Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/5906 http://dx.doi.org/10.1590/S0100-879X2010007500081 |
Resumo: | Tolerance to lipopolysaccharide (LPS) occurs when animals or cells exposed to LPS become hyporesponsive to a subsequent challenge with LPS. This mechanism is believed to be involved in the down-regulation of cellular responses observed in septic patients. The aim of this investigation was to evaluate LPS-induced monocyte tolerance of healthy volunteers using whole blood. The detection of intracellular IL-6, bacterial phagocytosis and reactive oxygen species (ROS) was determined by flow cytometry, using anti-IL-6-PE, heat-killed Staphylococcus aureus stained with propidium iodide and 2',7'-dichlorofluorescein diacetate, respectively. Monocytes were gated in whole blood by combining FSC and SSC parameters and CD14-positive staining. The exposure to increasing LPS concentrations resulted in lower intracellular concentration of IL-6 in monocytes after challenge. A similar effect was observed with challenge with MALP-2 (a Toll-like receptor (TLR)2/6 agonist) and killed Pseudomonas aeruginosa and S. aureus, but not with flagellin (a TLR5 agonist). LPS conditioning with 15 ng/mL resulted in a 40% reduction of IL-6 in monocytes. In contrast, phagocytosis of P. aeruginosa and S. aureus and induced ROS generation were preserved or increased in tolerant cells. The phenomenon of tolerance involves a complex regulation in which the production of IL-6 was diminished, whereas the bacterial phagocytosis and production of ROS was preserved. Decreased production of proinflammatory cytokines and preserved or increased production of ROS may be an adaptation to control the deleterious effects of inflammation while preserving antimicrobial activity. |
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Fernandes, Maria da Luz [UNIFESP]Mendes, Marialice Erdelyi [UNIFESP]Brunialti, Milena Karina Coló [UNIFESP]Salomão, Reinaldo [UNIFESP]Universidade Federal de São Paulo (UNIFESP)2015-06-14T13:41:51Z2015-06-14T13:41:51Z2010-09-01Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 43, n. 9, p. 860-868, 2010.0100-879Xhttp://repositorio.unifesp.br/handle/11600/5906http://dx.doi.org/10.1590/S0100-879X2010007500081S0100-879X2010000900008.pdfS0100-879X201000090000810.1590/S0100-879X2010007500081WOS:000283262800008Tolerance to lipopolysaccharide (LPS) occurs when animals or cells exposed to LPS become hyporesponsive to a subsequent challenge with LPS. This mechanism is believed to be involved in the down-regulation of cellular responses observed in septic patients. The aim of this investigation was to evaluate LPS-induced monocyte tolerance of healthy volunteers using whole blood. The detection of intracellular IL-6, bacterial phagocytosis and reactive oxygen species (ROS) was determined by flow cytometry, using anti-IL-6-PE, heat-killed Staphylococcus aureus stained with propidium iodide and 2',7'-dichlorofluorescein diacetate, respectively. Monocytes were gated in whole blood by combining FSC and SSC parameters and CD14-positive staining. The exposure to increasing LPS concentrations resulted in lower intracellular concentration of IL-6 in monocytes after challenge. A similar effect was observed with challenge with MALP-2 (a Toll-like receptor (TLR)2/6 agonist) and killed Pseudomonas aeruginosa and S. aureus, but not with flagellin (a TLR5 agonist). LPS conditioning with 15 ng/mL resulted in a 40% reduction of IL-6 in monocytes. In contrast, phagocytosis of P. aeruginosa and S. aureus and induced ROS generation were preserved or increased in tolerant cells. The phenomenon of tolerance involves a complex regulation in which the production of IL-6 was diminished, whereas the bacterial phagocytosis and production of ROS was preserved. Decreased production of proinflammatory cytokines and preserved or increased production of ROS may be an adaptation to control the deleterious effects of inflammation while preserving antimicrobial activity.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Divisão de Moléstias InfecciosasUNIFESP, EPM, Divisão de Moléstias InfecciosasFAPESP: 2006/58744-1SciELO860-868engAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological ResearchIL-6ROSPhagocytosisMALP-2FlagellinLPS toleranceHuman monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen speciesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALS0100-879X2010000900008.pdfapplication/pdf884369${dspace.ui.url}/bitstream/11600/5906/1/S0100-879X2010000900008.pdf2edabc6ade70553abd15aca641dde78fMD51open accessTEXTS0100-879X2010000900008.pdf.txtS0100-879X2010000900008.pdf.txtExtracted texttext/plain37433${dspace.ui.url}/bitstream/11600/5906/2/S0100-879X2010000900008.pdf.txt0d114ec2678c26130a803d26b8fccc91MD52open access11600/59062022-07-08 10:54:10.132open accessoai:repositorio.unifesp.br:11600/5906Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-07-08T13:54:10Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species |
