Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor

Detalhes bibliográficos
Autor(a) principal: Albuquerque, Cassiano Felipe Gonçalves de
Data de Publicação: 2014
Outros Autores: Burth, Patrícia, Silva, Adriana Ribeiro, Moraes, Isabel Matos Medeiros de, Oliveira, Flora Magno de Jesus, Santelli, Ricardo Erthal, Freire, Aline Soares, Lima, Gerson Silva de, Silva, Emilson Domingos da, Silva, Camila Ignácio da, Morandi, Verônica, Bozza, Patricia Torres, Ibrahim, Mauricio Younes, Faria Neto, Hugo Caire de Castro, Faria, Mauro Velho de Castro
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/10545
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
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spelling Albuquerque, Cassiano Felipe Gonçalves deBurth, PatríciaSilva, Adriana RibeiroMoraes, Isabel Matos Medeiros deOliveira, Flora Magno de JesusSantelli, Ricardo ErthalFreire, Aline SoaresLima, Gerson Silva deSilva, Emilson Domingos daSilva, Camila Ignácio daMorandi, VerônicaBozza, Patricia TorresIbrahim, Mauricio YounesFaria Neto, Hugo Caire de CastroFaria, Mauro Velho de Castro2015-05-27T13:39:50Z2015-05-27T13:39:50Z2014ALBUQUERQUE, Cassiano Felippe G. de et al. Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor. Respiratory Research, v.15, n.93, 12p, 2014.1465-9921https://www.arca.fiocruz.br/handle/icict/1054510.1186/s12931-014-0093-2engBioMed CentralMurine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.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.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Departamento de Química Analítica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Departamento de Química Analítica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Bio-Manguinhos. Departamento de Reativos para Diagnóstico. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Bio-Manguinhos. Departamento de Reativos para Diagnóstico. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.Universidade Federal do Rio de Janeiro. Departamento de Química Analítica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Departamento de Medicina Interna. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Departamento de Medicina Interna. Rio de Janeiro, RJ, Brasil.Background Leptospiral glycolipoprotein (GLP) is a potent and specific Na/K-ATPase inhibitor. Severe pulmonary form of leptospirosis is characterized by edema, inflammation and intra-alveolar hemorrhage having a dismal prognosis. Resolution of edema and inflammation determines the outcome of lung injury. Na/K-ATPase activity is responsible for edema clearance. This enzyme works as a cell receptor that triggers activation of mitogen-activated protein kinase (MAPK) intracellular signaling pathway. Therefore, injection of GLP into lungs induces injury by triggering inflammation. Methods We injected GLP and ouabain, into mice lungs and compared their effects. Bronchoalveolar lavage fluid (BALF) was collected for cell and lipid body counting and measurement of protein and lipid mediators (PGE2 and LTB4). The levels of the IL-6, TNFα, IL-1B and MIP-1α were also quantified. Lung images illustrate the injury and whole-body plethysmography was performed to assay lung function. We used Toll-like receptor 4 (TLR4) knockout mice to evaluate leptospiral GLP-induced lung injury. Na/K-ATPase activity was determined in lung cells by nonradioactive rubidium incorporation. We analyzed MAPK p38 activation in lung and in epithelial and endothelial cells. Results Leptospiral GLP and ouabain induced lung edema, cell migration and activation, production of lipid mediators and cytokines and hemorrhage. They induced lung function alterations and inhibited rubidium incorporation. Using TLR4 knockout mice, we showed that the GLP action was not dependent on TLR4 activation. GLP activated of p38 and enhanced cytokine production in cell cultures which was reversed by a selective p38 inhibitor. Conclusions GLP and ouabain induced lung injury, as evidenced by increased lung inflammation and hemorrhage. To our knowledge, this is the first report showing GLP induces lung