a complex process regulated by multiple signals provided by the bone marrow microenvironment. Because macrophages are relevant components of the bone marrow stroma and their activation induces an upregulation of molecules that can regulate hematopoiesis, we analyzed the impact of these cells on the control of megakaryocyte development and platelet biogenesis. Materials and Methods: The different stages of megakaryo/thrombopoiesis were analyzed by flow cytometry using an in vitro model of human cord blood CD34+ cells stimulated with thrombopoietin in either a transwell system or conditioned media from monocyte-derived macrophages isolated from peripheral blood. Cytokines secreted from macrophages were characterized by protein array and enzyme-linked immunosorbent assay. Results: Resting macrophages released soluble factors that promoted megakaryocyte growth, cell ploidy, a size increase, proplatelet production, and platelet release. Lipopolysaccharide stimulation triggered the secretion of cytokines that exerted opposite effects together with a dramatic switch of CD34+ commitment to the megakaryocytic lineage toward the myeloid lineage. Neutralization of interleukin-8 released by stimulated macrophages partially reversed the inhibition of megakaryocyte growth. Activation of nuclear factor κB had a major role in the synthesis of molecules involved in the megakaryocyte inhibition mediated by lipopolysaccharide-stimulated macrophages. Conclusions: Our study extends our understanding about the role of the bone marrow microenvironment in the regulation of megakaryo/thrombopoiesis by showing that soluble factors derived from macrophages positively or negatively control megakaryocyte growth, differentiation, maturation, and their ability to produce platelets. © 2011 ISEH - Society for Hematology and Stem Cells.
Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Nahmod, Karen Amelia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
description Objective: Megakaryo/thrombopoiesis is a complex process regulated by multiple signals provided by the bone marrow microenvironment. Because macrophages are relevant components of the bone marrow stroma and their activation induces an upregulation of molecules that can regulate hematopoiesis, we analyzed the impact of these cells on the control of megakaryocyte development and platelet biogenesis. Materials and Methods: The different stages of megakaryo/thrombopoiesis were analyzed by flow cytometry using an in vitro model of human cord blood CD34+ cells stimulated with thrombopoietin in either a transwell system or conditioned media from monocyte-derived macrophages isolated from peripheral blood. Cytokines secreted from macrophages were characterized by protein array and enzyme-linked immunosorbent assay. Results: Resting macrophages released soluble factors that promoted megakaryocyte growth, cell ploidy, a size increase, proplatelet production, and platelet release. Lipopolysaccharide stimulation triggered the secretion of cytokines that exerted opposite effects together with a dramatic switch of CD34+ commitment to the megakaryocytic lineage toward the myeloid lineage. Neutralization of interleukin-8 released by stimulated macrophages partially reversed the inhibition of megakaryocyte growth. Activation of nuclear factor κB had a major role in the synthesis of molecules involved in the megakaryocyte inhibition mediated by lipopolysaccharide-stimulated macrophages. Conclusions: Our study extends our understanding about the role of the bone marrow microenvironment in the regulation of megakaryo/thrombopoiesis by showing that soluble factors derived from macrophages positively or negatively control megakaryocyte growth, differentiation, maturation, and their ability to produce platelets. © 2011 ISEH - Society for Hematology and Stem Cells.
publishDate 2011
dc.date.none.fl_str_mv 2011-07
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/11336/52897
D'Atri, Lina Paola; Pozner, Roberto Gabriel; Nahmod, Karen Amelia; Landoni, Verónica Inés; Isturiz, Martín Amadeo; et al.; Paracrine regulation of megakaryo/thrombopoiesis by macrophages; Elsevier Science Inc; Experimental Hematology; 39; 7; 7-2011; 763-772
0301-472X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52897
identifier_str_mv D'Atri, Lina Paola; Pozner, Roberto Gabriel; Nahmod, Karen Amelia; Landoni, Verónica Inés; Isturiz, Martín Amadeo; et al.; Paracrine regulation of megakaryo/thrombopoiesis by macrophages; Elsevier Science Inc; Experimental Hematology; 39; 7; 7-2011; 763-772
0301-472X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exphem.2011.03.009
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0301472X11001743
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
dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science 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 13.13397

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