title |
Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species |
spellingShingle |
Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species Fernandes, Maria da Luz [UNIFESP] IL-6 ROS Phagocytosis MALP-2 Flagellin LPS tolerance |
title_short |
Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species |
title_full |
Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species |
title_fullStr |
Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species |
title_full_unstemmed |
Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species |
title_sort |
Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species |
author |
Fernandes, Maria da Luz [UNIFESP] |
author_facet |
Fernandes, Maria da Luz [UNIFESP] Mendes, Marialice Erdelyi [UNIFESP] Brunialti, Milena Karina Coló [UNIFESP] Salomão, Reinaldo [UNIFESP] |
author_role |
author |
author2 |
Mendes, Marialice Erdelyi [UNIFESP] Brunialti, Milena Karina Coló [UNIFESP] Salomão, Reinaldo [UNIFESP] |
author2_role |
author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Fernandes, Maria da Luz [UNIFESP] Mendes, Marialice Erdelyi [UNIFESP] Brunialti, Milena Karina Coló [UNIFESP] Salomão, Reinaldo [UNIFESP] |
dc.subject.eng.fl_str_mv |
IL-6 ROS Phagocytosis MALP-2 Flagellin LPS tolerance |
topic |
IL-6 ROS Phagocytosis MALP-2 Flagellin LPS tolerance |
description |
Tolerance to lipopolysaccharide (LPS) occurs when animals or cells exposed to LPS become hyporesponsive to a subsequent challenge with LPS. This mechanism is believed to be involved in the down-regulation of cellular responses observed in septic patients. The aim of this investigation was to evaluate LPS-induced monocyte tolerance of healthy volunteers using whole blood. The detection of intracellular IL-6, bacterial phagocytosis and reactive oxygen species (ROS) was determined by flow cytometry, using anti-IL-6-PE, heat-killed Staphylococcus aureus stained with propidium iodide and 2',7'-dichlorofluorescein diacetate, respectively. Monocytes were gated in whole blood by combining FSC and SSC parameters and CD14-positive staining. The exposure to increasing LPS concentrations resulted in lower intracellular concentration of IL-6 in monocytes after challenge. A similar effect was observed with challenge with MALP-2 (a Toll-like receptor (TLR)2/6 agonist) and killed Pseudomonas aeruginosa and S. aureus, but not with flagellin (a TLR5 agonist). LPS conditioning with 15 ng/mL resulted in a 40% reduction of IL-6 in monocytes. In contrast, phagocytosis of P. aeruginosa and S. aureus and induced ROS generation were preserved or increased in tolerant cells. The phenomenon of tolerance involves a complex regulation in which the production of IL-6 was diminished, whereas the bacterial phagocytosis and production of ROS was preserved. Decreased production of proinflammatory cytokines and preserved or increased production of ROS may be an adaptation to control the deleterious effects of inflammation while preserving antimicrobial activity. |
publishDate |
2010 |
dc.date.issued.fl_str_mv |
2010-09-01 |
dc.date.accessioned.fl_str_mv |
2015-06-14T13:41:51Z |
dc.date.available.fl_str_mv |
2015-06-14T13:41:51Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 43, n. 9, p. 860-868, 2010. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/5906 http://dx.doi.org/10.1590/S0100-879X2010007500081 |
dc.identifier.issn.none.fl_str_mv |
0100-879X |
dc.identifier.file.none.fl_str_mv |
S0100-879X2010000900008.pdf |
dc.identifier.scielo.none.fl_str_mv |
S0100-879X2010000900008 |
dc.identifier.doi.none.fl_str_mv |
10.1590/S0100-879X2010007500081 |
dc.identifier.wos.none.fl_str_mv |
WOS:000283262800008 |
identifier_str_mv |
Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 43, n. 9, p. 860-868, 2010. 0100-879X S0100-879X2010000900008.pdf S0100-879X2010000900008 10.1590/S0100-879X2010007500081 WOS:000283262800008 |
url |
http://repositorio.unifesp.br/handle/11600/5906 http://dx.doi.org/10.1590/S0100-879X2010007500081 |
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eng |
language |
eng |
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Brazilian Journal of Medical and Biological Research |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
860-868 |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
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Associação Brasileira de Divulgação Científica |
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