A central role for free heme in the pathogenesis of severe sepsis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2010 |
| Outros Autores: | , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.1126/scitranslmed.3001118 |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/38710 |
Resumo: | 2020-06-19 |
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Larsen, RasmusGozzelino, RaffaellaJeney, ViktóriaTokaji, LászlóBozza, Fernando A.Japiassú, André M.Bonaparte, DoloresCavalcante, Moisés MarinhoChora, ÂngeloFerreira, AnaMarguti, IvoCardoso, SílviaSepúlveda, NunoSmith, AnnSoares, Miguel P.2019-12-19T14:36:00Z2019-12-19T14:36:00Z2010LARSEN, Rasmus et al. A central role for free heme in the pathogenesis of severe sepsis. Science Translational Medicine, v. 2, n. 51, p. 1-12, Sept. 2010.1946-6234https://www.arca.fiocruz.br/handle/icict/3871010.1126/scitranslmed.30011181946-6242engAmerican Association for the Advancement of ScienceA central role for free heme in the pathogenesis of severe sepsisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2020-06-19Instituto Gulbenkian de Ciência. Oeiras, Portugal.Instituto Gulbenkian de Ciência. Oeiras, Portugal.Instituto Gulbenkian de Ciência. Oeiras, Portugal.Instituto Gulbenkian de Ciência. Oeiras, Portugal.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Unidade de Terapia Intensiva. Rio de Janeiro, RJ, Brasil / D’Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Unidade de Terapia Intensiva. Rio de Janeiro, RJ, Brasil / D’Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.Instituto Gulbenkian de Ciência. Oeiras, Portugal.Instituto Gulbenkian de Ciência. Oeiras, Portugal.Instituto Gulbenkian de Ciência. Oeiras, Portugal.Instituto Gulbenkian de Ciência. Oeiras, Portugal.Instituto Gulbenkian de Ciência. Oeiras, Portugal.Instituto Gulbenkian de Ciência. Oeiras, Portugal.Instituto Gulbenkian de Ciência. Oeiras, Portugal / University of Lisbon. Center of Statistics and Applications. Lisbon, Portugal.University of Missouri. Division of Molecular Biology and Biochemistry. Kansas City, MO, USA.Instituto Gulbenkian de Ciência. Oeiras, Portugal.Low-grade polymicrobial infection induced by cecal ligation and puncture is lethal in heme oxygenase-1–deficient mice (Hmox1−/−), but not in wild-type (Hmox1+/+) mice. Here we demonstrate that the protective effect of this hemecatabolizing enzyme relies on its ability to prevent tissue damage caused by the circulating free heme released from hemoglobin during infection. Heme administration after low-grade infection in mice promoted tissue damage and severe sepsis. Free heme contributed to the pathogenesis of severe sepsis irrespective of pathogen load, revealing that it compromised host tolerance to infection. Development of lethal forms of severe sepsis after high-grade infection was associated with reduced serum concentrations of the heme sequestering protein hemopexin (HPX), whereas HPX administration after high-grade infection prevented tissue damage and lethality. Finally, the lethal outcome of septic shock in patients was also associated with reduced HPX serum concentrations. We propose that targeting free heme by HPX might be used therapeutically to treat severe sepsis.Free hemeSepsisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/38710/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALve_Larsen_Rasmus_etal_INI_2010.pdfve_Larsen_Rasmus_etal_INI_2010.pdfapplication/pdf1898791https://www.arca.fiocruz.br/bitstream/icict/38710/2/ve_Larsen_Rasmus_etal_INI_2010.pdfc524803cbec7bde920de9e78b6c5a9d8MD52TEXTve_Larsen_Rasmus_etal_INI_2010.pdf.txtve_Larsen_Rasmus_etal_INI_2010.pdf.txtExtracted texttext/plain77446https://www.arca.fiocruz.br/bitstream/icict/38710/3/ve_Larsen_Rasmus_etal_INI_2010.pdf.txt0af6159f990c781ee669f7f6c8eaaddeMD53icict/387102021-03-24 16:32:33.184oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352021-03-24T19:32:33Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
A central role for free heme in the pathogenesis of severe sepsis |
| title |
A central role for free heme in the pathogenesis of severe sepsis |
| spellingShingle |
A central role for free heme in the pathogenesis of severe sepsis Larsen, Rasmus Free heme Sepsis |
| title_short |
A central role for free heme in the pathogenesis of severe sepsis |
| title_full |
A central role for free heme in the pathogenesis of severe sepsis |
| title_fullStr |
A central role for free heme in the pathogenesis of severe sepsis |
| title_full_unstemmed |
A central role for free heme in the pathogenesis of severe sepsis |
| title_sort |
A central role for free heme in the pathogenesis of severe sepsis |
| author |
Larsen, Rasmus |
| author_facet |
Larsen, Rasmus Gozzelino, Raffaella Jeney, Viktória Tokaji, László Bozza, Fernando A. Japiassú, André M. Bonaparte, Dolores Cavalcante, Moisés Marinho Chora, Ângelo Ferreira, Ana Marguti, Ivo Cardoso, Sílvia Sepúlveda, Nuno Smith, Ann Soares, Miguel P. |
| author_role |
author |
| author2 |
Gozzelino, Raffaella Jeney, Viktória Tokaji, László Bozza, Fernando A. Japiassú, André M. Bonaparte, Dolores Cavalcante, Moisés Marinho Chora, Ângelo Ferreira, Ana Marguti, Ivo Cardoso, Sílvia Sepúlveda, Nuno Smith, Ann Soares, Miguel P. |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Larsen, Rasmus Gozzelino, Raffaella Jeney, Viktória Tokaji, László Bozza, Fernando A. Japiassú, André M. Bonaparte, Dolores Cavalcante, Moisés Marinho Chora, Ângelo Ferreira, Ana Marguti, Ivo Cardoso, Sílvia Sepúlveda, Nuno Smith, Ann Soares, Miguel P. |
| dc.subject.en.pt_BR.fl_str_mv |
Free heme Sepsis |
| topic |
Free heme Sepsis |
| description |
2020-06-19 |
| publishDate |
2010 |
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2010 |
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2019-12-19T14:36:00Z |
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2019-12-19T14:36:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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LARSEN, Rasmus et al. A central role for free heme in the pathogenesis of severe sepsis. Science Translational Medicine, v. 2, n. 51, p. 1-12, Sept. 2010. |
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https://www.arca.fiocruz.br/handle/icict/38710 |
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1946-6234 |
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10.1126/scitranslmed.3001118 |
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1946-6242 |
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LARSEN, Rasmus et al. A central role for free heme in the pathogenesis of severe sepsis. Science Translational Medicine, v. 2, n. 51, p. 1-12, Sept. 2010. 1946-6234 10.1126/scitranslmed.3001118 1946-6242 |
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American Association for the Advancement of Science |
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American Association for the Advancement of Science |
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