Osteopontin is upregulated in human and murine acute schistosomiasis mansoni
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | http://hdl.handle.net/1843/40447 |
Resumo: | Background Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection. Methodology/Principal Findings Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7–11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells. Conclusions/Significance S. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease. |
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2022-03-24T20:35:37Z2022-03-24T20:35:37Z2016101010.1371/journal.pntd.00050571935-2735http://hdl.handle.net/1843/40447Background Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection. Methodology/Principal Findings Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7–11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells. Conclusions/Significance S. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease.Fundo A esquistossomose mansônica aguda sintomática é uma reação de hipersensibilidade sistêmica contra o esquistossomose migratório e ovos maduros após uma infecção primária. Os mecanismos envolvidos na patogênese da esquistossomose aguda não estão totalmente elucidados. A osteopontina tem sido implicada em reações granulomatosas e em lesão hepática aguda. Nossos objetivos foram avaliar se a osteopontina desempenha um papel na infecção aguda por Schistosoma mansoni em camundongos humanos e experimentalmente infectados e se os níveis circulantes de OPN podem ser um novo biomarcador dessa infecção. Metodologia/Constatações Principais Os níveis séricos/plasmáticos de osteopontina foram medidos por ELISA em pacientes com esquistossomose aguda (n = 28), hepatointestinal (n = 26), hepatoesplênica (n = 39) e em controles não infectados (n = 21). A osteopontina hepática foi avaliada por imuno-histoquímica em biópsias por agulha de 5 pacientes. Soros e osteopontina hepática foram quantificados no modelo murino de esquistossomose mansônica durante a fase aguda (7 e 8 semanas pós infecção, n = 10) e crônica (30 semanas pós infecção, n = 8). Os níveis circulantes de osteopontina estão aumentados em pacientes com esquistossomose aguda (p = 0,0001). Os níveis mais altos de OPN foram observados durante o pico dos sintomas clínicos (7 a 11 semanas após a infecção), retornando ao nível basal assim que os granulomas foram modulados (> 12 semanas após a infecção). Os níveis plasmáticos na esquistossomose aguda foram ainda maiores do que em pacientes hepatoesplênicos. O modelo murino espelhava a doença humana. Os macrófagos foram a principal fonte de OPN na esquistossomose aguda humana e murina, enquanto a reação ductular mantém a produção de OPN na doença hepatoesplênica. Antígenos solúveis de ovos de S. mansoni induziram a expressão de OPN em células kupffer humanas primárias. Conclusões/Significação Antígenos de ovos de S. mansoni induzem a produção de OPN por macrófagos nos granulomas necrótico-exsudativos característicos da esquistossomose mansônica aguda. Os níveis circulantes de OPN são regulados positivamente na esquistossomose aguda humana e murina e podem ser um biomarcador não invasivo dessa forma de doença.engUniversidade Federal de Minas GeraisUFMGBrasilMED - DEPARTAMENTO DE CLÍNICA MÉDICAPlos neglected tropical diseasesEsquistossomoseEsquistossomose hepatoesplênicaFibrose hepáticaSchistosomiasisAcute schistosomiasisHepatosplenic schistosomiasisLiver fibrosisOsteopontinOsteopontin is upregulated in human and murine acute schistosomiasis mansoniA osteopontina é regulada positivamente na esquistossomose mansônica aguda humana e murinainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005057Thiago AlmeidapereiraRafal p WitekWilliam Evan SecorFausto Edmundo Lima PereiraJose Roberto LambertucciAnna Mae DiehlWing-kin SynFrederico Figueiredo AmâncioPedro Henrique Diniz CunhaJulia Fonseca Morais CaporaliGuilherme Vaz de Melo TrindadeElisângela Trindade SantosMárcia Maria SouzaZilton Araújo Andradeapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINAL2016_Osteopontin is upregulated in human and murine acute schistosomiasis