Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration

Detalhes bibliográficos
Autor(a) principal: Cunha, Mariana G. A. Teixeira da
Data de Publicação: 2013
Outros Autores: Gomes, Rachel N., Roehrs, Nathassia, Bozza, Fernando A., Prescott, Stephen M., Stafforini, Diana, Zimmerman, Guy A., Bozza, Patrícia T., Faria Neto, Hugo C. Castro
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/12598
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
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spelling Cunha, Mariana G. A. Teixeira daGomes, Rachel N.Roehrs, NathassiaBozza, Fernando A.Prescott, Stephen M.Stafforini, DianaZimmerman, Guy A.Bozza, Patrícia T.Faria Neto, Hugo C. Castro2016-01-22T17:06:17Z2016-01-22T17:06:17Z2013CUNHA, Mariana G. A. Teixeira da; Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration. Plos One, v.8, n.9, e74567. 7p, 2013.1932-6203https://www.arca.fiocruz.br/handle/icict/1259810.1371/journal.pone.0074567engPublic Library of ScienceBacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administrationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Investigação em Medicina Intensiva. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Investigação em Medicina Intensiva. Rio de Janeiro, RJ, BrasilOklahoma Medical Research Foundation. Oklahoma City, USA.Huntsman Cancer Institute. Salt Lake City, Utah, USA.University of Utah. Program in Human Molecular Biology and Genetics. Salt Lake City, Utah, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Current evidence indicates that dysregulation of the host inflammatory response to infectious agents is central to the mortality of patients with sepsis. Strategies to block inflammatory mediators such as PAF have been investigated as adjuvant therapies for sepsis. PAF-AH, the enzyme responsible for PAF degradation, showed positive results in pre-clinical studies and phase II clinical trials, but the results of a phase III study were disappointing. In this study, we investigated the potential protective mechanism of PAF-AH in sepsis using the murine model of cecal ligation and puncture (CLP). Treatment with rPAF-AH increased peritoneal fluid levels of the anti-inflammatory mediators MCP-1/CCL2 after CLP. The numbers of bacteria (CFU) in the peritoneal cavity were decreased in the rPAF-AH-treated group, indicating more efficient bacterial clearance after rPAF-AH treatment. Interestingly, we observed increased levels of nitric oxide (NO) after PAF-AH administration, and rPAF-AH treatment did not decrease CFU numbers either in iNOS-deficient mice or in CCR2-deficient mice. We concluded that administration of exogenous rPAF-AH reduced inflammatory injury, altered cytokine levels and favored bacterial clearance with a clear impact on mortality through modulation of MCP-1/CCL2 and NO levels in a clinically relevant sepsis model.Platelet-Activating Factor-Acetylhydrolase (PAF-AH)SepsisSepseinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/12598/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALmariana_cunha_etal_IOC_2013.pdfmariana_cunha_etal_IOC_2013.pdfapplication/pdf372931https://www.arca.fiocruz.br/bitstream/icict/12598/2/mariana_cunha_etal_IOC_2013.pdfa0f16ff6e7e6a14b1b200ed3a86cb61eMD52TEXTmariana_cunha_etal_IOC_2013.pdf.txtmariana_cunha_etal_IOC_2013.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration
title Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration
spellingShingle Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration
Cunha, Mariana G. A. Teixeira da
Platelet-Activating Factor-Acetylhydrolase (PAF-AH)
Sepsis
Sepse
title_short Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration
title_full Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration
title_fullStr Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration
title_full_unstemmed Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration
title_sort Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration
author Cunha, Mariana G. A. Teixeira da
author_facet Cunha, Mariana G. A. Teixeira da
Gomes, Rachel N.
Roehrs, Nathassia
Bozza, Fernando A.
Prescott, Stephen M.
Stafforini, Diana
Zimmerman, Guy A.
Bozza, Patrícia T.
Faria Neto, Hugo C. Castro
author_role author
author2 Gomes, Rachel N.
Roehrs, Nathassia
Bozza, Fernando A.
Prescott, Stephen M.
Stafforini, Diana
Zimmerman, Guy A.
Bozza, Patrícia T.
Faria Neto, Hugo C. Castro
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Cunha, Mariana G. A. Teixeira da
Gomes, Rachel N.
Roehrs, Nathassia
Bozza, Fernando A.
Prescott, Stephen M.
Stafforini, Diana
Zimmerman, Guy A.
Bozza, Patrícia T.
Faria Neto, Hugo C. Castro
dc.subject.en.pt_BR.fl_str_mv Platelet-Activating Factor-Acetylhydrolase (PAF-AH)
Sepsis
topic Platelet-Activating Factor-Acetylhydrolase (PAF-AH)
Sepsis
Sepse
dc.subject.decs.pt_BR.fl_str_mv Sepse
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2016-01-22T17:06:17Z
dc.date.available.fl_str_mv 2016-01-22T17:06:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.citation.fl_str_mv CUNHA, Mariana G. A. Teixeira da; Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration. Plos One, v.8, n.9, e74567. 7p, 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/12598
dc.identifier.issn.none.fl_str_mv 1932-6203
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pone.0074567
identifier_str_mv CUNHA, Mariana G. A. Teixeira da; Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration. Plos One, v.8, n.9, e74567. 7p, 2013.
1932-6203
10.1371/journal.pone.0074567
url https://www.arca.fiocruz.br/handle/icict/12598
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language eng
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