Control of infection versus articular damage: role of neutrophils and 5- lipoxygenase in septic arthritis
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Publication Date: | 2017 |
Format: | Doctoral thesis |
Language: | eng |
Source: | Repositório Institucional da UFMG |
Download full: | http://hdl.handle.net/1843/34914 |
Summary: | CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico |
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Flávio Almeida Amaralhttp://lattes.cnpq.br/6879375273660867Paul ProostMauro Martins TeixeiraSofie StruyfAngélica Thomaz VieiraGraciela AndreiFabiana Simão MachadoAdriana Maria Kakchasihttp://lattes.cnpq.br/2103774626130020Daiane Boff2021-02-01T15:18:30Z2021-02-01T15:18:30Z2017-08-21http://hdl.handle.net/1843/34914CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoStaphylococcus aureus is the main pathogen associated with septic arthritis. Upon infection, neutrophils are quickly recruited to the joint by different chemoattractants, such as chemokines and leukotriene B4 (LTB4). Although their excessive accumulation is associated with intense pain and permanent articular damage, neutrophils have an important function in controlling bacterial burden. This work aimed to study the role of chemokines and the enzyme 5-lipoxygenase (5-LO) in the control of infection, hypernociception, and tissue damage in S. aureus-induced septic arthritis in mice. The blockade of the chemokine receptors CXCR1/2 from the beginning of infection decreased neutrophil accumulation in S. aureus-infected joint, contributing to the reduction of articular damage and hypernociception, although it increased the bacterial load. CXCR1/2 was important for the killing of S. aureus by purified human neutrophils. The later start of the treatment did not increase the bacterial load, but only transiently decreased hypernociception and did not improved tissue damage. Using another strategy, we blocked the chemokine binding to glycosaminoglycans (GAGs) by intravenously injection of CXCL9 (74-103). Although this treatment decreased neutrophil accumulation in peptidoglycan- and S. aureus-infected joints, during infection it was not effective to reduce articular damage and hypernociception and increased the bacterial load. In another set of experiments, 5-lipoxygenase (LO)-/- mice had a reduced neutrophil accumulation, joint damage, hypernociception, and bacterial load 7 days after S. aureus injection compared to wild type (WT) mice. At day 4, there were increased numbers of activated cluster of differentiation 11c (CD11c)+ cells and T lymphocytes in the joint and draining lymph node of 5-LO-/- compared to WT mice. At this time point, there was an increase of lipoxin A4 (LXA4)/LTB4 ratio in the joint, two byproducts from 5-LO activity. The blockade of the LXA4 surface receptor, ALX/formyl peptide receptor (FPR)2, in WT mice decreased the bacterial load in infected joints. Corroborating, the injection of LXA4 in 5-LO-/- mice increased the number of recovered bacteria. Interestingly, LXA4-treated human dendritic cells decreased chemotaxis under CCL21 stimulation. In conclusion, the blockade of CXCR1/2, chemokine-GAG binding and LXA4 activity could be useful for the improvement of current treatment of S. aureus-induced arthritis by different mechanisms, but commonly by decreasing neutrophil recruitment.engUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Bioquímica e ImunologiaUFMGBrasilICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIAhttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessArtriteStaphylococcus aureusQuimiocinasAraquidonato 5-lipoxigenaseReceptores de lipoxinasArthritisStaphylococcus aureusChemokines5-lipoxygenaseLipoxin A4Control of infection versus articular damage: role of neutrophils and 5- lipoxygenase in septic arthritisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALthesis final version Daiane Boff.pdfthesis final version Daiane Boff.pdfapplication/pdf3719506https://repositorio.ufmg.br/bitstream/1843/34914/1/thesis%20final%20version%20Daiane%20Boff.pdf8ba6034ec452469a3793d84b511e6bbaMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufmg.br/bitstream/1843/34914/2/license_rdfcfd6801dba008cb6adbd9838b81582abMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82119https://repositorio.ufmg.br/bitstream/1843/34914/3/license.txt34badce4be7e31e3adb4575ae96af679MD531843/349142021-02-01 12:18:30.542oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2021-02-01T15:18:30Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Control of infection versus articular damage: role of neutrophils and 5- lipoxygenase in septic arthritis |
title |
Control of infection versus articular damage: role of neutrophils and 5- lipoxygenase in septic arthritis |
spellingShingle |
Control of infection versus articular damage: role of neutrophils and 5- lipoxygenase in septic arthritis Daiane Boff Arthritis Staphylococcus aureus Chemokines 5-lipoxygenase Lipoxin A4 Artrite Staphylococcus aureus Quimiocinas Araquidonato 5-lipoxigenase Receptores de lipoxinas |
title_short |
Control of infection versus articular damage: role of neutrophils and 5- lipoxygenase in septic arthritis |
title_full |
Control of infection versus articular damage: role of neutrophils and 5- lipoxygenase in septic arthritis |
title_fullStr |
Control of infection versus articular damage: role of neutrophils and 5- lipoxygenase in septic arthritis |
title_full_unstemmed |
Control of infection versus articular damage: role of neutrophils and 5- lipoxygenase in septic arthritis |
title_sort |
Control of infection versus articular damage: role of neutrophils and 5- lipoxygenase in septic arthritis |
author |
Daiane Boff |
author_facet |
Daiane Boff |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Flávio Almeida Amaral |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6879375273660867 |
dc.contributor.advisor2.fl_str_mv |
Paul Proost |
dc.contributor.advisor-co1.fl_str_mv |
Mauro Martins Teixeira |
dc.contributor.advisor-co2.fl_str_mv |
Sofie Struyf |
dc.contributor.referee1.fl_str_mv |
Angélica Thomaz Vieira |
dc.contributor.referee2.fl_str_mv |
Graciela Andrei |
dc.contributor.referee3.fl_str_mv |
Fabiana Simão Machado |
dc.contributor.referee4.fl_str_mv |
Adriana Maria Kakchasi |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2103774626130020 |
dc.contributor.author.fl_str_mv |
Daiane Boff |
contributor_str_mv |
Flávio Almeida Amaral Paul Proost Mauro Martins Teixeira Sofie Struyf Angélica Thomaz Vieira Graciela Andrei Fabiana Simão Machado Adriana Maria Kakchasi |
dc.subject.por.fl_str_mv |
Arthritis Staphylococcus aureus Chemokines 5-lipoxygenase Lipoxin A4 |
topic |
Arthritis Staphylococcus aureus Chemokines 5-lipoxygenase Lipoxin A4 Artrite Staphylococcus aureus Quimiocinas Araquidonato 5-lipoxigenase Receptores de lipoxinas |
dc.subject.other.pt_BR.fl_str_mv |
Artrite Staphylococcus aureus Quimiocinas Araquidonato 5-lipoxigenase Receptores de lipoxinas |
description |
CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017-08-21 |
dc.date.accessioned.fl_str_mv |
2021-02-01T15:18:30Z |
dc.date.available.fl_str_mv |
2021-02-01T15:18:30Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/34914 |
url |
http://hdl.handle.net/1843/34914 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/3.0/pt/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/3.0/pt/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Bioquímica e Imunologia |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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Universidade Federal de Minas Gerais (UFMG) |
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UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG |
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