Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor

Autores
Grewal, Prabhjit K.; Aziz, Peter V.; Uchiyama, Satoshi; Rubio, Gabriel R.; Lardone, Ricardo Dante; Le, Dzung; Varki, Nissi M.; Nizet, Victor; Marth, Jamey D.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The endocytic Ashwell-Morell receptor (AMR) of hepatocytes detects pathogen remodeling of host glycoproteins by neuraminidase in the bloodstream and mitigates the lethal coagulopathy of sepsis. We have investigated the mechanism of host protection by the AMR during the onset of sepsis and in response to the desialylation of blood glycoproteins by the NanA neuraminidase of Streptococcus pneumoniae. We find that the AMR selects among potential glycoprotein ligands unmasked by microbial neuraminidase activity in pneumococcal sepsis to eliminate from blood circulation host factors that contribute to coagulation and thrombosis. This protection is attributable in large part to the rapid induction of a moderate thrombocytopenia by the AMR. We further show that neuraminidase activity in the blood can be manipulated to induce the clearance of AMR ligands including platelets, thereby preactivating a protective response in pneumococcal sepsis that moderates the severity of disseminated intravascular coagulation and enables host survival.
Fil: Grewal, Prabhjit K.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos
Fil: Aziz, Peter V.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos
Fil: Uchiyama, Satoshi. University of California at San Diego; Estados Unidos
Fil: Rubio, Gabriel R.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos
Fil: Lardone, Ricardo Dante. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Le, Dzung. University of California at San Diego; Estados Unidos
Fil: Varki, Nissi M.. University of California at San Diego; Estados Unidos
Fil: Nizet, Victor. University of California at San Diego; Estados Unidos
Fil: Marth, Jamey D.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos
Materia
Glycosyation
Coagulopathy
Sepsis
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:11336/26107
Acceder
id CONICETDig_ac166b833402eed12530562296a48761
oai_identifier_str oai:ri.conicet.gov.ar:11336/26107
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptorGrewal, Prabhjit K.Aziz, Peter V.Uchiyama, SatoshiRubio, Gabriel R.Lardone, Ricardo DanteLe, DzungVarki, Nissi M.Nizet, VictorMarth, Jamey D.GlycosyationCoagulopathySepsishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The endocytic Ashwell-Morell receptor (AMR) of hepatocytes detects pathogen remodeling of host glycoproteins by neuraminidase in the bloodstream and mitigates the lethal coagulopathy of sepsis. We have investigated the mechanism of host protection by the AMR during the onset of sepsis and in response to the desialylation of blood glycoproteins by the NanA neuraminidase of Streptococcus pneumoniae. We find that the AMR selects among potential glycoprotein ligands unmasked by microbial neuraminidase activity in pneumococcal sepsis to eliminate from blood circulation host factors that contribute to coagulation and thrombosis. This protection is attributable in large part to the rapid induction of a moderate thrombocytopenia by the AMR. We further show that neuraminidase activity in the blood can be manipulated to induce the clearance of AMR ligands including platelets, thereby preactivating a protective response in pneumococcal sepsis that moderates the severity of disseminated intravascular coagulation and enables host survival.Fil: Grewal, Prabhjit K.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados UnidosFil: Aziz, Peter V.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados UnidosFil: Uchiyama, Satoshi. University of California at San Diego; Estados UnidosFil: Rubio, Gabriel R.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados UnidosFil: Lardone, Ricardo Dante. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Le, Dzung. University of California at San Diego; Estados UnidosFil: Varki, Nissi M.. University of California at San Diego; Estados UnidosFil: Nizet, Victor. University of California at San Diego; Estados UnidosFil: Marth, Jamey D.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados UnidosNational Academy of Sciences2013-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/26107Grewal, Prabhjit K.; Aziz, Peter V.; Uchiyama, Satoshi; Rubio, Gabriel R.; Lardone, Ricardo Dante; et al.; Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 110; 50; 12-2013; 20218-202230027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1313905110info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/110/50/20218info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864324/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-01-08T12:46:12Zoai:ri.conicet.gov.ar:11336/26107instacron: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:34982026-01-08 12:46:12.314CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor
title Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor
spellingShingle Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor
Grewal, Prabhjit K.
