Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome

Autores
Ramos, Maria Victoria; Auvynet, Constance; Poupel, Lucie; Rodero, Mathieu; Mejias, María Pilar; Panek, Cecilia Analía; Vanzulli, Silvia; Combadiere, Christophe; Palermo, Marina Sandra
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Shiga toxin (Stx)producing Escherichia coli is the main etiological agent that causes hemolytic uremic syndrome (HUS), a microangiopathic disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Although direct cytotoxic effects on endothelial cells by Stx are the primary pathogenic event, there is evidence that indicates the inflammatory response mediated by polymorphonuclear neutrophils and monocytes as the key event during HUS development. Because the chemokine receptor CCR1 participates in the pathogenesis of several renal diseases by orchestrating myeloid cell kidney infiltration, we specifically addressed the contribution of CCR1 in a murine model of HUS. We showed that Stx type 2treated CCR1 -/- mice have an increased survival rate associated with less functional and histological renal damage compared with control mice. Stx type 2triggered neutrophilia and monocytosis and polymorphonuclear neutrophil and monocyte renal infiltration were significantly reduced and delayed in CCR1 -/- mice compared with control mice. In addition, the increase of the inflammatory cytokines (tumor necrosis factor-α and IL-6) in plasma was delayed in CCR1 -/- mice compared with control mice. These data demonstrate that CCR1 participates in cell recruitment to the kidney and amplification of the inflammatory response that contributes to HUS development. Blockade of CCR1 could be important to the design of future therapies to restrain the inflammatory response involved in the development of HUS.
Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Auvynet, Constance. Universite Pierre et Marie Curie; Francia. Inserm; Francia
Fil: Poupel, Lucie. Inserm; Francia. Universite Pierre et Marie Curie; Francia
Fil: Rodero, Mathieu. Universite Pierre et Marie Curie; Francia. Inserm; Francia
Fil: Mejias, María Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Panek, Cecilia Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Combadiere, Christophe. Universite Pierre et Marie Curie; Francia. Inserm; Francia
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
Hus
Shiga Toxin
Chemokines
Ccr1
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:11336/91155
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/91155
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndromeRamos, Maria VictoriaAuvynet, ConstancePoupel, LucieRodero, MathieuMejias, María PilarPanek, Cecilia AnalíaVanzulli, SilviaCombadiere, ChristophePalermo, Marina SandraHusShiga ToxinChemokinesCcr1https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Shiga toxin (Stx)producing Escherichia coli is the main etiological agent that causes hemolytic uremic syndrome (HUS), a microangiopathic disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Although direct cytotoxic effects on endothelial cells by Stx are the primary pathogenic event, there is evidence that indicates the inflammatory response mediated by polymorphonuclear neutrophils and monocytes as the key event during HUS development. Because the chemokine receptor CCR1 participates in the pathogenesis of several renal diseases by orchestrating myeloid cell kidney infiltration, we specifically addressed the contribution of CCR1 in a murine model of HUS. We showed that Stx type 2treated CCR1 -/- mice have an increased survival rate associated with less functional and histological renal damage compared with control mice. Stx type 2triggered neutrophilia and monocytosis and polymorphonuclear neutrophil and monocyte renal infiltration were significantly reduced and delayed in CCR1 -/- mice compared with control mice. In addition, the increase of the inflammatory cytokines (tumor necrosis factor-α and IL-6) in plasma was delayed in CCR1 -/- mice compared with control mice. These data demonstrate that CCR1 participates in cell recruitment to the kidney and amplification of the inflammatory response that contributes to HUS development. Blockade of CCR1 could be important to the design of future therapies to restrain the inflammatory response involved in the development of HUS.Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Auvynet, Constance. Universite Pierre et Marie Curie; Francia. Inserm; FranciaFil: Poupel, Lucie. Inserm; Francia. Universite Pierre et Marie Curie; FranciaFil: Rodero, Mathieu. Universite Pierre et Marie Curie; Francia. Inserm; FranciaFil: Mejias, María Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Panek, Cecilia Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Combadiere, Christophe. Universite Pierre et Marie Curie; Francia. Inserm; FranciaFil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaAmerican Society of Investigative Pathology2012-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/91155Ramos, Maria Victoria; Auvynet, Constance; Poupel, Lucie; Rodero, Mathieu; Mejias, María Pilar; et al.; Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome; American Society of Investigative Pathology; American Journal Of Pathology; 180; 3; 3-2012; 1040-10480002-9440CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0002944011010741info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ajpath.2011.11.011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:51Zoai:ri.conicet.gov.ar:11336/91155instacron: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 09:55:51.78CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome
title Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome
spellingShingle Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome
Ramos, Maria Victoria
Hus
Shiga Toxin
Chemokines
Ccr1