injury. GLP and ouabain are Na/K-ATPase targets, triggering intracellular signaling pathways. We showed p38 activation by GLP-induced lung injury, which was may be linked to Na/K-ATPase inhibition. Lung inflammation induced by GLP was not dependent on TLR4 activation.Leptospiral GLPNa/K-ATPaseLung injuryToll-like receptorsOuabainMAPK p38Lesão PulmonarOuabaínainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1914https://www.arca.fiocruz.br/bitstream/icict/10545/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALflora_oliveiraetal_IOC_2014.pdfapplication/pdf1180191https://www.arca.fiocruz.br/bitstream/icict/10545/2/flora_oliveiraetal_IOC_2014.pdf3f0e6389d8088afd77cd2f618a728e09MD52TEXTflora_oliveiraetal_IOC_2014.pdf.txtflora_oliveiraetal_IOC_2014.pdf.txtExtracted texttext/plain55911https://www.arca.fiocruz.br/bitstream/icict/10545/3/flora_oliveiraetal_IOC_2014.pdf.txtc41273f2054bab064d2028403874cee2MD53icict/105452022-06-24 12:17:31.767oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T15:17:31Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor
title Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor
spellingShingle Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor
Albuquerque, Cassiano Felipe Gonçalves de
Leptospiral GLP
Na/K-ATPase
Lung injury
Toll-like receptors
Ouabain
MAPK p38
Lesão Pulmonar
Ouabaína
title_short Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor
title_full Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor
title_fullStr Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor
title_full_unstemmed Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor
title_sort Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor
author Albuquerque, Cassiano Felipe Gonçalves de
author_facet Albuquerque, Cassiano Felipe Gonçalves de
Burth, Patrícia
Silva, Adriana Ribeiro
Moraes, Isabel Matos Medeiros de
Oliveira, Flora Magno de Jesus
Santelli, Ricardo Erthal
Freire, Aline Soares
Lima, Gerson Silva de
Silva, Emilson Domingos da
Silva, Camila Ignácio da
Morandi, Verônica
Bozza, Patricia Torres
Ibrahim, Mauricio Younes
Faria Neto, Hugo Caire de Castro
Faria, Mauro Velho de Castro
author_role author
author2 Burth, Patrícia
Silva, Adriana Ribeiro
Moraes, Isabel Matos Medeiros de
Oliveira, Flora Magno de Jesus
Santelli, Ricardo Erthal
Freire, Aline Soares
Lima, Gerson Silva de
Silva, Emilson Domingos da
Silva, Camila Ignácio da
Morandi, Verônica
Bozza, Patricia Torres
Ibrahim, Mauricio Younes
Faria Neto, Hugo Caire de Castro
Faria, Mauro Velho de Castro
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Albuquerque, Cassiano Felipe Gonçalves de
Burth, Patrícia
Silva, Adriana Ribeiro
Moraes, Isabel Matos Medeiros de
Oliveira, Flora Magno de Jesus
Santelli, Ricardo Erthal
Freire, Aline Soares
Lima, Gerson Silva de
Silva, Emilson Domingos da
Silva, Camila Ignácio da
Morandi, Verônica
Bozza, Patricia Torres
Ibrahim, Mauricio Younes
Faria Neto, Hugo Caire de Castro
Faria, Mauro Velho de Castro
dc.subject.en.pt_BR.fl_str_mv Leptospiral GLP
Na/K-ATPase
Lung injury
Toll-like receptors
Ouabain
MAPK p38
topic Leptospiral GLP
Na/K-ATPase
Lung injury
Toll-like receptors
Ouabain
MAPK p38
Lesão Pulmonar
Ouabaína
dc.subject.decs.pt_BR.fl_str_mv Lesão Pulmonar
Ouabaína
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
publishDate 2014
dc.date.issued.fl_str_mv 2014
dc.date.accessioned.fl_str_mv 2015-05-27T13:39:50Z
dc.date.available.fl_str_mv 2015-05-27T13:39:50Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv ALBUQUERQUE, Cassiano Felippe G. de et al. Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor. Respiratory Research, v.15, n.93, 12p, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/10545
dc.identifier.issn.pt_BR.fl_str_mv 1465-9921
dc.identifier.doi.pt_BR.fl_str_mv 10.1186/s12931-014-0093-2
identifier_str_mv ALBUQUERQUE, Cassiano Felippe G. de et al. Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor. Respiratory Research, v.15, n.93, 12p, 2014.
1465-9921
10.1186/s12931-014-0093-2
url https://www.arca.fiocruz.br/handle/icict/10545
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