Glycosyation
Coagulopathy
Sepsis
title_short Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor
title_full Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor
title_fullStr Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor
title_full_unstemmed Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor
title_sort Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor
dc.creator.none.fl_str_mv Grewal, Prabhjit K.
Aziz, Peter V.
Uchiyama, Satoshi
Rubio, Gabriel R.
Lardone, Ricardo Dante
Le, Dzung
Varki, Nissi M.
Nizet, Victor
Marth, Jamey D.
author Grewal, Prabhjit K.
author_facet Grewal, Prabhjit K.
Aziz, Peter V.
Uchiyama, Satoshi
Rubio, Gabriel R.
Lardone, Ricardo Dante
Le, Dzung
Varki, Nissi M.
Nizet, Victor
Marth, Jamey D.
author_role author
author2 Aziz, Peter V.
Uchiyama, Satoshi
Rubio, Gabriel R.
Lardone, Ricardo Dante
Le, Dzung
Varki, Nissi M.
Nizet, Victor
Marth, Jamey D.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Glycosyation
Coagulopathy
Sepsis
topic Glycosyation
Coagulopathy
Sepsis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The endocytic Ashwell-Morell receptor (AMR) of hepatocytes detects pathogen remodeling of host glycoproteins by neuraminidase in the bloodstream and mitigates the lethal coagulopathy of sepsis. We have investigated the mechanism of host protection by the AMR during the onset of sepsis and in response to the desialylation of blood glycoproteins by the NanA neuraminidase of Streptococcus pneumoniae. We find that the AMR selects among potential glycoprotein ligands unmasked by microbial neuraminidase activity in pneumococcal sepsis to eliminate from blood circulation host factors that contribute to coagulation and thrombosis. This protection is attributable in large part to the rapid induction of a moderate thrombocytopenia by the AMR. We further show that neuraminidase activity in the blood can be manipulated to induce the clearance of AMR ligands including platelets, thereby preactivating a protective response in pneumococcal sepsis that moderates the severity of disseminated intravascular coagulation and enables host survival.
Fil: Grewal, Prabhjit K.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos
Fil: Aziz, Peter V.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos
Fil: Uchiyama, Satoshi. University of California at San Diego; Estados Unidos
Fil: Rubio, Gabriel R.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos
Fil: Lardone, Ricardo Dante. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Le, Dzung. University of California at San Diego; Estados Unidos
Fil: Varki, Nissi M.. University of California at San Diego; Estados Unidos
Fil: Nizet, Victor. University of California at San Diego; Estados Unidos
Fil: Marth, Jamey D.. University of California; Estados Unidos. Sanford-burnham Medical Research Institute; Estados Unidos
description The endocytic Ashwell-Morell receptor (AMR) of hepatocytes detects pathogen remodeling of host glycoproteins by neuraminidase in the bloodstream and mitigates the lethal coagulopathy of sepsis. We have investigated the mechanism of host protection by the AMR during the onset of sepsis and in response to the desialylation of blood glycoproteins by the NanA neuraminidase of Streptococcus pneumoniae. We find that the AMR selects among potential glycoprotein ligands unmasked by microbial neuraminidase activity in pneumococcal sepsis to eliminate from blood circulation host factors that contribute to coagulation and thrombosis. This protection is attributable in large part to the rapid induction of a moderate thrombocytopenia by the AMR. We further show that neuraminidase activity in the blood can be manipulated to induce the clearance of AMR ligands including platelets, thereby preactivating a protective response in pneumococcal sepsis that moderates the severity of disseminated intravascular coagulation and enables host survival.
publishDate 2013
dc.date.none.fl_str_mv 2013-12
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/11336/26107
Grewal, Prabhjit K.; Aziz, Peter V.; Uchiyama, Satoshi; Rubio, Gabriel R.; Lardone, Ricardo Dante; et al.; Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 110; 50; 12-2013; 20218-20223
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/26107
identifier_str_mv Grewal, Prabhjit K.; Aziz, Peter V.; Uchiyama, Satoshi; Rubio, Gabriel R.; Lardone, Ricardo Dante; et al.; Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 110; 50; 12-2013; 20218-20223
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1313905110
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/110/50/20218
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864324/
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 National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
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
_version_ 1853774974960009216
score 13.25844

Publicaciones similares