title_short Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome
title_full Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome
title_fullStr Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome
title_full_unstemmed Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome
title_sort Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome
dc.creator.none.fl_str_mv Ramos, Maria Victoria
Auvynet, Constance
Poupel, Lucie
Rodero, Mathieu
Mejias, María Pilar
Panek, Cecilia Analía
Vanzulli, Silvia
Combadiere, Christophe
Palermo, Marina Sandra
author Ramos, Maria Victoria
author_facet Ramos, Maria Victoria
Auvynet, Constance
Poupel, Lucie
Rodero, Mathieu
Mejias, María Pilar
Panek, Cecilia Analía
Vanzulli, Silvia
Combadiere, Christophe
Palermo, Marina Sandra
author_role author
author2 Auvynet, Constance
Poupel, Lucie
Rodero, Mathieu
Mejias, María Pilar
Panek, Cecilia Analía
Vanzulli, Silvia
Combadiere, Christophe
Palermo, Marina Sandra
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hus
Shiga Toxin
Chemokines
Ccr1
topic Hus
Shiga Toxin
Chemokines
Ccr1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Shiga toxin (Stx)producing Escherichia coli is the main etiological agent that causes hemolytic uremic syndrome (HUS), a microangiopathic disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Although direct cytotoxic effects on endothelial cells by Stx are the primary pathogenic event, there is evidence that indicates the inflammatory response mediated by polymorphonuclear neutrophils and monocytes as the key event during HUS development. Because the chemokine receptor CCR1 participates in the pathogenesis of several renal diseases by orchestrating myeloid cell kidney infiltration, we specifically addressed the contribution of CCR1 in a murine model of HUS. We showed that Stx type 2treated CCR1 -/- mice have an increased survival rate associated with less functional and histological renal damage compared with control mice. Stx type 2triggered neutrophilia and monocytosis and polymorphonuclear neutrophil and monocyte renal infiltration were significantly reduced and delayed in CCR1 -/- mice compared with control mice. In addition, the increase of the inflammatory cytokines (tumor necrosis factor-α and IL-6) in plasma was delayed in CCR1 -/- mice compared with control mice. These data demonstrate that CCR1 participates in cell recruitment to the kidney and amplification of the inflammatory response that contributes to HUS development. Blockade of CCR1 could be important to the design of future therapies to restrain the inflammatory response involved in the development of HUS.
Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Auvynet, Constance. Universite Pierre et Marie Curie; Francia. Inserm; Francia
Fil: Poupel, Lucie. Inserm; Francia. Universite Pierre et Marie Curie; Francia
Fil: Rodero, Mathieu. Universite Pierre et Marie Curie; Francia. Inserm; Francia
Fil: Mejias, María Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Panek, Cecilia Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Combadiere, Christophe. Universite Pierre et Marie Curie; Francia. Inserm; Francia
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Shiga toxin (Stx)producing Escherichia coli is the main etiological agent that causes hemolytic uremic syndrome (HUS), a microangiopathic disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Although direct cytotoxic effects on endothelial cells by Stx are the primary pathogenic event, there is evidence that indicates the inflammatory response mediated by polymorphonuclear neutrophils and monocytes as the key event during HUS development. Because the chemokine receptor CCR1 participates in the pathogenesis of several renal diseases by orchestrating myeloid cell kidney infiltration, we specifically addressed the contribution of CCR1 in a murine model of HUS. We showed that Stx type 2treated CCR1 -/- mice have an increased survival rate associated with less functional and histological renal damage compared with control mice. Stx type 2triggered neutrophilia and monocytosis and polymorphonuclear neutrophil and monocyte renal infiltration were significantly reduced and delayed in CCR1 -/- mice compared with control mice. In addition, the increase of the inflammatory cytokines (tumor necrosis factor-α and IL-6) in plasma was delayed in CCR1 -/- mice compared with control mice. These data demonstrate that CCR1 participates in cell recruitment to the kidney and amplification of the inflammatory response that contributes to HUS development. Blockade of CCR1 could be important to the design of future therapies to restrain the inflammatory response involved in the development of HUS.
publishDate 2012
dc.date.none.fl_str_mv 2012-03
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/11336/91155
Ramos, Maria Victoria; Auvynet, Constance; Poupel, Lucie; Rodero, Mathieu; Mejias, María Pilar; et al.; Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome; American Society of Investigative Pathology; American Journal Of Pathology; 180; 3; 3-2012; 1040-1048
0002-9440
CONICET Digital
CONICET
url http://hdl.handle.net/11336/91155
identifier_str_mv Ramos, Maria Victoria; Auvynet, Constance; Poupel, Lucie; Rodero, Mathieu; Mejias, María Pilar; et al.; Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome; American Society of Investigative Pathology; American Journal Of Pathology; 180; 3; 3-2012; 1040-1048
0002-9440
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0002944011010741
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ajpath.2011.11.011
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
dc.publisher.none.fl_str_mv American Society of Investigative Pathology
publisher.none.fl_str_mv American Society of Investigative Pathology
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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