mansoni.pdf2016_Osteopontin is upregulated in human and murine acute schistosomiasis mansoni.pdfapplication/pdf1871415https://repositorio.ufmg.br/bitstream/1843/40447/2/2016_Osteopontin%20is%20upregulated%20in%20human%20and%20murine%20acute%20schistosomiasis%20mansoni.pdf902bd6813c234ec97dbb888b075e72d1MD52LICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/40447/1/License.txtfa505098d172de0bc8864fc1287ffe22MD511843/404472022-03-24 17:35:38.734oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2022-03-24T20:35:38Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Osteopontin is upregulated in human and murine acute schistosomiasis mansoni |
dc.title.alternative.pt_BR.fl_str_mv |
A osteopontina é regulada positivamente na esquistossomose mansônica aguda humana e murina |
title |
Osteopontin is upregulated in human and murine acute schistosomiasis mansoni |
spellingShingle |
Osteopontin is upregulated in human and murine acute schistosomiasis mansoni Thiago Almeidapereira Schistosomiasis Acute schistosomiasis Hepatosplenic schistosomiasis Liver fibrosis Osteopontin Esquistossomose Esquistossomose hepatoesplênica Fibrose hepática |
title_short |
Osteopontin is upregulated in human and murine acute schistosomiasis mansoni |
title_full |
Osteopontin is upregulated in human and murine acute schistosomiasis mansoni |
title_fullStr |
Osteopontin is upregulated in human and murine acute schistosomiasis mansoni |
title_full_unstemmed |
Osteopontin is upregulated in human and murine acute schistosomiasis mansoni |
title_sort |
Osteopontin is upregulated in human and murine acute schistosomiasis mansoni |
author |
Thiago Almeidapereira |
author_facet |
Thiago Almeidapereira Rafal p Witek William Evan Secor Fausto Edmundo Lima Pereira Jose Roberto Lambertucci Anna Mae Diehl Wing-kin Syn Frederico Figueiredo Amâncio Pedro Henrique Diniz Cunha Julia Fonseca Morais Caporali Guilherme Vaz de Melo Trindade Elisângela Trindade Santos Márcia Maria Souza Zilton Araújo Andrade |
author_role |
author |
author2 |
Rafal p Witek William Evan Secor Fausto Edmundo Lima Pereira Jose Roberto Lambertucci Anna Mae Diehl Wing-kin Syn Frederico Figueiredo Amâncio Pedro Henrique Diniz Cunha Julia Fonseca Morais Caporali Guilherme Vaz de Melo Trindade Elisângela Trindade Santos Márcia Maria Souza Zilton Araújo Andrade |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Thiago Almeidapereira Rafal p Witek William Evan Secor Fausto Edmundo Lima Pereira Jose Roberto Lambertucci Anna Mae Diehl Wing-kin Syn Frederico Figueiredo Amâncio Pedro Henrique Diniz Cunha Julia Fonseca Morais Caporali Guilherme Vaz de Melo Trindade Elisângela Trindade Santos Márcia Maria Souza Zilton Araújo Andrade |
dc.subject.por.fl_str_mv |
Schistosomiasis Acute schistosomiasis Hepatosplenic schistosomiasis Liver fibrosis Osteopontin |
topic |
Schistosomiasis Acute schistosomiasis Hepatosplenic schistosomiasis Liver fibrosis Osteopontin Esquistossomose Esquistossomose hepatoesplênica Fibrose hepática |
dc.subject.other.pt_BR.fl_str_mv |
Esquistossomose Esquistossomose hepatoesplênica Fibrose hepática |
description |
Background Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection. Methodology/Principal Findings Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7–11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells. Conclusions/Significance S. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016 |
dc.date.accessioned.fl_str_mv |
2022-03-24T20:35:37Z |
dc.date.available.fl_str_mv |
2022-03-24T20:35:37Z |
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.uri.fl_str_mv |
http://hdl.handle.net/1843/40447 |
dc.identifier.doi.pt_BR.fl_str_mv |
10.1371/journal.pntd.0005057 |
dc.identifier.issn.pt_BR.fl_str_mv |
1935-2735 |
identifier_str_mv |
10.1371/journal.pntd.0005057 1935-2735 |
url |
http://hdl.handle.net/1843/40447 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Plos neglected tropical diseases |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
MED - DEPARTAMENTO DE CLÍNICA MÉDICA |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
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